Introduction to the Special Issue: Genome-Wide Association Studies

Introduction to the Special Issue: Genome-Wide Association StudiesComment: Published in at http://dx.doi.org/10.1214/09-STS310 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Variability in the reported management of pulmonary metastases in osteosarcoma.

Nearly 20% of patients with newly diagnosed osteosarcoma have detectable metastases at diagnosis; the majority of which occur in the lungs. There are no established recommendations for the timing and modality of metastasectomy. Members of the Connective Tissue Oncology Society (CTOS) were emailed an anonymous 10-min survey assessing their management practices for pulmonary findings at the time of an osteosarcoma diagnosis. The questionnaire presented three scenarios and discussed the choice to perform surgery, the timing of resection, and the choice of surgical procedure. Analyses were stratified by medical profession. One hundred and eighty-three physicians responded to our questionnaire. Respondents were comprised of orthopedic surgeons (37%), medical oncologists (31%), pediatric oncologists (22%), and other medical subspecialties (10%). There was variability among the respondents in the management of the pulmonary nodules. The majority of physicians chose to resect the pulmonary nodules following neoadjuvant chemotherapy (46-63%). Thoracotomy was the preferred technique for surgical resection. When only unilateral findings were present, the majority of physicians did not explore the contralateral lung. The majority of respondents did not recommend resection if the pulmonary nodule disappeared following chemotherapy. The survey demonstrated heterogeneity in the management of pulmonary metastases in osteosarcoma. Prospective trials need to evaluate whether these differences in management have implications for outcomes for patients with metastatic osteosarcoma

Bone Loss During Spaceflight: Available Models and Counter-Measures

There is ongoing concern for human health during spaceflights. Of particular interest is the uncoupling of bone remodeling and its resultant effect on calcium metabolism and bone loss. The calculated average loss of bone mineral density (BMD) is approximately 1-1.5% per month of spaceflight. The effect of decreased BMD on associated fractures in astronauts is not known. Currently on the International Space Station (ISS), bone loss is managed through dietary supplements and modifications and resistance exercise regimen. As the duration of space flights increases, a review of the current methods available for the prevention of bone loss is warranted. The goal of this project is to review and summarize recent studies that have focused on maintaining BMD during exposure to microgravity. Interventions were divided into physical (Table 1), nutritional (Table 2), or pharmacologic (Table 3) categories. Physical modalities included resistance exercise, low level vibration, and low intensity pulsed ultrasound. Nutritional interventions included altering protein, salt, and fat intake; and vitamin D supplementation. Pharmacologic interventions included the use of bisphosphonates and beta blockers. Studies reported outcomes based on bone density determined by DXA bone scan, micro-architecture of histology and microCT, and serum and urine markers of bone turnover. The ground analog models utilized to approximate osseous physiology in microgravity included human patients previously paralyzed or subjects confined to bedrest. Ground analog animal models include paralysis, immobilization and ovariectomies. As a result of the extensive research performed there is a multi-modality approach available for the management of BMD during spaceflight that includes resistance training, nutrition and dietary supplements. However, there is a paucity of literature describing a formalized tiered protocol to guide investigators through the progression from animal models to human patient ground analogs to experiments on the ISS. With regards to testing, further evaluation to determine the association between non-invasive tests and fracture during and after spaceflight needs to be performed

Use of Placebo in Supplementation Studies-Vitamin D Research Illustrates an Ethical Quandary.

History has shown that without explicit and enforced guidelines, even well-intentioned researchers can fail to adequately examine the ethical pros and cons of study design choices. One area in which consensus does not yet exist is the use of placebo groups in vitamin supplementation studies. As a prime example, we focus on vitamin D research. We aim to provide an overview of the ethical issues in placebo-controlled studies and guide future discussion about the ethical use of placebo groups. Research in the field of vitamin D shows variation in how placebo groups are used. We outline four types of control groups in use: active-control, placebo-control with restrictions on supplementation, placebo-control without supplementation restrictions, and placebo-control with rescue repletion therapy. The first two types highlight discrete ethical issues: active-control trials limit the ability to detect a difference; placebo-control trials that restrict supplementation potentially place subjects at risk of undue harm. The final two, placebo-control without supplementation restrictions or with rescue repletion therapy, offer potential solutions to these ethical challenges. Building on this, guidelines should be established and enforced on the use of placebo in supplementation studies. Furthermore, the field of vitamin D research has the potential to set an example worthy of emulation

Outpatient Commitment: A Competency Based Justification

A recent survey of state statutes for outpatient commitment (Torrey and Kaplan, 1995) indicates that while thirty-five states and the District of Columbia have laws permitting outpatient commitment, Massachusetts is not one of them. Rather, Massachusetts uses a competency-based, substituted-decision-making model for the involuntary administration of medication in the community. To appreciate the Massachusetts model, it is important to understand how this court-ordered involuntary outpatient treatment fits into the overall scheme of outpatient commitment and how it is structured. A review of involuntary outpatient treatment (IOT) literature indicates that it is prudent to distinguish between outpatient commitment, conditional release, and conservatorship-guardianship (Torrey and Kaplan, 1995). Two states whose IOT is based on the guardianship process and is described in the literature are California and New Mexico. Lamb and Weinberger (1992, 1993) have discussed California’s use of guardians for the gravely disabled psychiatric outpatient, and Schneider-Braus (1986) has presented a single case report from New Mexico

Mitochondrial genome rearrangements in the Scleractinia/Corallimorpharia complex: implications for coral phylogeny

Corallimorpharia is a small Order of skeleton-less animals that is closely related to the reef-building corals (Scleractinia) and of fundamental interest in the context of understanding the potential impacts of climate change in the future on coral reefs. The relationship between the nominal Orders Corallimorpharia and Scleractinia is controversial-the former is either the closest outgroup to the Scleractinia or alternatively is derived from corals via skeleton loss. This latter scenario, the "naked coral" hypothesis, is strongly supported by analyses based on mitochondrial (mt) protein sequences, whereas the former is equally strongly supported by analyses of mt nucleotide sequences. The "naked coral" hypothesis seeks to link skeleton loss in the putative ancestor of corallimorpharians with a period of elevated oceanic CO2 during the Cretaceous, leading to the idea that these skeleton-less animals may be harbingers for the fate of coral reefs under global climate change. In an attempt to better understand their evolutionary relationships, we examined mt genome organization in a representative range (12 species, representing 3 of the 4 extant families) of corallimorpharians and compared these patterns with other Hexacorallia. The most surprising finding was that mt genome organization in Corallimorphus profundus, a deep-water species that is the most scleractinian-like of all corallimorpharians on the basis of morphology, was much more similar to the common scleractinian pattern than to those of other corallimorpharians. This finding is consistent with the idea that C. profundus represents a key position in the coral corallimorpharian transition

Molecular diffusion of CF\u3csub\u3e3\u3c/sub\u3eSF\u3csub\u3e5\u3c/sub\u3e in pure water and artificial seawater

We have experimentally determined the diffusion coefficient for trifluoromethyl sulfur pentafluoride (CF3SF5) in pure water and artificial seawater over a temperature range of − 2.0 °C to 30.0 °C. A working gas standard containing known concentrations of CF3SF5 and sulfur hexafluoride (SF6) was prepared. The working standard was allowed to diffuse across a water barrier, stabilized with agar gel, and the diffused gas was swept into a gas chromatograph with an electron-capture detector to measure the resulting gas mixing ratio. The mixing ratios for both CF3SF5 and SF6 were measured to determine the diffusivity for each species. The diffusion coefficient for SF6 was determined during these experiments as a check against existing literature values and to validate our experimental setup. The experimental data were fit to the Arrhenius equation to yield the following equations DCF3SF5 = 0.0015 exp (-12.9/RT) and DSF6 = 0.037 exp (-19.8/RT), where R is the gas constant in units of kilojoules per mole per kelvin and T is the temperature in kelvin. At the mean temperature of the ocean, 18 °C, DCF3SF5 = 7.02 × 10-6 ± 9.9% and DSF6 = 1.03 × 10-5 ± 13.8 % cm2/s. The diffusion coefficients for SF6 matched the literature data within 4.3% for all temperatures

Mitochondrial genome rearrangements in the Scleractinia / Corallimorpharia complex: implications for coral phylogeny

Corallimorpharia is a small Order of skeleton-less animals that is closely related to the reef-building corals (Scleractinia) and of fundamental interest in the context of understanding the potential impacts of climate change in the future on coral reefs. The relationship between the nominal Orders Corallimorpharia and Scleractinia is controversial – the former is either the closest outgroup to the Scleractinia or, alternatively is derived from corals via skeleton loss. This latter scenario, the “naked coral” hypothesis, is strongly supported by analyses based on mitochondrial protein sequences, whereas the former is equally strongly supported by analyses of mitochondrial (mt) nucleotide sequences. The “naked coral” hypothesis seeks to link skeleton loss in the putative ancestor of corallimorpharians with a period of elevated oceanic CO2 during the Cretaceous, leading to the idea that these skeleton-less animals may be harbingers for the fate of coral reefs under global climate change. In an attempt to better understand their evolutionary relationships, we examined mitochondrial genome organization in a representative range (12 species, representing 3 of the 4 extant families) of corallimorpharians and compared these patterns to other Hexacorallia. The most surprising finding was that mt genome organization in Corallimorphus profundus, a deep-water species that is the most scleractinian-like of all corallimorpharians on the basis of morphology, was much more similar to the common scleractinian pattern than to those of other corallimorpharians. This finding is consistent with the idea that C. profundus represents a key position in the coral <-> corallimorpharian transition.São Paulo Research Foundation (FAPESP)São Paulo University Marine Biology Centre (CEBIMar)National Science Council (NSC) and Academia Sinica (Thematic Grants 2005–2010) to C.A.C.Australian Research Council to D.J.M. Cora