Local genetic adaptation to habitat in wild chimpanzees.

How populations adapt to their environment is a fundamental question in biology. Yet we know surprisingly little about this process, especially for endangered species such as non-human great apes. Chimpanzees, our closest living relatives, are particularly interesting because they inhabit diverse habitats, from rainforest to woodland-savannah. Whether genetic adaptation facilitates such habitat diversity remains unknown, despite having wide implications for evolutionary biology and conservation. Using 828 newly generated exomes from wild chimpanzees, we find evidence of fine-scale genetic adaptation to habitat. Notably, adaptation to malaria in forest chimpanzees is mediated by the same genes underlying adaptation to malaria in humans. This work demonstrates the power of non-invasive samples to reveal genetic adaptations in endangered populations and highlights the importance of adaptive genetic diversity for chimpanzees. One-Sentence Summary: Chimpanzees show evidence of local genetic adaptation to habitat, particularly to pathogens, such as malaria, in forests.

Understanding quality of life and patient expectations among adolescents with neonatal brachial plexus palsy: a qualitative and quantitative pilot study.

PURPOSE: To explore the quality of life (QOL) and patient expectations among adolescents with neonatal brachial plexus palsy (NBPP)and their parents using qualitative and quantitative approaches. METHODS: A total of 18 adolescents (10-17 y) with residual NBPP impairment and their parents under went separate 1-hour tape-recorded semistructured interviews. We also collected quantitative physical examination measures and patient-rated outcome scores, specifically the Pediatric Outcomes Data Collection Instrument and the Child Health Questionnaire, to quantify the severity of each adolescent's functional deficit and increase our understanding of QOL and patient expectations. RESULTS: Through qualitative analysis, we identified several patient- and system-dependent factors contributing to QOL, such as social impact and peer acceptance, emotional adjustment,aesthetic concerns and body image, functional limitations, physical and occupational therapy, finances, pain, and family dynamics. Despite residual impairment, most adolescents and their parents reported a good overall QOL according to quantitative outcome measures. Our study results showed that functional and aesthetic factors were responsible for most observed differences in QOL among NBPP adolescents. We also found that the Pediatric Outcomes Data Collection Instrument might be more sensitive than the Child Health Questionnaire in assessing patient expectations and QOL among this patient population. CONCLUSIONS: Understanding patient expectations and QOL in NBPP adolescents is essential for medical decision making and advancing care. Physical examination measurements alone may not be sufficient for measuring outcome, and knowledge regarding environmental factors and family dynamics is important for clinicians to consider when counseling families of children with NBPP and improving overall outcome. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

A national survey of program director opinions of core competencies and structure of hand surgery fellowship training.

PURPOSE: We assessed hand surgery program directors' opinions of essential components of hand surgery training and potential changes in the structure of hand surgery programs. METHODS: We recruited all 74 program directors of Accreditation Council of Graduate Medical Education-accredited hand surgery fellowship programs to participate. We designed a web-based survey to assess program directors' support for changes in the structure of training programs and to assess opinions of components that are essential for graduates to be proficient. Respondents were asked to rate 9 general areas of practice, 97 knowledge topics, and 172 procedures. Each component was considered essential if 50% or more of respondents thought that graduates must be fully knowledgeable of the topic and be able to perform the procedure at the end of training. RESULTS: The response rate was 84% (n = 62). A minority of program directors (n = 15; 24%) supported creation of additional pathways for hand surgery training, and nearly three-quarters (n = 46; 74%) preferred a fellowship model to an integrated residency model. Most program directors (n = 40; 65%) thought that a 1-year fellowship was sufficient to train a competent hand surgeon. Wrist, distal radius/ulna, forearm, and peripheral nerve conditions were rated as essential areas of practice. Of the detailed components, 76 of 97 knowledge topics and 98 of 172 procedures were rated as essential. Only 48% respondents (n = 30) rated microsurgery as it relates to free tissue transfer as essential. However, small and large vessel laceration repairs were rated as essential by 92% (n = 57) and 77% (n = 48) of respondents, respectively. CONCLUSIONS: This study found resistance to prolonging the length of fellowship training and introduction of an integrated residency pathway. To train all hand surgeons in essential components of hand surgery, programs must individually evaluate exposure provided and find innovative ways to augment training when necessary. CLINICAL RELEVANCE: Studies of curriculum content in hand surgery affect the future scope of hand surgery practice and highlight areas in need of reform and enhancement.

History and evolution of the Sauvé-Kapandji procedure.

Arthrodesis of the distal radioulnar joint combined with the creation of a pseudarthrosis of the distal ulna is frequently referred to as the Sauvé-Kapandji procedure. This eponym is based on the 1936 report by Sauvé and Kapandji, which is believed to be the first report of this innovative technique. There has been some controversy regarding the origin of this procedure, with similar techniques described by Berry in 1930 and Steindler in 1932. This article examines the evolution of the Sauvé-Kapandji procedure and sheds light on the lives of James Allan Berry, Arthur Steindler, Louis de Gonzague Sauvé, and Mehmed Kapandji.

Developing the art of scientific presentation.

PURPOSE: Few guidelines exist regarding the most effective approach to scientific oral presentations. Our purpose is to (1) develop a standardized instrument to evaluate scientific presentations based on a comprehensive review of the available literature regarding the components and organization of scientific presentations and (2) describe the optimal characteristics of scientific presentations. METHODS: At the Sixty-sixth (2011) Annual Meeting of the American Society for Surgery of the Hand, 69 presentations were evaluated by at least 2 independent observers. A rating instrument was developed a priori to examine presentation content (background, methods, results, and conclusions), presentation style (speech, structure, delivery, slide aesthetics), and overall quality. We examined correlations between reviewers' ratings of each component as well as overall perceived quality of the presentation using regression analysis. Intraclass correlation coefficients were calculated to measure the degree of variation because of reviewer disagreement and identify the aspects of presentations that contribute to overall quality. RESULTS: Reviewer agreement was high for presentation content, and less than 1% of variation was caused by reviewer disagreement for background, methods, and conclusions. With respect to presentation style, reviewers agreed most frequently regarding speech and slide appearance, and only 9% and 13%, respectively, of the variation was caused by reviewer disagreement. Disagreement was higher for delivery and presentation structure, and 21% of the variation was attributable to reviewer disagreement. Speaker delivery and slide appearance were the most important predictors of presentation quality, followed by the quality of the presentation of conclusions and background information. Presentation of methods and results were not associated with overall presentation quality. CONCLUSIONS: Distinct aspects of presentation content and style correlate with quality, which can be reliably and objectively measured. By focusing on selected concepts with visually simple slides, speakers can enhance their delivery and may potentially improve the audience's comprehension of the study findings.

Population dynamics and genetic connectivity in recent chimpanzee history.

Knowledge on the population history of endangered species is critical for conservation, but whole-genome data on chimpanzees (Pan troglodytes) is geographically sparse. Here, we produced the first non-invasive geolocalized catalog of genomic diversity by capturing chromosome 21 from 828 non-invasive samples collected at 48 sampling sites across Africa. The four recognized subspecies show clear genetic differentiation correlating with known barriers, while previously undescribed genetic exchange suggests that these have been permeable on a local scale. We obtained a detailed reconstruction of population stratification and fine-scale patterns of isolation, migration, and connectivity, including a comprehensive picture of admixture with bonobos (Pan paniscus). Unlike humans, chimpanzees did not experience extended episodes of long-distance migrations, which might have limited cultural transmission. Finally, based on local rare variation, we implement a fine-grained geolocalization approach demonstrating improved precision in determining the origin of confiscated chimpanzees.

Structure of Chimpanzee Gut Microbiomes across Tropical Africa.

Understanding variation in host-associated microbial communities is important given the relevance of microbiomes to host physiology and health. Using 560 fecal samples collected from wild chimpanzees (Pan troglodytes) across their range, we assessed how geography, genetics, climate, vegetation, and diet relate to gut microbial community structure (prokaryotes, eukaryotic parasites) at multiple spatial scales. We observed a high degree of regional specificity in the microbiome composition, which was associated with host genetics, available plant foods, and potentially with cultural differences in tool use, which affect diet. Genetic differences drove community composition at large scales, while vegetation and potentially tool use drove within-region differences, likely due to their influence on diet. Unlike industrialized human populations in the United States, where regional differences in the gut microbiome are undetectable, chimpanzee gut microbiomes are far more variable across space, suggesting that technological developments have decoupled humans from their local environments, obscuring regional differences that could have been important during human evolution. IMPORTANCE Gut microbial communities are drivers of primate physiology and health, but the factors that influence the gut microbiome in wild primate populations remain largely undetermined. We report data from a continent-wide survey of wild chimpanzee gut microbiota and highlight the effects of genetics, vegetation, and potentially even tool use at different spatial scales on the chimpanzee gut microbiome, including bacteria, archaea, and eukaryotic parasites. Microbial community dissimilarity was strongly correlated with chimpanzee population genetic dissimilarity, and vegetation composition and consumption of algae, honey, nuts, and termites were potentially associated with additional divergence in microbial communities between sampling sites. Our results suggest that host genetics, geography, and climate play a far stronger role in structuring the gut microbiome in chimpanzees than in humans.

An Automated, Single Cell Quantitative Imaging Microscopy Approach to Assess Micronucleus Formation, Genotoxicity and Chromosome Instability.

Micronuclei are small, extranuclear bodies that are distinct from the primary cell nucleus. Micronucleus formation is an aberrant event that suggests a history of genotoxic stress or chromosome mis-segregation events. Accordingly, assays evaluating micronucleus formation serve as useful tools within the fields of toxicology and oncology. Here, we describe a novel micronucleus formation assay that utilizes a high-throughput imaging platform and automated image analysis software for accurate detection and rapid quantification of micronuclei at the single cell level. We show that our image analysis parameters are capable of identifying dose-dependent increases in micronucleus formation within three distinct cell lines following treatment with two established genotoxic agents, etoposide or bleomycin. We further show that this assay detects micronuclei induced through silencing of the established chromosome instability gene, SMC1A. Thus, the micronucleus formation assay described here is a versatile and efficient alternative to more laborious cytological approaches, and greatly increases throughput, which will be particularly beneficial for large-scale chemical or genetic screens.

Environmental variability supports chimpanzee behavioural diversity.

Large brains and behavioural innovation are positively correlated, species-specific traits, associated with the behavioural flexibility animals need for adapting to seasonal and unpredictable habitats. Similar ecological challenges would have been important drivers throughout human evolution. However, studies examining the influence of environmental variability on within-species behavioural diversity are lacking despite the critical assumption that population diversification precedes genetic divergence and speciation. Here, using a dataset of 144 wild chimpanzee (Pan troglodytes) communities, we show that chimpanzees exhibit greater behavioural diversity in environments with more variability - in both recent and historical timescales. Notably, distance from Pleistocene forest refugia is associated with the presence of a larger number of behavioural traits, including both tool and non-tool use behaviours. Since more than half of the behaviours investigated are also likely to be cultural, we suggest that environmental variability was a critical evolutionary force promoting the behavioural, as well as cultural diversification of great apes.

Human impact erodes chimpanzee behavioral diversity.

Chimpanzees possess a large number of behavioral and cultural traits among nonhuman species. The "disturbance hypothesis" predicts that human impact depletes resources and disrupts social learning processes necessary for behavioral and cultural transmission. We used a dataset of 144 chimpanzee communities, with information on 31 behaviors, to show that chimpanzees inhabiting areas with high human impact have a mean probability of occurrence reduced by 88%, across all behaviors, compared to low-impact areas. This behavioral diversity loss was evident irrespective of the grouping or categorization of behaviors. Therefore, human impact may not only be associated with the loss of populations and genetic diversity, but also affects how animals behave. Our results support the view that "culturally significant units" should be integrated into wildlife conservation.

A feasibility study of continuing dose-reduced warfarin for invasive procedures in patients with high thromboembolic risk.

BACKGROUND: The management of perioperative anticoagulation therapy for patients having a high risk of thromboembolism who are receiving long-term oral anticoagulant therapy is uncertain. The prevalent approach is to discontinue oral anticoagulation therapy and initiate heparin therapy. Another potential strategy is to continue oral anticoagulation therapy with a temporary adjustment of warfarin intensity to a preoperative international normalized ratio (INR) of 1.5 to 2.0. Such moderate-dose anticoagulation therapy with warfarin has been shown to be hemostatically safe yet effective in the prevention of thromboembolism after hip or knee replacement. METHODS: Over an 11-year period (ie, 1993 to 2003), our hemostatic consultative service prospectively identified 100 consecutive patients for whom we continued warfarin therapy at adjusted doses during the perioperative period, targeting a goal for the INR of 1.5 to 2.0. Patients were assigned a score for venous thromboembolic risk as well as overall surgical risk using published instruments. Score assignment was based on what was deemed to be extremely high risk for thromboembolism in patients who were receiving long-term warfarin therapy. Although the patients were accrued prospectively, the final retrospective analysis was made after all patients were treated. RESULTS: The most common indication (62%) for high-risk assignment was a thromboembolic event within the past 6 months. The second most prevalent reason was prior postoperative venous thromboembolism (VTE) [11%]. Indications for long-term anticoagulation therapy were recent VTE (62%), inherited thrombophilia (7%), antiphospholipid syndrome (13%), mechanical heart valves (18%), and prior cerebrovascular accident (4%). The prevalence of inherited thrombophilia probably has been grossly underestimated, as neither factor V Leiden mutation nor prothrombin 20210 mutation had been described during the bulk of the accrual time. Most surgical procedures (58%) were significantly invasive (Johns Hopkins category 3 to 5). The mean INR values were 2.1 on the day prior to surgery (SD, 0.9594; range, 1.2 to 6.5; n = 65), 1.8 on the day of surgery (SD, 0.4899; range, 1.2 to 4.9; n = 75), and 1.8 on the first postoperative day (SD, 0.4436; range, 1.1 to 3.3; n = 70). Two patients had major bleeding, and four patients had minor bleeding. One patient developed deep venous thrombosis. Several weeks after surgery, one patient with a prosthetic heart valve died from an embolic stroke, which was associated with a failure to increase his anticoagulation to therapeutic levels. CONCLUSIONS: Moderate-intensity anticoagulant therapy with warfarin, targeting a goal INR of 1.5 to 2.0, appears to be a safe and feasible method for preventing thromboembolic complications in high-risk surgical patients who are receiving long-term oral anticoagulant therapy. This may be considered a reasonable method to afford thromboprophylaxis in highly selected patients who are occasionally seen in clinical practice. This observational study does not prove equality, let alone superiority, to other proposed methods of anticoagulation therapy.

Program director opinions of core competencies in hand surgery training: analysis of differences between plastic and orthopedic surgery accredited programs.

BACKGROUND: The authors' aim was to conduct a national survey of hand surgery fellowship program directors to determine differences of opinions of essential components of hand surgery training between program directors from plastic and orthopedic surgery programs. METHODS: The authors performed a Web-based survey of 74 program directors from all Accreditation Council for Graduate Medical Education-accredited hand surgery fellowship programs to determine components that are essential for hand surgery training. The survey included assessment of nine general areas of practice, 97 knowledge topics, and 172 procedures. Twenty-seven scales of related survey items were created to determine differences between specialty groups based on clinical themes. RESULTS: An 84 percent response rate was achieved, including 49 orthopedic and 12 plastic surgery program directors. There were significant differences in mean responses between the specialty groups in 11 of 27 scales. Only one scale, forearm fractures, contained items with a significantly stronger preference for essential rating among orthopedic surgeons. The other 10 scales contained items with a significantly higher preference for essential rating among plastic surgeons, most of which related to soft-tissue injury and reconstruction. The burn scale had the greatest discrepancy in opinion of essential ratings between the groups, followed by pedicled and free tissue transfer, and amputation and fingertip injuries. CONCLUSIONS: Despite being united under the subspecialty of hand surgery, program directors tend to emphasize clinical areas that are stressed in their respective primary disciplines. These differences promote the advantage of programs that provide exposure to both plastic surgery-trained and orthopedic surgery-trained hand surgeons.

Gaps in exposure to essential competencies in hand surgery fellowship training: a national survey of program directors.

BACKGROUND: Graduate medical education has moved towards competency-based training. The aim of this study was to assess hand surgery program directors' opinions of exposure gaps in core competencies rated as essential for hand surgery training. METHODS: We surveyed the 74 ACGME hand surgery fellowship program directors. Respondents rated their opinion of 9 general areas of practice, 97 knowledge topics, and 172 procedures into one of three categories: essential, exposure needed, or unnecessary. Program directors also rated trainee exposure of each component at their respective program. Moderate and large exposure gaps were respectively defined as presence of at least 25 and 50 % of programs rating trainees as not having proficiency in the component at the end of training. RESULTS: Sixty-two of 74 program directors (84 %) responded to the survey. For the 76 knowledge topics and 98 procedures rated as essential, a majority of the knowledge topics (61 %; n = 46) and procedures (72 %; n = 71) had at least a moderate exposure gap. In addition, 22 % (n = 17) of the essential knowledge topics and 26 % (n = 25) of the essential procedures had a large exposure gap. CONCLUSION: This study illuminates the discrepancies between what is believed to be important for practicing hand surgeons and graduates' proficiency as perceived by program directors. The field of hand surgery must work to determine if program directors have unrealistic expectations for what is essential for practicing hand surgeons or if reforms are needed to improve exposure to essential skills in hand surgery training.

Medical decision-making among adolescents with neonatal brachial plexus palsy and their families: a qualitative study.

BACKGROUND: Elective surgical management of neonatal brachial plexus palsy is complex, variable, and often individualized. Little is known about the medical decision-making process among adolescents with neonatal brachial plexus palsy and their families when faced with making complex treatment decisions. The experiences of these patients and their parents were analyzed to identify key factors in the decision-making process. METHODS: Eighteen adolescents with residual neonatal brachial plexus palsy deficits between 10 and 17 years and their parents were included. Qualitative research design was used involving separate, 1-hour, in person, semistructured interviews, which were audio recorded and transcribed. Grounded theory was applied by two members of the research team to identify recurrent themes and create a codebook that was applied to the data. RESULTS: Medical decision-making among adolescents with neonatal brachial plexus palsy and their families is multifaceted and individualized, composed of both patient- and system-dependent factors. Four codes were identified: (1) knowledge acquisition, (2) multidisciplinary care, (3) adolescent autonomy, and (4) patient expectations and treatment desires. Overall, parental decision-making was heavily influenced by system-dependent factors, whereas adolescents largely based their decisions on individual treatment desires to improve function and/or aesthetics. CONCLUSIONS: There are many areas for improving the delivery of information and health care organization among adolescents with neonatal brachial plexus palsy and their families. The authors recommend the development of educational interdisciplinary programs and decision aids containing evidence-based management guidelines targeted toward primary care providers and patients. The authors believe that a computer-based learning module may provide the best avenue to achieve maximum penetrance and convenience of information sharing. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

A systematic review of peer review for scientific manuscripts.

BACKGROUND: The usefulness of peer review has been expressed as a method to improve the quality of published work. However, there has been a lack of systematic reviews to date to highlight the essential themes of the peer-review process. METHODS: We performed a search of the English language literature published prior to October 2011 using PubMed to identify articles regarding peer review. Inclusion and exclusion criteria were developed a priori. Data were extracted and then analyzed for the prevalence of peer-review themes contained within the literature. RESULTS: Of the 941 articles found during our original literature search, 37 were selected for review. The majority were commentary/editorial articles. The themes in our search included the structure and process of the peer-review system, the criteria for papers, ethics, and the different forms of the peer-review process. CONCLUSIONS: The criteria for submission will vary, but our systematic review provides a comprehensive overview of what reviewers expect from authors. Our systematic review also highlighted ethical considerations for both authors and reviewers during the peer-review process. Although the topic of peer review is expansive and its process may vary from journal to journal, the understanding of the themes outlined in this paper will help authors recognize how to write a more successful paper. Also, more research must be carried out to establish the efficacy of the different styles of peer review, and it would be presumptuous to draw conclusions until further research is established.

Measuring treatment effectiveness: a guide to incorporating the principles of evidence-based medicine.

Every year, hundreds of new surgical devices and techniques are introduced, and plastic surgeons must determine the associated risks, benefits, and costs of these options when incorporating these advances into their armamentarium. This article will discuss the elements of treatment effectiveness by applying the principles of evidence-based medicine to therapeutics. Current efforts to measure plastic surgery outcomes are evolving and rely on case series and retrospective cohort studies. This review will highlight the basic evidence-based medicine concepts and how they can potentially be applied to understand best practices in plastic surgery.

A phase II trial of neoadjuvant capecitabine combined with hyperfractionated accelerated radiation therapy in locally advanced rectal cancer.

OBJECTIVE: Preoperative treatment of rectal cancer with combined chemotherapy and radiation therapy has become a widely accepted strategy. The current challenge is to improve outcomes whereas minimizing morbidity and maximizing the potential for a sphincter sparing procedure. This study sought to evaluate the safety and efficacy of a combination of 2 novel approaches-accelerated, hyperfractionated radiation therapy and twice daily oral capecitabine. METHODS: Consenting patients with locally advanced T3-T4, N0-1, M0 rectal adenocarcinoma, located no further than 15 cm from the anal verge, were treated with twice daily fractions of 1.2 Gy M-F to a total of 50.4 Gy for T3 lesions and 55.2 Gy for T4 lesions. Concomitantly, the patients received capecitabine 825 mg/m twice per day 7 days per week. Patients were operated on 4 to 6 weeks after completion of therapy. RESULTS: Sixteen of 17 enrolled patients were eligible and all 16 completed the full course of treatment including definitive surgery. Eleven patients had a sphincter sparing procedure and 5 had an abdominoperineal resection. Tumor and/or nodal downstaging occurred in 81% of patients, 100% of resections were R0, and the sphincter preservation rate was 68%. There were 18% pathologic complete remissions and 68% of specimens were node negative with an additional 12% Nx owing to transanal excision. The therapy was well tolerated and there were no unexpected toxicities with only diarrhea reaching grade 3 in 4 patients. CONCLUSIONS: This novel approach to preoperative treatment of rectal adenocarcinoma was well tolerated and effective. Comparison with more established approaches appears justified.

A phase II study of gemcitabine in patients with relapsed or refractory low-grade non-Hodgkin lymphoma.

PURPOSE: The purpose of this study was to determine the tolerability, clinical response rate, and time to disease progression of gemcitabine treatment in patients with low-grade non-Hodgkin lymphoma. (NHL) PATIENTS AND METHODS: Twenty patients with low-grade NHL and progression of disease after at least 1 prior treatment regimen were prospectively enrolled. The treatment regimen consisted of 1200 mg/m2 gemcitabine intravenously administered weekly for 7 weeks followed by a 1-week rest. Subsequent treatment was given weekly for 3 weeks followed by a 1-week rest and repeated for a maximal treatment of 6 cycles until disease progression or unacceptable toxicity. RESULTS: The predominant histologic subtypes among our patients were small lymphocytic (8 of 20) and follicular (7 of 20). Grade III/IV hematologic toxicity was observed in 15 of 20 patients and dose reductions or treatment delays occurred in 19 of 20 patients. Fatigue and asthenia were treatment-limiting in many patients. There were no complete or partial responses observed and only 2 patients had stable disease after 12 weeks of treatment. The average time to progression or off-study status was 2.3 months (95% confidence interval, 1.7-2.9) with 8 patients showing progression of disease. Twelve patients were taken off the study as a result of unacceptable toxicity before observed progression of disease. No patient completed the planned course of therapy. With a median follow up of 10.2 months, 10 of 20 patients remained alive. CONCLUSION: Gemcitabine as a single agent, in this dosage and schedule, has minimal clinical activity in relapsed or refractory low-grade lymphomas and was associated with considerable toxicity. Therefore, further study of gemcitabine in this setting is not justified.