No Time for Time from No-Time

Programs in quantum gravity often claim that time emerges from fundamentally timeless physics. In the semiclassical time program time arises only after approximations are taken. Here we ask what justifies taking these approximations and show that time seems to sneak in when answering this question. This raises the worry that the approach is either unjustified or circular in deriving time from no-time.Comment: Presented at Philosophy of Science Association 2021 meetin

No Time for Time from No-Time

Programs in quantum gravity often claim that time emerges from fundamentally timeless physics. In the semiclassical time program time arises only after approx- imations are taken. Here we ask what justifies taking these approximations and show that time seems to sneak in when answering this question. This raises the worry that the approach is either unjustified or circular in deriving time from no–time

Evidence for variable selective pressures at MC1R

It is widely assumed that genes that influence variation in skin and hair pigmentation are under selection. To date,the melanocortin 1 receptor (MC1R) is the only gene identified that explains substantial phenotypic variance inhuman pigmentation. Here we investigate MC1R polymorphism in several populations, for evidence of selection.We conclude that MC1R is under strong functional constraint in Africa, where any diversion from eumelanin production (black pigmentation) appears to be evolutionarily deleterious. Although many of the MC1R amino acid variants observed in non-African populations do affect MC1R function and contribute to high levels of MC1R diversity in Europeans, we found no evidence, in either the magnitude or the patterns of diversity, for its enhancement by selection; rather, our analyses show that levels of MC1R polymorphism simply reflect neutral expectations underrelaxation of strong functional constraint outside Africa

Once and Future Gulf of Mexico Ecosystem: Restoration Recommendations of an Expert Working Group

The Deepwater Horizon (DWH) well blowout released more petroleum hydrocarbons into the marine environment than any previous U.S. oil spill (4.9 million barrels), fouling marine life, damaging deep sea and shoreline habitats and causing closures of economically valuable fisheries in the Gulf of Mexico. A suite of pollutants—liquid and gaseous petroleum compounds plus chemical dispersants—poured into ecosystems that had already been stressed by overfishing, development and global climate change. Beyond the direct effects that were captured in dramatic photographs of oiled birds in the media, it is likely that there are subtle, delayed, indirect and potentially synergistic impacts of these widely dispersed, highly bioavailable and toxic hydrocarbons and chemical dispersants on marine life from pelicans to salt marsh grasses and to deep-sea animals. As tragic as the DWH blowout was, it has stimulated public interest in protecting this economically, socially and environmentally critical region. The 2010 Mabus Report, commissioned by President Barack Obama and written by the secretary of the Navy, provides a blueprint for restoring the Gulf that is bold, visionary and strategic. It is clear that we need not only to repair the damage left behind by the oil but also to go well beyond that to restore the anthropogenically stressed and declining Gulf ecosystems to prosperity-sustaining levels of historic productivity. For this report, we assembled a team of leading scientists with expertise in coastal and marine ecosystems and with experience in their restoration to identify strategies and specific actions that will revitalize and sustain the Gulf coastal economy. Because the DWH spill intervened in ecosystems that are intimately interconnected and already under stress, and will remain stressed from global climate change, we argue that restoration of the Gulf must go beyond the traditional "in-place, in-kind" restoration approach that targets specific damaged habitats or species. A sustainable restoration of the Gulf of Mexico after DWH must: 1. Recognize that ecosystem resilience has been compromised by multiple human interventions predating the DWH spill; 2. Acknowledge that significant future environmental change is inevitable and must be factored into restoration plans and actions for them to be durable; 3. Treat the Gulf as a complex and interconnected network of ecosystems from shoreline to deep sea; and 4. Recognize that human and ecosystem productivity in the Gulf are interdependent, and that human needs from and effects on the Gulf must be integral to restoration planning. With these principles in mind, the authors provide the scientific basis for a sustainable restoration program along three themes: 1. Assess and repair damage from DWH and other stresses on the Gulf; 2. Protect existing habitats and populations; and 3. Integrate sustainable human use with ecological processes in the Gulf of Mexico. Under these themes, 15 historically informed, adaptive, ecosystem-based restoration actions are presented to recover Gulf resources and rebuild the resilience of its ecosystem. The vision that guides our recommendations fundamentally imbeds the restoration actions within the context of the changing environment so as to achieve resilience of resources, human communities and the economy into the indefinite future

A Once and Future Gulf of Mexico Ecosystem: Restoration Recommendations of an Expert Working Group

The Deepwater Horizon (DWH) well blowout released more petroleum hydrocarbons into the marine environment than any previous U.S. oil spill (4.9 million barrels), fouling marine life, damaging deep sea and shoreline habitats and causing closures of economically valuable fisheries in the Gulf of Mexico. A suite of pollutants — liquid and gaseous petroleum compounds plus chemical dispersants — poured into ecosystems that had already been stressed by overfishing, development and global climate change. Beyond the direct effects that were captured in dramatic photographs of oiled birds in the media, it is likely that there are subtle, delayed, indirect and potentially synergistic impacts of these widely dispersed, highly bioavailable and toxic hydrocarbons and chemical dispersants on marine life from pelicans to salt marsh grasses and to deep-sea animals. As tragic as the DWH blowout was, it has stimulated public interest in protecting this economically, socially and environmentally critical region. The 2010 Mabus Report, commissioned by President Barack Obama and written by the secretary of the Navy, provides a blueprint for restoring the Gulf that is bold, visionary and strategic. It is clear that we need not only to repair the damage left behind by the oil but also to go well beyond that to restore the anthropogenically stressed and declining Gulf ecosystems to prosperity-sustaining levels of historic productivity. For this report, we assembled a team of leading scientists with expertise in coastal and marine ecosystems and with experience in their restoration to identify strategies and specific actions that will revitalize and sustain the Gulf coastal economy. Because the DWH spill intervened in ecosystems that are intimately interconnected and already under stress, and will remain stressed from global climate change, we argue that restoration of the Gulf must go beyond the traditional “in-place, in-kind” restoration approach that targets specific damaged habitats or species. A sustainable restoration of the Gulf of Mexico after DWH must: 1. Recognize that ecosystem resilience has been compromised by multiple human interventions predating the DWH spill; 2. Acknowledge that significant future environmental change is inevitable and must be factored into restoration plans and actions for them to be durable; 3. Treat the Gulf as a complex and interconnected network of ecosystems from shoreline to deep sea; and 4. Recognize that human and ecosystem productivity in the Gulf are interdependent, and that human needs from and effects on the Gulf must be integral to restoration planning. With these principles in mind, we provide the scientific basis for a sustainable restoration program along three themes: 1. Assess and repair damage from DWH and other stresses on the Gulf; 2. Protect existing habitats and populations; and 3. Integrate sustainable human use with ecological processes in the Gulf of Mexico. Under these themes, 15 historically informed, adaptive, ecosystem-based restoration actions are presented to recover Gulf resources and rebuild the resilience of its ecosystem. The vision that guides our recommendations fundamentally imbeds the restoration actions within the context of the changing environment so as to achieve resilience of resources, human communities and the economy into the indefinite future

"A calorie is a calorie" violates the second law of thermodynamics

The principle of "a calorie is a calorie," that weight change in hypocaloric diets is independent of macronutrient composition, is widely held in the popular and technical literature, and is frequently justified by appeal to the laws of thermodynamics. We review here some aspects of thermodynamics that bear on weight loss and the effect of macronutrient composition. The focus is the so-called metabolic advantage in low-carbohydrate diets – greater weight loss compared to isocaloric diets of different composition. Two laws of thermodynamics are relevant to the systems considered in nutrition and, whereas the first law is a conservation (of energy) law, the second is a dissipation law: something (negative entropy) is lost and therefore balance is not to be expected in diet interventions. Here, we propose that a misunderstanding of the second law accounts for the controversy about the role of macronutrient effect on weight loss and we review some aspects of elementary thermodynamics. We use data in the literature to show that thermogenesis is sufficient to predict metabolic advantage. Whereas homeostasis ensures balance under many conditions, as a general principle, "a calorie is a calorie" violates the second law of thermodynamics

Academic Cancer Center Phase I Program Development

Multiple factors critical to the effectiveness of academic phase I cancer programs were assessed among 16 academic centers in the U.S. Successful cancer centers were defined as having broad phase I and I/II clinical trial portfolios, multiple investigator‐initiated studies, and correlative science. The most significant elements were institutional philanthropic support, experienced clinical research managers, robust institutional basic research, institutional administrative efforts to reduce bureaucratic regulatory delays, phase I navigators to inform patients and physicians of new studies, and a large cancer center patient base. New programs may benefit from a separate stand‐alone operation, but mature phase I programs work well when many of the activities are transferred to disease‐oriented teams. The metrics may be useful as a rubric for new and established academic phase I programs.This commentary assesses the factors necessary for the effectiveness of academic phase I cancer programs. The metrics presented here may be useful as a rubric for new and established programs.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139928/1/onco12106-sup-0001-suppinfo1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139928/2/onco12106.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139928/3/onco12106-sup-0002-suppinfo2.pd

Association of ACTN3 R577X but not ACE I/D gene variants with elite rugby union player status and playing position

We aimed to quantify the ACE I/D and ACTN3 R577X (rs1815739) genetic variants in elite rugby athletes (rugby union and league), compare genotype frequencies to controls and between playing positions. The rugby athlete cohort consisted of 507 Caucasian men, including 431 rugby union athletes that for some analyses were divided into backs and forwards and into specific positional groups: front five, back row, half backs, centers and back three. Controls were 710 Caucasian men and women. Real-time PCR of genomic DNA was used to determine genotypes using TaqMan probes and groups were compared using Chi-square and odds ratio (OR) statistics. Correction of p-values for multiple comparisons was according to Benjamini-Hochberg. There was no difference in ACE I/D genotype between groups. ACTN3 XX genotype tended to be underrepresented in rugby union backs (15.7%) compared to forwards (24.8%; P=0.06). Interestingly, the 69 back three players (wings and full backs) in rugby union included only six XX genotype individuals (8.7%), with the R allele more common in the back three (68.8%) than controls (58.0%; χ2=6.672, P=0.04; OR=1.60) and forwards (47.5%; χ2=11.768, P=0.01; OR=2.00). Association of ACTN3 R577X with playing position in elite rugby union athletes suggests inherited fatigue resistance is more prevalent in forwards while inherited sprint ability is more prevalent in backs, especially wings and full backs. These results also demonstrate the advantage of focusing genetic studies on a large cohort within a single sport, especially when intra-sport positional differences exist, instead of combining several sports with varied demands and athlete characteristics

Self-directed learning of basic musculoskeletal ultrasound among rheumatologists in the United States

Objective Because musculoskeletal ultrasound (MSUS) is highly user dependent, we aimed to establish whether non-mentored learning of MSUS is sufficient to achieve the same level of diagnostic accuracy and scanning reliability as has been achieved by rheumatologists recognized as international experts in MSUS. Methods A group of 8 rheumatologists with more experience in MSUS and 8 rheumatologists with less experience in MSUS participated in an MSUS exercise to assess patients with musculoskeletal abnormalities commonly seen in a rheumatology practice. Patients' established diagnoses were obtained from chart review (gout, osteoarthritis, rotator cuff syndrome, rheumatoid arthritis, and seronegative arthritis). Two examining groups were formed, each composed of 4 less experienced and 4 more experienced examiners. Each group scanned 1 predefined body region (hand, wrist, elbow, shoulder, knee, or ankle) in each of 8 patients, blinded to medical history and physical examination. Structural abnormalities were noted with dichotomous answers, and an open-ended answer was used for the final diagnosis. Results Less experienced and more experienced examiners achieved the same diagnostic accuracy (US-established diagnosis versus chart review diagnosis). The interrater reliability for tissue pathology was slightly higher for more experienced versus less experienced examiners (Κ = 0.43 versus Κ = 0.34; P = 0.001). Conclusion Non-mentored training in MSUS can lead to the achievement of diagnostic accuracy in MSUS comparable to that achieved by highly experienced international experts. Reliability may increase slightly with additional experience. Further study is needed to determine the minimal training requirement to achieve proficiency in MSUS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65036/1/20063_ftp.pd