Florida Atlantic Coast Telemetry (FACT) Array: A Working Partnership

The Florida Atlantic Coast Telemetry (FACT) Array is a collaborative partnership of researchers from 24 different organizations using passive acoustic telemetry to document site fidelity, habitat preferences, seasonal migration patterns, and reproductive strategies of valuable sportfish, sharks, and marine turtles. FACT partners have found that by bundling resources, they can leverage a smaller investment to track highly mobile animals beyond a study area typically restrained in scale by funds and manpower. FACT is guided by several simple rules: use of the same type of equipment, locate receivers in areas that are beneficial to all researchers when feasible, maintain strong scientific ethics by recognizing that detection data on any receiver belongs to the tag owner, do not use other members detection data without permission and acknowledge FACT in publications. Partners have access to a network of 480 receivers deployed along a continuum of habitats from freshwater rivers to offshore reefs and covers 1100 km of coastline from the Dry Tortugas, Florida to South Carolina and extends to the Bahamas. Presently, 49 species, (25 covered by Fisheries Management Plans and five covered by the Endangered Species Act) have been tagged with 2736 tags in which 1767 tags are still active

Return-to-Play and Competitive Outcomes After Ulnar Collateral Ligament Reconstruction Among Baseball Players: A Systematic Review

Background: Ulnar collateral ligament (UCL) reconstruction (UCLR) is very common in baseball. However, no review has compared the return-to-play (RTP) and in-game performance statistics of pitchers after primary and revision UCLR as well as of position players after UCLR. Purpose: To review, synthesize, and evaluate the published literature on outcomes after UCLR in baseball players to determine RTP and competitive outcomes among various populations of baseball players. Study Design: Systematic review; Level of evidence, 4. Methods: A literature search including studies between 1980 and November 4, 2019, was conducted for articles that included the following terms: ulnar collateral ligament, elbow, medial collateral ligament, Tommy John surgery, throwing athletes, baseball pitchers, biomechanics, and performance. To be included, studies must have evaluated baseball players at any level who underwent UCLR (primary or revision) and assessed RTP and/or competitive outcomes. Results: A total of 29 studies with relatively high methodological quality met the inclusion criteria. After primary UCLR, Major League Baseball (MLB) pitchers returned to play in 80% to 97% of cases in approximately 12 months; however, return to the same level of play (RTSP) was less frequent and took longer, with 67% to 87% of MLB pitchers returning in about 15 months. RTP rates for MLB pitchers after revision UCLR were slightly lower, ranging from 77% to 85%, while RTSP rates ranged from 55% to 78%. RTP rates for catchers (59%-80%) were generally lower than RTP rates for infielders (76%) and outfielders (89%). All studies found a decrease in pitching workloads after UCLR. Fastball usage may also decrease after UCLR. Changes in earned run average and walks plus hits per inning pitched were inconclusive. Conclusion: Pitchers returned to play after UCLR in approximately 12 months and generally took longer to return to their same level of play. Pitchers also returned to play less frequently after revision UCLR. After both primary and revision UCLR, professional pitchers experienced decreased workloads and potentially decreased fastball usage as well. Catchers may RTP after UCLR less frequently than pitchers, infielders, and outfielders possibly because of the frequency of throwing in the position. These results will help guide clinical decision making and patient education when treating UCL tears in baseball players

Effect of Sex and Prior Exposure to a Cafeteria Diet on the Distribution of Sex Hormones between Plasma and Blood Cells

It is generally assumed that steroid hormones are carried in the blood free and/or bound to plasma proteins. We investigated whether blood cells were also able to bind/carry sex-related hormones: estrone, estradiol, DHEA and testosterone. Wistar male and female rats were fed a cafeteria diet for 30 days, which induced overweight. The rats were fed the standard rat diet for 15 additional days to minimize the immediate effects of excess ingested energy. Controls were always kept on standard diet. After the rats were killed, their blood was used for 1) measuring plasma hormone levels, 2) determining the binding of labeled hormones to washed red blood cells (RBC), 3) incubating whole blood with labeled hormones and determining the distribution of label between plasma and packed cells, discounting the trapped plasma volume, 4) determining free plasma hormone using labeled hormones, both through membrane ultrafiltration and dextran-charcoal removal. The results were computed individually for each rat. Cells retained up to 32% estrone, and down to 10% of testosterone, with marked differences due to sex and diet (the latter only for estrogens, not for DHEA and testosterone). Sex and diet also affected the concentrations of all hormones, with no significant diet effects for estradiol and DHEA, but with considerable interaction between both factors. Binding to RBC was non-specific for all hormones. Estrogen distribution in plasma compartments was affected by sex and diet. In conclusion: a) there is a large non-specific RBC-carried compartment for estrone, estradiol, DHEA and testosterone deeply affected by sex; b) Prior exposure to a cafeteria (hyperlipidic) diet induced hormone distribution changes, affected by sex, which hint at sex-related structural differences in RBC membranes; c) We postulate that the RBC compartment may contribute to maintain free (i.e., fully active) sex hormone levels in a way similar to plasma proteins non-specific binding

Effect of Sex and Prior Exposure to a Cafeteria Diet on the Distribution of Sex Hormones between Plasma and Blood Cells

It is generally assumed that steroid hormones are carried in the blood free and/or bound to plasma proteins. We investigated whether blood cells were also able to bind/carry sex-related hormones: estrone, estradiol, DHEA and testosterone. Wistar male and female rats were fed a cafeteria diet for 30 days, which induced overweight. The rats were fed the standard rat diet for 15 additional days to minimize the immediate effects of excess ingested energy. Controls were always kept on standard diet. After the rats were killed, their blood was used for 1) measuring plasma hormone levels, 2) determining the binding of labeled hormones to washed red blood cells (RBC), 3) incubating whole blood with labeled hormones and determining the distribution of label between plasma and packed cells, discounting the trapped plasma volume, 4) determining free plasma hormone using labeled hormones, both through membrane ultrafiltration and dextran-charcoal removal. The results were computed individually for each rat. Cells retained up to 32% estrone, and down to 10% of testosterone, with marked differences due to sex and diet (the latter only for estrogens, not for DHEA and testosterone). Sex and diet also affected the concentrations of all hormones, with no significant diet effects for estradiol and DHEA, but with considerable interaction between both factors. Binding to RBC was non-specific for all hormones. Estrogen distribution in plasma compartments was affected by sex and diet. In conclusion: a) there is a large non-specific RBC-carried compartment for estrone, estradiol, DHEA and testosterone deeply affected by sex; b) Prior exposure to a cafeteria (hyperlipidic) diet induced hormone distribution changes, affected by sex, which hint at sex-related structural differences in RBC membranes; c) We postulate that the RBC compartment may contribute to maintain free (i.e., fully active) sex hormone levels in a way similar to plasma proteins non-specific binding

Explanatory pluralism in the medical sciences: theory and practice

Explanatory pluralism is the view that the best form and level of explanation depends on the kind of question one seeks to answer by the explanation, and that in order to answer all questions in the best way possible, we need more than one form and level of explanation. In the first part of this article, we argue that explanatory pluralism holds for the medical sciences, at least in theory. However, in the second part of the article we show that medical research and practice is actually not fully and truly explanatory pluralist yet. Although the literature demonstrates a slowly growing interest in non-reductive explanations in medicine, the dominant approach in medicine is still methodologically reductionist. This implies that non-reductive explanations often do not get the attention they deserve. We argue that the field of medicine could benefit greatly by reconsidering its reductive tendencies and becoming fully and truly explanatory pluralist. Nonetheless, trying to achieve the right balance in the search for and application of reductive and non-reductive explanations will in any case be a difficult exercise

Dual-specific chimeric antigen receptor T cells and an indirect vaccine eradicate a variety of large solid tumors in an immunocompetent, self-antigen setting

Purpose: While adoptive transfer of T cells bearing a chimeric antigen receptor (CAR) can eliminate substantial burdens of some leukemias, the ultimate challenge remains the eradication of large solid tumors for most cancers. We aimed to develop an immunotherapy approach effective against large tumors in an immunocompetent, self-antigen preclinical mouse model. Experimental Design: In this study, we generated dual-specific T cells expressing both a CAR specific for Her2 and a TCR specific for the melanocyte protein (gp100). We used a regimen of adoptive cell transfer incorporating vaccination (ACTIV), with recombinant vaccinia virus expressing gp100, to treat a range of tumors including orthotopic breast tumors and large liver tumors. Results: ACTIV therapy induced durable complete remission of a variety of Her2+ tumors, some in excess of 150 mm2, in immunocompetent mice expressing Her2 in normal tissues, including the breast and brain. Vaccinia virus induced extensive proliferation of T cells, leading to massive infiltration of T cells into tumors. Durable tumor responses required the chemokine receptor CXCR3 and exogenous IL-2, but were independent of IFN-gamma. Mice were resistant to tumor rechallenge, indicating immune memory involving epitope spreading. Evidence of limited neurologic toxicity was observed, associated with infiltration of cerebellum by T cells, but was only transient. Conclusions: This study supports a view that it is possible to design a highly effective combination immunotherapy for solid cancers, with acceptable transient toxicity, even when the target antigen is also expressed in vital tissuesThis work was supported by grants from the Cancer Council of Victoria, Australia (1066554), The Peter MacCallum Cancer Center Foundation, and the National Health and Medical Research Council (NHMRC) of Australia (1103352). C.Y. Slaney and P. Beavis were supported by Postdoctoral Fellowships from the National Breast Cancer Foundation of Australia. A.J. Davenport and S. Mardiana received Postgraduate Scholarships from the Fight Cancer Foundation and University of Melbourne respectively. R.W. Johnstone and M.J. Smyth were supported by Senior Principal Research Fellowships from the NHMRC. M.H. Kershaw and P.K. Darcy were supported by Senior Research Fellowships from the NHMRC. S. Ellis was supported by a New Investigator Grant from the NHMR

Do Humans Optimally Exploit Redundancy to Control Step Variability in Walking?

It is widely accepted that humans and animals minimize energetic cost while walking. While such principles predict average behavior, they do not explain the variability observed in walking. For robust performance, walking movements must adapt at each step, not just on average. Here, we propose an analytical framework that reconciles issues of optimality, redundancy, and stochasticity. For human treadmill walking, we defined a goal function to formulate a precise mathematical definition of one possible control strategy: maintain constant speed at each stride. We recorded stride times and stride lengths from healthy subjects walking at five speeds. The specified goal function yielded a decomposition of stride-to-stride variations into new gait variables explicitly related to achieving the hypothesized strategy. Subjects exhibited greatly decreased variability for goal-relevant gait fluctuations directly related to achieving this strategy, but far greater variability for goal-irrelevant fluctuations. More importantly, humans immediately corrected goal-relevant deviations at each successive stride, while allowing goal-irrelevant deviations to persist across multiple strides. To demonstrate that this was not the only strategy people could have used to successfully accomplish the task, we created three surrogate data sets. Each tested a specific alternative hypothesis that subjects used a different strategy that made no reference to the hypothesized goal function. Humans did not adopt any of these viable alternative strategies. Finally, we developed a sequence of stochastic control models of stride-to-stride variability for walking, based on the Minimum Intervention Principle. We demonstrate that healthy humans are not precisely “optimal,” but instead consistently slightly over-correct small deviations in walking speed at each stride. Our results reveal a new governing principle for regulating stride-to-stride fluctuations in human walking that acts independently of, but in parallel with, minimizing energetic cost. Thus, humans exploit task redundancies to achieve robust control while minimizing effort and allowing potentially beneficial motor variability

SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe

Aims: To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe. Methods and results: SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively. Conclusion: SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe