We demonstrate novel polarization management devices in a custom-designed silicon nitride (Si(3)N(4)) on silicon-on-insulator (SOI) integrated photonics platform. In the platform, Si(3)N(4) waveguides are defined atop silicon waveguides. A broadband polarization rotator-splitter using a TM0-TE1 mode converter in a composite Si(3)N(4)-silicon waveguide is demonstrated. The polarization crosstalk, insertion loss, and polarization dependent loss are less than -19 dB, 1.5 dB, and 1.0 dB, respectively, over a bandwidth of 80 nm. A polarization controller composed of polarization rotator-splitters, multimode interference couplers, and thin film heaters is also demonstrated.
We propose and experimentally demonstrate fiber-to-chip grating couplers with aligned silicon nitride (Si(3)N(4)) and silicon (Si) grating teeth for wide bandwidths and high coupling efficiencies without the use of bottom reflectors. The measured 1-dB bandwidth is a record 80 nm, and the measured peak coupling efficiency is -1.3 dB, which is competitive with the best Si-only grating couplers. The grating couplers are integrated in a Si(3)N(4) on silicon-on-insulator (SOI) integrated optics platform with aligned waveguides in both the Si(3)N(4) and Si, and we demonstrate a 1 × 4 tunable multiplexer/demultiplexer using the Si(3)N(4)-on-SOI dual-level grating couplers and thermally-tuned Si microring resonators.
Cytidine deaminases are single stranded DNA mutators diversifying antibodies and restricting viral infection. Improper access to the genome leads to translocations and mutations in B cells and contributes to the mutation landscape in cancer, such as kataegis. It remains unclear how deaminases access double stranded genomes and whether off-target mutations favor certain loci, although transcription and opportunistic access during DNA repair are thought to play a role. In yeast, AID and the catalytic domain of APOBEC3G preferentially mutate transcriptionally active genes within narrow regions, 110 base pairs in width, fixed at RNA polymerase initiation sites. Unlike APOBEC3G, AID shows enhanced mutational preference for small RNA genes (tRNAs, snoRNAs and snRNAs) suggesting a putative role for RNA in its recruitment. We uncover the high affinity of the deaminases for the single stranded DNA exposed by initiating RNA polymerases (a DNA configuration reproduced at stalled polymerases) without a requirement for specific cofactors.
There has been an increase in the prevalence of morbid obesity and the demand for total knee arthroplasty (TKA). Physicians must help patients with bilateral knee arthritis to make informed decisions regarding whether to undergo staged, sequential, or simultaneous TKA. The purpose of this study was to evaluate the perioperative complications of 2-team simultaneous bilateral TKA in the morbidly obese. The authors performed a retrospective review of the records at a single tertiary hospital from 1997 to 2007 and identified 35 morbidly obese (body mass index [BMI] greater than 40 kg/m(2)) patients who had undergone unilateral TKA, as well as 42 morbidly obese and 79 nonobese (BMI less than 30 kg/m(2)) patients who underwent simultaneous bilateral TKA. Clinical, operative, and postoperative variables and complication rates were recorded. Clinical variables were similar between the morbidly obese TKA patients. The bilateral group had significantly increased operative times (132.4 vs 115.5 minutes; P<.01), intravenous fluids (2556.1 vs 2114.7 mL; P=.03), percentage transfused (64.2% vs 11.4%; P<.01), days in the hospital (3.6 vs 3.2 days; P=.03), and discharge rates to rehabilitation facility (72.7% vs 48.6%; P=.01). Major and minor complications were few and comparable, with the need for manipulation under anesthesia in unilateral TKA (11.4%; P=.04) as the only significant difference between groups, including when comparing bilateral nonobese TKAs with bilateral morbidly obese TKAs. The authors feel that morbidly obese patients may undergo 2-team simultaneous bilateral TKA after careful discussion regarding some of the differences in short-term outcomes.
We demonstrate various silicon-on-insulator polarization management structures based on a polarization rotator-splitter that uses a bi-level taper TM0-TE1 mode converter. The designs are fully compatible with standard active silicon photonics platforms with no new levels required and were implemented in the IME baseline and IME-OpSIS silicon photonics processes. We demonstrate a polarization rotator-splitter with polarization crosstalk < -13 dB over a bandwidth of 50 nm. Then, we improve the crosstalk to < -22 dB over a bandwidth of 80 nm by integrating the polarization rotator-splitter with directional coupler polarization filters. Finally, we demonstrate a polarization controller by integrating the polarization rotator-splitters with directional couplers, thermal tuners, and PIN diode phase shifters.
Public reporting of mortality, Patient Safety Indicators (PSI) and hospital-acquired conditions (HACs) is the reality of quality measurement. A review of our department's data identified opportunities for improvement. We began a surgeon-led 100% review of mortality, PSIs, and HACs to improve patient care and surgeon awareness of these metrics.
Since the original description by Letournel in 1961, the ilioinguinal approach has remained the predominant approach for anterior acetabular fixation. However, modifications of the original abdominal approach described by Stoppa have made another option available for reduction and fixation of pelvic and acetabular fractures.
We examined the feasibility of using a remotely maneuverable robot to make home hazard assessments for fall prevention. We employed use-case simulations to compare robot assessments with in-person assessments. We screened the homes of nine elderly patients (aged 65 years or more) for fall risks using the HEROS screening assessment. We also assessed the participants perspectives of the remotely-operated robot in a survey. The nine patients had a median Short Blessed Test score of 8 (interquartile range, IQR 2-20) and a median Life-Space Assessment score of 46 (IQR 27-75). Compared to the in-person assessment (mean?=?4.2 hazards identified per participant), significantly more home hazards were perceived in the robot video assessment (mean?=?7.0). Only two checklist items (adequate bedroom lighting and a clear path from bed to bathroom) had more than 60% agreement between in-person and robot video assessment. Participants were enthusiastic about the robot and did not think it violated their privacy. The study found little agreement between the in-person and robot video hazard assessments. However, it identified several research questions about how to best use remotely-operated robots.
Migrations between different habitats are key events in the lives of many organisms. Such movements involve annually recurring travel over long distances usually triggered by seasonal changes in the environment. Often, the migration is associated with travel to or from reproduction areas to regions of growth. Young anadromous Atlantic salmon (Salmo salar) emigrate from freshwater nursery areas during spring and early summer to feed and grow in the North Atlantic Ocean. The transition from the freshwater (parr) stage to the migratory stage where they descend streams and enter salt water (smolt) is characterized by morphological, physiological and behavioural changes where the timing of this parr-smolt transition is cued by photoperiod and water temperature. Environmental conditions in the freshwater habitat control the downstream migration and contribute to within- and among-river variation in migratory timing. Moreover, the timing of the freshwater emigration has likely evolved to meet environmental conditions in the ocean as these affect growth and survival of the post-smolts. Using generalized additive mixed-effects modelling, we analysed spatio-temporal variations in the dates of downstream smolt migration in 67 rivers throughout the North Atlantic during the last five decades and found that migrations were earlier in populations in the east than the west. After accounting for this spatial effect, the initiation of the downstream migration among rivers was positively associated with freshwater temperatures, up to about 10 °C and levelling off at higher values, and with sea-surface temperatures. Earlier migration occurred when river discharge levels were low but increasing. On average, the initiation of the smolt seaward migration has occurred 2.5 days earlier per decade throughout the basin of the North Atlantic. This shift in phenology matches changes in air, river, and ocean temperatures, suggesting that Atlantic salmon emigration is responding to the current global climate changes.
This study presents a techno-economic assessment of algae-derived biodiesel under economic and technical uncertainties associated with the development of algal biorefineries. A global sensitivity analysis was performed using a High Dimensional Model Representation (HDMR) method. It was found that, considering reasonable ranges over which each parameter can vary, the sensitivity of the biodiesel production cost to the key input parameters decreases in the following order: algae oil content>algae annual productivity per unit area>plant production capacity>carbon price increase rate. It was also found that the Return on Investment (ROI) is highly sensitive to the algae oil content, and to a lesser extent to the algae annual productivity, crude oil price and price increase rate, plant production capacity, and carbon price increase rate. For a large scale plant (100,000tonnes of biodiesel per year) the production cost of biodiesel is likely to be £0.8-1.6 per kg.
Plate fixation of displaced clavicle fractures has proven to be reliable and reproducible, leading to high union rates and a low rate of associated complications. However, the decision of whether to place the plate superiorly or anteroinferiorly on the clavicle has remained controversial. The authors performed a retrospective review on a consecutive series of patients who underwent plate fixation for a displaced midshaft clavicle fracture at a Level I urban trauma center. A review of surgical records identified 138 patients with a displaced midshaft clavicle fracture requiring operative stabilization. A total of 105 patients who met the inclusion criteria were included in the analysis. Both superior and anteroinferior techniques resulted in a similar time to radiographic union (12.6±4.8 vs 11.3±5.2 weeks, respectively) and identical union rates (95%). At final follow-up, patient-reported implant prominence was nearly double in patients with a retained superior plate (54% vs 29%, respectively; P=.04). No significant difference existed in mean visual analog scale score at a mean of 2.77 years postoperatively, although a significant difference existed in the Oxford Shoulder Score questionnaire, with a mean score of 41.4 in the superior group and 44.4 in the anteroinferior group (P=.008). Implant removal occurred more frequently after superior plating but was not significant. Both superior and anteroinferior clavicle plating are safe treatment methods for displaced clavicle fractures. Superior plating leads to an increased rate of patient-reported implant prominence and may prompt more requests for implant removal.
Physicians increasingly investigate, work, and teach to improve the quality of care and safety of care delivery. The Society of General Internal Medicine Academic Hospitalist Task Force sought to develop a practical tool, the quality portfolio, to systematically document quality and safety achievements. The quality portfolio was vetted with internal and external stakeholders including national leaders in academic medicine. The portfolio was refined for implementation to include an outlined framework, detailed instructions for use and an example to guide users. The portfolio has eight categories including: (1) a faculty narrative, (2) leadership and administrative activities, (3) project activities, (4) education and curricula, (5) research and scholarship, (6) honors, awards, and recognition, (7) training and certification, and (8) an appendix. The authors offer this comprehensive, yet practical tool as a method to document quality and safety activities. It is relevant for physicians across disciplines and institutions and may be useful as a standalone document or as an adjunct to traditional promotion documents. As the Next Accreditation System is implemented, academic medical centers will require faculty who can teach and implement the systems-based practice requirements. The quality portfolio is a method to document quality improvement and safety activities.
Dislocation of the scapula is a rare disorder. The nomenclature in the literature can be confusing as a result of nonspecific terms such as locked scapula and dislocated scapula when referring to both intra- and extra-thoracic dislocations. After a thorough review of the literature we further define and classify scapular dislocations to better understand prognosis and patient education. We report a case of a low-energy intrathoracic dislocation of the scapula due to anomalous anatomy. Similar to another reported case in the literature, we have been able to document recurrence of intrathoracic scapular dislocation only in association with persistent chest wall defects following rib resection.
Ikaros family DNA-binding proteins are critical regulators of B-cell development. Because the current knowledge of Ikaros targets in B-cell progenitors is limited, we have identified genes that are bound and regulated by Ikaros in pre-B cells. To elucidate the role of Ikaros in B-cell lineage specification and differentiation, we analyzed the differential expression of Ikaros targets during the progression of multipotent to lymphoid-restricted progenitors, B- and T-cell lineage specification, and progression along the B-cell lineage. Ikaros targets accounted for one-half of all genes up-regulated during B-cell lineage specification in vivo, explaining the essential role of Ikaros in this process. Expression of the Ikaros paralogs Ikzf1 and Ikzf3 increases incrementally during B-cell progenitor differentiation, and, remarkably, inducible Ikaros expression in cycling pre-B cells was sufficient to drive transcriptional changes resembling the differentiation of cycling to resting pre-Bcells in vivo. The data suggest that Ikaros transcription factor dosage drives the progression of progenitors along a predetermined lineage by regulating multiple targets in key pathways, including pre-B–cell receptor signaling, cell cycle progression, and lymphocyte receptor rearrangement.Our approachmay be of general use to map the contribution of transcription factors to cell lineage commitment and differentiation.
Operative management of thoracic injuries is an increasingly accepted technique, with multiple reports of improved patient outcomes as compared with nonoperative treatment. Despite the evolving support of rib fracture fixation, descriptions of surgical approaches and tactics remain limited. We present this information to allow surgeons to begin or improve treatment of these injuries. In addition, we present the initial treatment results of a series of 21 patients treated with the approaches described within.
Breast cancer genomes have revealed a novel form of mutation showers (kataegis) in which multiple same-strand substitutions at C:G pairs spaced one to several hundred nucleotides apart are clustered over kilobase-sized regions, often associated with sites of DNA rearrangement. We show kataegis can result from AID/APOBEC-catalysed cytidine deamination in the vicinity of DNA breaks, likely through action on single-stranded DNA exposed during resection. Cancer-like kataegis can be recapitulated by expression of AID/APOBEC family deaminases in yeast where it largely depends on uracil excision, which generates an abasic site for strand breakage. Localized kataegis can also be nucleated by an I-SceI-induced break. Genome-wide patterns of APOBEC3-catalyzed deamination in yeast reveal APOBEC3B and 3A as the deaminases whose mutational signatures are most similar to those of breast cancer kataegic mutations. Together with expression and functional assays, the results implicate APOBEC3B/A in breast cancer hypermutation and give insight into the mechanism of kataegis. DOI:http://dx.doi.org/10.7554/eLife.00534.001.
The aim of this paper was to show that easily interpretable maps of local and national prescribing data, available from open sources, can be used to demonstrate meaningful variations in prescribing performance.
Total knee arthroplasty (TKA) has a well-established track record for relieving pain associated with arthritis of the knee joint. The total rate of bilateral TKA has doubled over the past 2 decades, and the rate in women has tripled over that same time period. In patients with bilateral knee arthritis, a decision must be made whether to operate at 2 different settings (staged), a single setting with 1 surgeon (sequential simultaneous), or a single setting with 2 surgeons (2-team simultaneous). The purpose of this study was to examine the perioperative morbidity and mortality of 2-team simultaneous bilateral TKA. Two hundred twenty-seven consecutive 2-team simultaneous bilateral TKA and 216 consecutive unilateral TKA patients were reviewed. Major (deep infection, death, cerebrovascular accident, myocardial infarction, pulmonary embolism, revision within the 1-year follow-up) and minor (all other) complications were compared. No deaths occurred, and the major and minor complication rates were not statistically significantly different between the 2 groups, but a trend toward higher rates of both major and minor complications existed in the bilateral TKA group. Two-team simultaneous bilateral TKA offers the potential benefits of decreased overall recovery time, decreased overall cost, decreased number of anesthetic administrations, and simultaneous correction of significant deformity. It remains an appropriate option in select patients.
Gluteal compartment syndrome as a result of hematoma from a ruptured superior gluteal artery is exceedingly rare; to date, one similar case in a pelvic fracture model has been reported. We report a case of acute gluteal compartment syndrome from a ruptured superior gluteal artery resulting from a simple posterior hip dislocation in an otherwise healthy young male. Timely surgical exploration, evacuation of the hematoma, and achievement of hemostasis allowed for an excellent outcome at follow-up. We review the gluteal compartments as well as treatment protocols for this injury.
Treatment of adult femoral shaft fractures typically involves operative stabilization with intramedullary implants, external fixation, or a plate and screw construct. However, when stabilization is delayed for any reason, use of a traction pin is recommended to stabilize the fracture, prevent significant shortening, as well as to help with pain control. In this paper, we present the rare complication of a severe gas gangrene infection caused by Clostridium perfringens that led to several amputations and ultimately death. We also discuss risks of temporary skeletal traction and techniques to overcome the morbidity of such a procedure.
Fracture fixation of the medial malleolus in rotationally unstable ankle fractures typically results in healing with current fixation methods. However, when failure occurs, pullout of the screws from tension, compression, and rotational forces is predictable. We sought to biomechanically test a relatively new technique of bicortical screw fixation for medial malleoli fractures. Also, the AO group recommends tension-band fixation of small avulsion type fractures of the medial malleolus that are unacceptable for screw fixation. A well-documented complication of this technique is prominent symptomatic implants and secondary surgery for implant removal. Replacing stainless steel 18-gauge wire with FiberWire suture could theoretically decrease symptomatic implants. Therefore, a second goal was to biomechanically compare these 2 tension-band constructs. Using a tibial Sawbones model, 2 bicortical screws were compared with 2 unicortical cancellous screws on a servohydraulic test frame in offset axial, transverse, and tension loading. Second, tension-band fixation using stainless steel wire was compared with FiberWire under tensile loads. Bicortical screw fixation was statistically the stiffest construct under tension loading conditions compared to unicortical screw fixation and tension-band techniques with FiberWire or stainless steel wire. In fact, unicortical screw fixation had only 10% of the stiffness as demonstrated in the bicortical technique. In a direct comparison, tension-band fixation using stainless steel wire was statistically stiffer than the FiberWire construct.
The Orthopaedic In-Training Examination is a comprehensive test produced annually by the American Academy of Orthopaedic Surgeons, and was first administered in 1963. At the time of the examinations conception, its objectives were to: (1) measure the knowledge of orthopedic residents and provide objective comparisons; (2) help determine acceptable minimal standards for trainees; and (3) help provide an objective assessment of orthopedic education. We retrospectively reviewed all Orthopaedic In-Training Examinations from 2004 to 2008, with particular focus on the questions listed in the musculoskeletal trauma domain on each years program director report. The musculoskeletal trauma domain, including topics, recommended answers, and references, was reviewed to provide an educational resource for residents and residency programs when studying or designing educational curricula. The information in this analysis may help in development of a core musculoskeletal trauma knowledge base or facilitate determination of appropriate journal club and didactic lecture content.
This article presents a case of a 90-year-old woman who previously underwent a common femoral to anterior tibial artery bypass grafting with a Gore-Tex graft (Gore Medical, Flagstaff, Arizona). She subsequently sustained an ipsilateral intertrochanteric hip fracture after a mechanical fall and underwent internal fixation with an intramedullary nail using a fracture table. In the immediate postoperative period, she developed limb-threatening ischemia in her leg due to graft thrombosis. The patient underwent a successful thrombectomy and embolectomy. However, she subsequently developed nonhealing ulcers to this extremity over the course of weeks, requiring surgical debridement. Gangrene ensued and she underwent a below-the-knee amputation.Complications from the use of fracture tables have been described for perineal soft tissue injury, leg malrotation or malalignment, neurologic injury, and iatrogenic compartment syndrome of the healthy leg. Arterial complications after intramedullary fixation of femur fractures are rare and may be caused by direct arterial trauma during placement of the locking screws through the intramedullary nail. This article is the first, to our knowledge, to describe an occlusion of a lower extremity bypass graft after intramedullary fixation on a fracture table. Surgeons should be aware of potential limb threatening ischemia in patients with peripheral vascular disease, especially in those with prior lower extremity bypass grafts. Proper preoperative counseling should be given to these patients when using fracture tables during hip fracture surgery.
The alcohol-attributable fraction for injury mortality is defined as the proportion of fatal injury that would disappear if consumption went to zero. Estimating this fraction has previously been based on a simplistic view of drinking and associated risk. This paper develops a new way to calculate the alcohol-attributable fraction for injury based on different dimensions of drinking, mortality data, experimental data, survey research, new risk scenarios, and by incorporating different distributions of consumption within populations. For this analysis, the Canadian population in 2005 was used as the reference population.
Nuclear proteins typically contain short stretches of basic amino acids (nuclear localization sequences; NLSs) that bind karyopherin ? family members, directing nuclear import. Here, we identify CTNNBL1 (catenin-?-like 1), an armadillo motif-containing nuclear protein that exhibits no detectable primary sequence homology to karyopherin ?, as a novel, selective NLS-binding protein. CTNNBL1 (a single-copy gene conserved from fission yeast to man) was previously found associated with Prp19-containing RNA-splicing complexes as well as with the antibody-diversifying enzyme AID. We find that CTNNBL1 association with the Prp19 complex is mediated by recognition of the NLS of the CDC5L component of the complex and show that CTNNBL1 also interacts with Prp31 (another U4/U6.U5 tri-snRNP-associated splicing factor) through its NLS. As with karyopherin ?s, CTNNBL1 binds NLSs via its armadillo (ARM) domain, but displays a separate, more selective NLS binding specificity. Furthermore, the CTNNBL1/AID interaction depends on amino acids forming the AID conformational NLS with CTNNBL1-deficient cells showing a partial defect in AID nuclear accumulation. However, in further contrast to karyopherin ?s, the CTNNBL1 N-terminal region itself binds karyopherin ?s (rather than karyopherin ?), suggesting a function divergent from canonical nuclear transport. Thus, CTNNBL1 is a novel NLS-binding protein, distinct from karyopherin ?s, with the results suggesting a possible role in the selective intranuclear targeting or interactions of some splicing-associated complexes.
Treatment of severe lower extremity trauma, diabetic complications, infections, dysvascular limbs, neoplasia, developmental pathology, or other conditions often involves amputation of the involved extremity. However, techniques of lower extremity amputation have largely remained stagnant over decades. This article reports a reproducible technique for transtibial osteomyoplastic amputation.
Fever and leukocytosis are common after joint arthroplasty, often resulting in additional studies. This study was conducted to determine the incidence of fever and leukocytosis after joint arthroplasty and the use of tests. We retrospectively reviewed records (n = 426) of patients who underwent knee or hip arthroplasty between February 2006 and April 2008 to determine the incidence of fever and leukocytosis, tests, and results. Sixty-four had fever, and 247 had postoperative leukocytosis. Sixty additional tests were performed; 6 (10%) of 60 tests were clinically relevant. After joint arthroplasty, more than half of patients developed leukocytosis, and nearly 15% developed fever. Diagnostic testing should be based on physical examination or symptomatic findings and not solely on laboratory values or vital signs, decreasing the patient discomfort and potentially lower costs.
Controlling male fertility is an important goal for plant reproduction and selective breeding. Hybrid vigour results in superior growth rates and increased yields of hybrids compared with inbred lines; however, hybrid generation is costly and time consuming. A better understanding of anther development and pollen release will provide effective mechanisms for the control of male fertility and for hybrid generation. Male sterility is associated not only with the lack of viable pollen, but also with the failure of pollen release. In such instances a failure of anther dehiscence has the advantage that viable pollen is produced, which can be used for subsequent rescue of fertility. Anther dehiscence is a multistage process involving localized cellular differentiation and degeneration, combined with changes to the structure and water status of the anther to facilitate complete opening and pollen release. After microspore release the anther endothecium undergoes expansion and deposition of ligno-cellulosic secondary thickening. The septum separating the two locules is then enzymatically lysed and undergoes a programmed cell death-like breakdown. The stomium subsequently splits as a consequence of the stresses associated with pollen swelling and anther dehydration. The physical constraints imposed by the thickening in the endothecium limit expansion, placing additional stress on the anther, so as it dehydrates it opens and the pollen is released. Jasmonic acid has been shown to be a critical signal for dehiscence, although other hormones, particularly auxin, are also involved. The key regulators and physical constraints of anther dehiscence are discussed.
Orthopedic resident training involves not only the hands-on learning of surgery but also should equally involve instructing the core knowledge of musculoskeletal medicine. Our program has developed a strategy that enhances resident educational performance; the educational curriculum entails conferences daily. Conferences include gross and surgical anatomy, orthopedic basic science, multidisciplinary trauma, radiology, pathology, journal club, and orthopedic subspecialty conferences. The primary purpose of the conference schedule is to provide the residents with a comprehensive education in orthopedic surgery. It is not geared toward taking the Orthopaedic In-Training Examination (OITE). The OITE is administered annually by the American Academy of Orthopaedic Surgeons (AAOS) and serves as an objective measure of knowledge acquisition. There has been a scientifically validated correlation between performance on the OITE and passage of the American Board for Orthopaedic Surgery Part I Examination. As a collective program, we have achieved at or above the 98th percentile nationally from 2004 to 2009. This academic success has not impacted the total surgical case volume negatively or interfered with Residency Review Committee (RRC) policies.
According to the World Health Organization, the public health impact of illicit alcohol and informally produced alcohol should be reduced. This paper summarizes and evaluates the evidence base about policy and intervention options regarding unrecorded alcohol consumption.
Slipped capital femoral epiphysis is a common injury suffered by adolescents worldwide. Treatment of most slips can be accomplished by percutaneous screw fixation, as this is an accepted and proven method associated with minimal morbidity. Complications, although limited, can be problematic for both the patient and treating physician. These include avascular necrosis, chondrolysis, infection, and fracture. We report a case of an individual who sustained a subtrochanteric femure fracture three weeks after in situ pinning of his left hip treated with a reconstruction intramedullary nail. This option allowed both the subtrochanteric fracture and SCFE to be treated concomitantly with minimized morbidity.
This article describes a case of a 26-year-old man presenting with left knee pain of 1 weeks duration, fever, and acute onset of shortness of breath the day of admission. An arthrocentesis of the knee joint was grossly positive for methicillin-resistant Staphylococcus aureus. A left lower extremity venous duplex showed thrombosis of the superficial femoral, popliteal, posterior tibial, peroneal, and gastrocnemius veins. Pulmonary computed tomography-angiography was positive for acute pulmonary emboli. Initial management consisted of anticoagulation, intravenous antibiotics, and 2 arthroscopic irrigation and debridement procedures. After a normal transesophageal echocardiogram, a diagnosis of septic knee-induced deep venous thrombosis (DVT) of the left lower leg with subsequent septic pulmonary emboli was established. The patient was discharged to a long-term care facility for a 6-week monitored course of intravenous antibiotics. His DVT and pulmonary emboli were managed successfully with oral warfarin. Two months after his initial presentation, the patient returned with acute worsening knee pain. A knee arthrocentesis was unremarkable; however, radiographic imaging revealed fulminant osteomyelitis of the distal femur. He has since undergone open arthrotomy with excisional irrigation and debridement and is on a chronic oral antibiotic regimen. Sparse pediatric literature has shown an association between musculoskeletal sepsis and thrombosis. Only 1 case of septic knee-induced DVT exists in the adult literature, and it was not associated with pulmonary emboli. Our case provides evidence that DVT must be considered by the treating physician as a possible and devastating complication of septic arthritis.
We hypothesized that patients undergoing transtibial amputation osteomyoplasty would have better functional outcomes than patients undergoing traditional transtibial amputation. We conducted a retrospective review of the medical and radiographic records to evaluate and compare 26 patients who underwent transtibial amputation osteomyoplasty and 10 patients who underwent traditional transtibial amputation, with specific attention to perioperative complications and functional outcomes. At >1 year follow-up, patients who underwent amputation osteomyoplasty had significantly improved rates of return to work and decreased rates of revision than patients who underwent traditional transtibial amputation. Sickness Impact Profile questionnaire results completed at a mean of 28 months postoperatively showed significantly better overall scores and physical and psychosocial dimension scores for amputation osteomyoplasty patients. Based on the results of this study, the outcomes of amputation osteomyoplasty appear to be safe and may be more beneficial than traditional amputation, in terms of improved functional outcomes for patients after severe lower-extremity trauma.
Activation-induced deaminase (AID) is a B lymphocyte-specific DNA deaminase that triggers Ig class-switch recombination (CSR) and somatic hypermutation. It shuttles between cytoplasm and nucleus, containing a nuclear export sequence (NES) at its carboxyterminus. Intriguingly, the precise nature of this NES is critical to AIDs function in CSR, though not in somatic hypermutation. Many alterations to the NES, while preserving its nuclear export function, destroy CSR ability. We have previously speculated that AIDs ability to potentiate CSR may critically depend on the affinity of interaction between its NES and Crm1 exportin. Here, however, by comparing multiple AID NES mutants, we find that - beyond a requirement for threshold Crm1 binding - there is little correlation between CSR and Crm1 binding affinity. The results suggest that CSR, as well as the stabilisation of AID, depend on an interaction between the AID C-terminal decapeptide and factor(s) additional to Crm1.
While foraging, social insects encounter a dynamic array of food resources of varying quality and profitability. Because food acquisition influences colony growth and fitness, natural selection can be expected to favor colonies that allocate their overall foraging effort so as to maximize their intake of high-quality nutrients. Social wasps lack recruitment communication, but previous studies of vespine wasps have shown that olfactory cues influence foraging decisions. Odors associated with food brought into the nest by successful foragers prompt naive foragers to leave the nest and search for the source of those odors. Left unanswered, however, is the question of whether naive foragers take food quality into account in making their decisions about whether or not to search. In this study, two different concentrations of sucrose solutions, scented differently, were inserted directly into each of three Vespula germanica nests. At a feeder away from the nest, arriving foragers were given a choice between two 1.5 M sucrose solutions with the same scents as those in the nest. We show that wasps chose higher-quality resources in the field using information in the form of intranidal food-associated odor cues. By this simple mechanism, the colony can bias the allocation of its foraging effort toward higher-quality resources in the environment.
Neuroarthropathy of the foot and ankle is a relatively common complication of diabetes mellitus. Likewise, neuroarthropathy of the shoulder has been well reported in relation to syringomyelia. Diabetes mellitus, however, has rarely been reported to cause neuroarthropathy of any joint in the upper extremity and has never previously been reported in the shoulder. This article presents a case of a 77-year-old woman who presented with a secondary complaint of mild right shoulder pain, which had been present since she sustained a proximal humerus fracture four months earlier. The patients past medical history was notably positive for diabetes mellitus with substantial peripheral neuropathy in the upper and lower extremities. Radiographic examination revealed significant degeneration of the humeral head, consistent with neuroarthropathy of the shoulder. Computed tomography and magnetic resonance imaging demonstrated no syrinx within the spinal cord. The patients medical history included no etiologies of neuroarthropathy of the shoulder that had been previously reported in the literature. After a thorough literature review, we believe this to be the first case of diabetic shoulder neuroarthropathy to be documented. No significant differences in clinical or radiographic presentations appear to be present between reported etiologies of this pathology, including diabetes mellitus. Consequently, we recommend that diabetes mellitus always be considered as an etiology in the differential diagnosis of neuroarthropathy of the shoulder.
Alcohol is an established risk factor for liver cirrhosis. It remains unclear, however, whether this relationship follows a continuous dose-response pattern or has a threshold. Also, the influences of sex and end-point (i.e. mortality vs. morbidity) on the association are not known. To address these questions and to provide a quantitative assessment of the association between alcohol intake and risk of liver cirrhosis, we conducted a systematic review and meta-analysis of cohort and case-control studies.
Although the rates of perioperative morbidity and mortality with simultaneous bilateral total knee arthroplasty remain a concern, multiple studies have shown the procedure to be safe in selected patient populations. Evidence also remains mixed regarding the outcomes of total knee arthroplasty in obese patients. The purpose of this paper is to compare the rates of perioperative morbidity and mortality in consecutive obese patients undergoing two-team simultaneous bilateral total knee arthroplasty and unilateral total knee arthroplasty.
This study explores whether or not foragers of the Neotropical swarm-founding wasp Polybia occidentalis use nest-based recruitment to direct colony mates to carbohydrate resources. Recruitment allows social insect colonies to rapidly exploit ephemeral resources, an ability especially advantageous to species such as P. occidentalis, which store nectar and prey in their nests. Although recruitment is often defined as being strictly signal mediated, it can also occur via cue-mediated information transfer. Previous studies indicated that P. occidentalis employs local enhancement, a type of cue-mediated recruitment in which the presence of conspecifics at a site attracts foragers. This recruitment is resource-based, and as such, is a blunt recruitment tool, which does not exclude non-colony mates. We therefore investigated whether P. occidentalis also employs a form of nest-based recruitment. A scented sucrose solution was applied directly to the nest. This mimicked a scented carbohydrate resource brought back by employed foragers, but, as foragers were not allowed to return to the nest with the resource, there was no possibility for on-nest recruitment behavior. Foragers were offered two dishes--one containing the test scent and the other an alternate scent. Foragers chose the test scent more often, signifying that its presence in the nest induces naïve foragers to search for it off-nest. P. occidentalis, therefore, employs a form of nest-based recruitment to carbohydrate resources that is mediated by a cue, the presence of a scented resource in the nest.
The negative health consequences of alcohol use and its treatment account for significant health care expenditure worldwide. Long-term modelling techniques are developed in this paper to establish a link between drinking patterns, health consequences and alcohol treatment effectiveness and cost-effectiveness. The overall change in health related quality and quantity of life which results from changes in health-related behaviour is estimated. Specifically, a probabilistic lifetime Markov model is presented where alcohol consumption in grams of alcohol per day and drinking history are used for the categorization of patients into four Markov states. Utility weights are assigned to each drinking state using EQ-5D scores. Mortality and morbidity estimates are state, gender and age specific, and are alcohol-related and non-alcohol-related. The methodology is tested in a case study. This represents a major development in the techniques traditionally used in alcohol economic models, in which short-term costs and outcomes are assessed, omitting potential longer term cost savings and improvements in health related quality of life. Assumptions and implications of the approach are discussed.
Observational studies have suggested a complex relationship between alcohol consumption and stroke, dependent on sex, type of stroke and outcome (morbidity vs. mortality). We undertook a systematic review and a meta-analysis of studies assessing the association between levels of average alcohol consumption and relative risks of ischemic and hemorrhagic strokes separately by sex and outcome. This meta-analysis is the first to explicitly separate morbidity and mortality of alcohol-attributable stroke and thus has implications for public health and prevention.
As part of a larger study to estimate the global burden of disease and injury attributable to alcohol: to evaluate the evidence for a causal impact of average volume of alcohol consumption and pattern of drinking on diseases and injuries; to quantify relationships identified as causal based on published meta-analyses; to separate the impact on mortality versus morbidity where possible; and to assess the impact of the quality of alcohol on burden of disease.
The pH of the tongue biofilm is likely to influence microbial composition and ecology with consequent effects on the metabolic activities and generation of volatile sulfur compounds (VSC) and other malodour gasses. The aim of this study was to identify the effects of pH on the development of biofilms and hydrogen sulfide production using an in vitro tongue-derived biofilm model. Community level physiological profiling (CLPP) was employed to examine the influence of pH on the collective metabolic fingerprint of each tongue-derived biofilm. A sorbarod perfusion system (n = 6 sorbarods) was inoculated from a single suspension of tongue scrape sample and mixed community tongue-derived biofilms were grown at pH 5.5, 6.0, 6.5, 7.0 7.5 and 8.0. Biofilms were perfused with medium for 120 h and gas phase samples (n = 4 per biofilm) removed and analysed with a portable sulfide gas chromatograph before being sacrificed into 10 ml sterile PBS-diluent and cells suspended by vortex mixing. Further ten-fold dilutions were made (down to 10(-7)) and dilutions plated out onto selective (fastidious anaerobic agar (FAA) + 0.0025% vancomycin) and non-selective (FAA) media for enumeration of strict and facultative anaerobes respectively. Biofilm suspensions were also mixed with Biolog inoculation fluid and distributed into 96 wells of Biolog AN plates for CLPP. Tongue biofilms developed at pH 7.5 produced significant (p < 0.05) concentrations of H(2)S (?52.2 ± SEM 5.6 µg H(2)S per ml biofilm gas phase) followed by tongue biofilm developed at pH 7.0 and 8.0 (?43.2 ± SEM 3.5 and ? 39.6 ± SEM 7.3 µg H(2)S per ml biofilm gas phase respectively). Tongue biofilm developed at pH 6.0 and 6.5 produced approximately 21.5 ± SEM 2.3 and 37.1 ± SEM 1.7 µg H(2)S per ml biofilm gas phase respectively and tongue biofilm developed at pH 5.5 produced approximately 0.19 ± SEM 0.09 µg H(2)S per ml biofilm gas phase. Highest numbers of strict and facultative anaerobes were recovered from biofilms at pH 6.5 (1.10 × 10(12) and 2.07 × 10(12) cfu ml(-1) respectively), with a reduced number recovered from pH values above and below this range. CLPP and similarity index revealed biofilms at pH 6.5 and 7.0 most similar (S(j) = 78%) and most diverse in terms of metabolic activity. The biofilm at pH 5.5 was the least related to all others and least diverse. The sorbarod perfusion system, in conjunction with H(2)S analysis and CLPP, enables some of the physiological and ecological effects of pH at a local level within the biofilm on H(2)S production to be identified.
Naive CD4 T cells differentiate into functionally distinct T helper (Th) cells subsets or into regulatory T (Treg) cells in response to the cytokine milieu in which they encounter antigen. A recurring theme in post-thymic CD4 T cell differentiation is the cross-regulation of lineage choice by cytokines and transcription factors that are expressed in alternative lineages. For example, TGFbeta induces the de novo expression of the Treg cell signature transcription factor Foxp3, but iTreg differentiation is blocked by high concentrations of the Th2 cytokine IL4. However, whether IL4 can antagonise Foxp3 induction in more physiological settings remains to be addressed. Here we use a co-culture system to demonstrate that IL4 provided by Th2 cells in vitro is sufficient to block Foxp3 induction in naive CD4 T cells. In addition, we find that Foxp3 induction is efficiently blocked not only by the Th2 transcription factor Gata3, but also by PU.1, which is transiently induced during Th2 differentiation. These data suggest that iTreg differentiation may be affected by the polarity of immune responses.
Total hip and total knee arthroplasty are high-volume surgical procedures that have a substantial economic impact for the healthcare system. This study analyzes the financial effect of a capitation matrix system on total knee and total hip implant costs over a 1-year period at a community hospital system. The matrix implant levels were based on implant characteristics, correlating increased technological sophistication of the various implants with increased but capitated payment to vendors. In the first year after the implementation of the matrix system, implant costs for the hospital decreased by 26.1% per implant for 369 total hip procedures and also by 26.1% per implant for 934 total knee procedures.
Simultaneous bilateral patellar tendon ruptures are extremely rare, and even more rare in patients without systemic disease. We describe bilateral simultaneous patellar tendon disruptions in the absence of systemic disease or steroid usage, with one tendon disruption at the inferior pole and the other an intrasubstance tear. The different locations of the ruptures are also exceedingly rare, as only two cases of non-identical ruptures have ever been reported. We also review all bilateral patellar tendon rupture case reports from English and German literature.
This report represents an interesting case of a rare distal focal femoral deficiency with a complication of hip dislocation. The deformity at the distal femur was erroneously given an initial diagnosis of proximal focal femoral deficiency, and we believe that other similar patients have been given this incorrect diagnosis. Additional reports of such patients will allow further identification of associated pathology. This study describes the features of distal focal femoral deficiency, potential orthopaedic concerns, and proposes a classification scheme for this pathology.
Intraoperative disruption of the medial collateral ligament during total knee arthroplasty is an uncommon complication that can be avoided by retractor placement as well as by careful cutting of the femur and tibia. This study evaluated the excursion of a small and large oscillating saw blade and compared the data against the widths of both the medial and lateral femoral condyle cuts. We discovered that the large saw blade had a statistically significantly larger excursion than the medial and lateral condyle width in women, as well as the lateral condyle width in men. The small saw blade excursion did not exceed any condyle width. We conclude that the smaller saw blade should be considered when making these cuts because the excursion of the large saw blade may exceed the width of cut needed and endanger important structures such as collateral ligaments.
Deformed wing virus (DWV) in western honey bees (Apis mellifera) often remains asymptomatic in workers and drones, and symptoms have never been described from queens. However, intense infections linked to parasitism by the mite Varroa destructor can cause worker wing deformity and death within 67 h of emergence. Ten workers (eight with deformed wings and two with normal wings) and three drones (two with deformed wings and one with normal wings) from two colonies infected with V. destructor from Nova Scotia, Canada, and two newly-emerged queens (one with deformed wings and one with normal wings) from two colonies infected with V. destructor from Prince Edward Island, Canada, were genetically analyzed for DWV. We detected DWV in all workers and drones, regardless of wing morphology, but only in the deformed-winged queen. This is the first report of DWV from Atlantic Canada and the first detection of a symptomatic queen with DWV from anywhere.
B cell development requires the coordinated rearrangement of Ig heavy (IgH) and light chain loci (IgL). Most mature B cells express a single B cell receptor of unique specificity, and a central question in immunology concerns the mechanisms that prevent the productive rearrangement of >1 IgH and IgL allele per cell. Probabilistic models of allelic exclusion maintain that simultaneous rearrangement of both alleles is rare, because the likelihood of undergoing rearrangement is low for a given Ig allele. Strong support for this idea came from studies in which a GFP marker was inserted into the Igk locus. In this system, the probability of high-level germ-line transcription and subsequent locus rearrangement appeared to be low in pre-B cells. Readdressing the validity of GFP expression as a reporter for the level of germ-line transcription, we found a striking discordance between GFP transcript and protein levels at the pre-B cell stage, which is explained at least in part by the developmentally regulated usage of 2 alternative Igk-J germ-line promoters. These results question the validity of the kappa-GFP system as evidence for probabilistic models of allelic exclusion.
Pulmonary complications of rib fractures typically occur in the immediate postinjury period, as a result of the forces causing the injury or subsequent rib fracture displacement. Pneumothorax, hemothorax, pulmonary contusions, or parenchymal lacerations are frequently seen with significant chest wall trauma. Hemopneumothorax is typically treated with tube thoracostomy, and full resolution of the pleural injury is expected; continued pleural fluid accumulation despite these measures is unanticipated, rare, and quite problematic. We report a case of hemorrhagic pleural effusion after rib fractures that were recurrent despite several tube thoracostomies and computed tomography-guided aspirations. The patient subsequently underwent operative fixation of her rib fractures, with successful resolution of her symptomatic pleural effusion.
Nonmedical prescription opioid use (NMPOU) has become a substantial public health concern in North America. Existing epidemiological data suggest an association between NMPOU and mental health or pain symptoms in different populations, although these correlations are not systematically assessed. To address this gap, a systematic search, review, and meta-analysis were completed separately for both mental health problem symptoms and pain in general population samples reporting NMPOU. Overall, 9 unique epidemiological studies were identified and included in the review. The pooled prevalence of any mental health symptoms in general population samples reporting NMPOU was 32% (95% confidence interval [CI]: 24-40). Specifically, the pooled prevalence of depression was 17% (95% CI: 14-19) and the prevalence of anxiety in general population samples of NMPOU was 16% (95% CI: 1-30) The pooled prevalence of pain in the population of interest was found to be 48% (95% CI: 37-59). This systematic review found evidence for disproportionately high prevalence levels of mental health problems and pain among general population samples reporting NMPOU. While the data reviewed cannot interpret dynamics of potential causality, these findings have implications for interventions for NMPOU, as well as medical practice involving prescription opioids.
The biosynthesis of gibberellic acid (GA(3)) by the fungus Fusarium fujikuroi is catalyzed by seven enzymes encoded in a gene cluster. While four of these enzymes are characterized as cytochrome P450 monooxygenases, the nature of a fifth oxidase, GA(4) desaturase (DES), is unknown. DES converts GA(4) to GA(7) by the formation of a carbon-1,2 double bond in the penultimate step of the pathway. Here, we show by expression of the des complementary DNA in Escherichia coli that DES has the characteristics of a 2-oxoglutarate-dependent dioxygenase. Although it has low amino acid sequence homology with known 2-oxoglutarate-dependent dioxygenases, putative iron- and 2-oxoglutarate-binding residues, typical of such enzymes, are apparent in its primary sequence. A survey of sequence databases revealed that homologs of DES are widespread in the ascomycetes, although in most cases the homologs must participate in non-gibberellin (GA) pathways. Expression of des from the cauliflower mosaic virus 35S promoter in the plant species Solanum nigrum, Solanum dulcamara, and Nicotiana sylvestris resulted in substantial growth stimulation, with a 3-fold increase in height in S. dulcamara compared with controls. In S. nigrum, the height increase was accompanied by a 20-fold higher concentration of GA(3) in the growing shoots than in controls, although GA(1) content was reduced. Expression of des was also shown to partially restore growth in plants dwarfed by ectopic expression of a GA 2-oxidase (GA-deactivating) gene, consistent with GA(3) being protected from 2-oxidation. Thus, des has the potential to enable substantial growth increases, with practical implications, for example, in biomass production.
Limb deformity can occur in the pediatric and adolescent populations from multiple etiologies: congenital, traumatic, posttraumatic sequelae, oncologic, and infection. Correcting these deformities is important for many reasons. Ilizarov popularized external fixation to accomplish this task. Taylor expanded on this by designing an external fixator in 1994 with 6 telescoping struts that can be sequentially manipulated to achieve multiaxial correction of deformity without the need for hinges or operative frame alterations. This frame can be used to correct deformities in children and has shown good anatomic correction with minimal morbidity. The nature of the construct and length of treatment affects psychosocial factors that the surgeon and family must be aware of prior to treatment. An understanding of applications of the Taylor Spatial Frame gives orthopedic surgeons an extra tool to correct simple and complex deformities in pediatric and adolescent patients.
The perioperative management of patients with a coronary artery stent is a major patient safety issue currently confronting clinicians. Surgery on a patient on antiplatelet therapy creates the following dilemma: is it better to withdraw the drugs and reduce the hemorrhagic risk or to maintain them and reduce the risk of a myocardial ischemic event?
Alcohol consumption causes motor vehicle accident (MVA) injury in a dose-response fashion. However, the relationship between how this risk is different with respect to fatal and nonfatal outcomes is not clear. A meta-analysis has already been completed for alcohol consumption and nonfatal MVA injury, but none exists for fatal injury. Thus, an analysis of the acute dose-response relationship between alcohol and motor vehicle injury death is warranted to generate single occasion- and dose-specific relative risks for the first time.
Cannabis use is prevalent among young people, and frequent users are at an elevated risk for health problems. Availability and effectiveness of conventional treatment are limited, and brief interventions (BIs) may present viable alternatives. One hundred thirty-four young high-frequency cannabis users from among university students were randomized to either an oral (C-O; n = 25) or a written experimental cannabis BI (C-W; n = 47) intervention group, or to either an oral (H-O; n = 25) or written health BI (H-W; n = 37) control group. Three-month follow-up assessments based on repeated measures analysis of variance techniques found a decrease in the mean number of cannabis use days in the total sample (p = 0.024), reduced deep inhalation/breathholding use in the C-O group (p = 0.003), reduced driving after cannabis use in the C-W group (p = 0.02), and a significant reduction in deep inhalation/breathholding in the C-O group (p = 0.011) compared with controls. Feasibility and short-term impact of the BIs were demonstrated, yet more research is needed.
The Gritti-Stokes amputation procedure is a modification of the traditional transfemoral amputation, with resection of the bone at a supracondylar femoral level and fixation of the patella to the distal part of the femur as an end-cap. Although well-established in patients with vascular compromise, no evidence exists on its use in the trauma setting.
Multiple surgeries are often required to manage segmental bone loss because of the complex mechanics and biology involved in reconstruction. These procedures can lead to prolonged recovery times, poor patient outcomes, and even delayed amputation. A two-stage technique uses induced biologic membranes with delayed placement of bone graft to manage this clinical challenge. In the first stage, a polymethyl methacrylate spacer is placed in the defect to produce a bioactive membrane, which appears to mature biochemically and physically 4 to 8 weeks after spacer placement. In the second, cancellous autograft is placed within this membrane and, via elution of several growth factors, the membrane appears to prevent graft resorption and promote revascularization and consolidation of new bone. Excellent clinical results have been reported, with successful reconstruction of segmental bone defects >20 cm.
Alcohol is a substantial risk factor for mortality according to the recent 2010 World Health Assembly strategy to reduce the harmful use of alcohol which outlined the need to characterize and monitor this burden. Accordingly, using new methodology we estimated 1) the number of deaths caused and prevented by alcohol consumption, and 2) the potential years of life lost (PYLLs) attributable to alcohol consumption in Canada in 2005.
SUMMARYOperative treatment of displaced patella fractures with tension band fixation remains the gold standard, but is associated with a significant rate of complications and symptomatic implants. Despite the evolution of tension band fixation to include cannulated screws, surprisingly little other development has been made to improve overall patient outcomes. In this paper, we present the techniques and outcomes of patella plating for displaced patella fractures and patella nonunions.
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