Projecting marine mammal distribution in a changing climate

Climate-related shifts in marine mammal range and distribution have been observed in some populations; however, the nature and magnitude of future responses are uncertain in novel environments projected under climate change. This poses a challenge for agencies charged with management and conservation of these species. Specialized diets, restricted ranges, or reliance on specific substrates or sites (e.g., for pupping) make many marine mammal populations particularly vulnerable to climate change. High-latitude, predominantly ice-obligate, species have experienced some of the largest changes in habitat and distribution and these are expected to continue. Efforts to predict and project marine mammal distributions to date have emphasized data-driven statistical habitat models. These have proven successful for short time-scale (e.g., seasonal) management activities, but confidence that such relationships will hold for multi-decade projections and novel environments is limited. Recent advances in mechanistic modeling of marine mammals (i.e., models that rely on robust physiological and ecological principles expected to hold under climate change) may address this limitation. The success of such approaches rests on continued advances in marine mammal ecology, behavior, and physiology together with improved regional climate projections. The broad scope of this challenge suggests initial priorities be placed on vulnerable species or populations (those already experiencing declines or projected to undergo ecological shifts resulting from climate changes that are consistent across climate projections) and species or populations for which ample data already exist (with the hope that these may inform climate change sensitivities in less well observed species or populations elsewhere). The sustained monitoring networks, novel observations, and modeling advances required to more confidently project marine mammal distributions in a changing climate will ultimately benefit management decisions across time-scales, further promoting the resilience of marine mammal populations

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Rhinoplasty Education Using a Standardized Patient Encounter

Background Comprehensive aesthetic surgery training continues to be a challenge for residency programs. Our residency program developed a rhinoplasty-based objective structured clinical examination (OSCE) based upon validated methods as part of the residency education curriculum. We report our experience with the rhinoplasty-based OSCE and offer guidance to its incorporation within residency programs. Methods The encounter involved resident evaluation and operative planning for a standardized patient desiring a rhinoplasty procedure. Validated OSCE methods currently used at our medical school were implemented. Residents were evaluated on appropriate history taking, physical examination, and explanation to the patient of treatment options. Examination results were evaluated using analysis of variance (statistical significance P<0.05). Results Twelve residents completed the rhinoplasty OSCE. Medical knowledge assessment showed increasing performance with clinical year, 50% versus 84% for postgraduate year 3 and 6, respectively (P<0.005). Systems-based practice scores showed that all residents incorrectly submitted forms for billing and operative scheduling. All residents confirmed that the OSCE realistically represents an actual patient encounter. All faculty confirmed the utility of evaluating resident performance during the OSCE as a useful assessment tool for determining the Next Accreditation System Milestone level. Conclusions Aesthetic surgery training for residents will require innovative methods for education. Our examination showed a program-educational weakness in billing/coding, an area that will be improved upon by topic-specific lectures. A thoroughly developed OSCE can provide a realistic educational opportunity to improve residents' performance on the nonoperative aspects of rhinoplasty and should be considered as an adjunct to resident education

Orthopaedic outcomes of prenatal versus postnatal repair of myelomeningocele

BACKGROUND: Myelomeningocele is the most common form of spina bifida and is characterized by extrusion of the spinal cord through a spinal canal defect. It often results in lifelong disability and significant orthopaedic issues such as spinal deformity, hip abnormalities, and clubfoot. A randomized controlled trial has shown efficacy of prenatal repair in decreasing the need for shunting and improving motor outcomes. However, no studies have evaluated the effects of prenatal repair on orthopaedic outcomes. The purpose of this study was to determine the rates of orthopaedic conditions in patients with prenatal and postnatal repair of myelomeningocele, as well as compare the rates of treatment required for orthopaedic conditions. METHODS: This study analyzes the relevant outcomes from a prospective randomized controlled trial (Management of Myelomeningocele Study, MOMS). Eligible women were randomized to prenatal or postnatal repair, and patients were evaluated prospectively. Outcomes of interest included rates of scoliosis, kyphosis, hip abnormality, clubfoot, tibial torsion, and leg length discrepancy at 12 months and 30 months. Additionally, we evaluated the need for orthopaedic intervention, notably casting and bracing at the same time points. Statistical analyses included descriptive statistics and univariate analyses. RESULTS: The data for the full cohort of 183 patients was analyzed (91 prenatal, 92 postnatal). Patient demographics have been previously described by the MOMS investigators. There were no differences in the rates of scoliosis, kyphosis, hip abnormality, clubfoot or tibial torsion between patients treated with prenatal or postnatal repair. However, the rate of leg length discrepancy was lower in the prenatal repair group at 12 months and 30 months (7% vs. 16% at 30 months, p = 0.047). In addition, the rates of patients requiring casting or bracing was significantly lower in patients treated with prenatal repair at 12 months and 30 months (78% vs. 90% at 30 months, p = 0.036). CONCLUSION: Patients that are treated with prenatal repair of myelomeningocele may develop milder forms of orthopaedic conditions and may not require extensive orthopaedic management

Orthopaedic outcomes of prenatal versus postnatal repair of myelomeningocele

Myelomeningocele, characterized by extrusion of the spinal cord through a spinal canal defect, is the most common form of spina bifida, often resulting in lifelong disability and significant orthopaedic issues. A randomized controlled trial (RCT) has shown the efficacy of prenatal repair in decreasing the need for shunting and improving motor outcomes. However, no studies have evaluated the effects of prenatal repair on orthopaedic outcomes. The purpose of this study was to determine the rates of orthopaedic conditions in patients with prenatal and postnatal repair of myelomeningocele and compare the rates of treatment required. This study analyzes the relevant outcomes from a prospective RCT (Management of Myelomeningocele Study). Eligible women were randomized to prenatal or postnatal repair, and patients were evaluated prospectively. Outcomes of interest included rates of scoliosis, kyphosis, hip abnormality, clubfoot, tibial torsion, and leg length discrepancy (LLD) at 12 and 30 months. The need for orthopaedic intervention at the same time points was also evaluated. Statistical analyses included descriptive statistics and univariate analyses. Data for the full cohort of 183 patients were analyzed (91 prenatal, 92 postnatal). There were no differences in rates of scoliosis, kyphosis, hip abnormality, clubfoot or tibial torsion between patients treated with prenatal or postnatal repair. The rate of LLD was lower in the prenatal repair group at 12 and 30 months (7 vs. 16% at 30 months, P = 0.047). The rates of patients requiring casting or bracing were significantly lower in patients treated with prenatal repair at 12 and 30 months (78 vs. 90% at 30 months, P = 0.036). Patients treated with prenatal myelomeningocele repair may develop milder forms of orthopaedic conditions and may not require extensive orthopaedic management

Preferred leadership prototypes of male and female leaders in 27 countries

Our study shows that preferred leadership prototypes held by female leaders differ from the prototypes held by male leaders, and that these prototype differences vary across countries, cultures, and especially industries. In general, female managers prefer participative, team oriented, and charismatic leadership prototype dimensions more than males. Contrary to popular belief, both males and females valued humane-oriented leadership equally. Gender egalitarianism and industry type were important moderators of the gender–leadership prototype relationship. Gender egalitarianism increased females' desire for participative leadership, while prototype differences between genders were magnified in the finance and food industries.

Centrifugal and Biochemical-comparison of Proteoglycan Aggregates Horn Articular-cartilage in Experimental Joint Disuse and Joint Instability

Two models involving altered joint loading were compared with regard to their effects on the biochemical composition and proteoglycan aggregate structure of articular cartilage. Disuse atrophy was created in greyhound dogs by nonrigid immobilization of the right knee in 90 degrees of flexion, and joint instability was created by transection of the anterior cruciate ligament. Similarities and differences between the two experimental groups at two different time periods were examined to investigate why joint instability induces progressive and irreversible changes to the articular cartilage, whereas joint disuse induces changes that may be reversible when the joint is remobilized. The following studies were performed on the cartilage from all experimental and control groups: (a) compositional analyses to determine water, uronate, and hydroxyproline contents; (b) high performance liquid chromatography for detection of hyaluronan and chondroitin sulfates; and (c) centrifugation analyses of nondissociatively extracted and purified proteoglycans to isolate and quantify the populations of monomers and slow and fast-sedimenting families of aggregates. In general, all cartilage was found to have a decreased ratio of proteoglycan to collagen after 4 weeks of disuse, and this ratio returned to control values at 8 weeks. In contrast, cartilage had an elevated ratio of proteoglycan to collagen as well as increased hydration at 12 weeks after transection of the anterior cruciate ligament. The most striking contrast between the two models was the finding of an approximately 80% decrease in the content of hyaluronan at both time periods after transection of the anterior cruciate ligament, with no evidence of a change after disuse. The results of centrifugation analyses indicated a significant decrease in the quantity of proteoglycan aggregates in both models. However, this decrease was associated primarily with a loss of slow-sedimenting aggregates after disuse and a loss of both slow and fast-sedimenting aggregates after transection of the anterior cruciate ligament. Furthermore, the population of fast-sedimenting aggregates was depleted to a greater extent than that of the slow-sedimenting aggregates. The preservation of fast-sedimenting aggregates as well as hyaluronan after periods of joint disuse but not joint instability suggests a possible mechanism for the reversibility of cartilage changes. Although the proteoglycan aggregates were depleted after disuse atrophy, it is possible that an aggregate-depleted matrix could recover when normal proteoglycan synthesis is resumed. In contrast, although synthesis may be maintained or elevated after transection of the anterior cruciate ligament, the matrix may not be repopulated with aggregates because there is an insufficient amount of hyaluronan