A model for selection of eyespots on butterfly wings

The development of eyespots on the wing surface of butterflies of the family Nympalidae is one of the most studied examples of biological pattern formation.However, little is known about the mechanism that determines the number and precise locations of eyespots on the wing. Eyespots develop around signaling centers, called foci, that are located equidistant from wing veins along the midline of a wing cell (an area bounded by veins). A fundamental question that remains unsolved is, why a certain wing cell develops an eyespot, while other wing cells do not. We illustrate that the key to understanding focus point selection may be in the venation system of the wing disc. Our main hypothesis is that changes in morphogen concentration along the proximal boundary veins of wing cells govern focus point selection. Based on previous studies, we focus on a spatially two-dimensional reaction-diffusion system model posed in the interior of each wing cell that describes the formation of focus points. Using finite element based numerical simulations, we demonstrate that variation in the proximal boundary condition is sufficient to robustly select whether an eyespot focus point forms in otherwise identical wing cells. We also illustrate that this behavior is robust to small perturbations in the parameters and geometry and moderate levels of noise. Hence, we suggest that an anterior-posterior pattern of morphogen concentration along the proximal vein may be the main determinant of the distribution of focus points on the wing surface. In order to complete our model, we propose a two stage reaction-diffusion system model, in which an one-dimensional surface reaction-diffusion system, posed on the proximal vein, generates the morphogen concentrations that act as non-homogeneous Dirichlet (i.e., fixed) boundary conditions for the two-dimensional reaction-diffusion model posed in the wing cells. The two-stage model appears capable of generating focus point distributions observed in nature. We therefore conclude that changes in the proximal boundary conditions are sufficient to explain the empirically observed distribution of eyespot focus points on the entire wing surface. The model predicts, subject to experimental verification, that the source strength of the activator at the proximal boundary should be lower in wing cells in which focus points form than in those that lack focus points. The model suggests that the number and locations of eyespot foci on the wing disc could be largely controlled by two kinds of gradients along two different directions, that is, the first one is the gradient in spatially varying parameters such as the reaction rate along the anterior-posterior direction on the proximal boundary of the wing cells, and the second one is the gradient in source values of the activator along the veins in the proximal-distal direction of the wing cell

Tracking Performance of the Scintillating Fiber Detector in the K2K Experiment

The K2K long-baseline neutrino oscillation experiment uses a Scintillating Fiber Detector (SciFi) to reconstruct charged particles produced in neutrino interactions in the near detector. We describe the track reconstruction algorithm and the performance of the SciFi after three years of operation.Comment: 24pages,18 figures, and 1 table. Preprint submitted to NI

Factors considered by medical students when formulating their specialty preferences in Japan: findings from a qualitative study

<p>Abstract</p> <p>Background</p> <p>Little research addresses how medical students develop their choice of specialty training in Japan. The purpose of this research was to elucidate factors considered by Japanese medical students when formulating their specialty choice.</p> <p>Methods</p> <p>We conducted qualitative interviews with 25 Japanese medical students regarding factors influencing specialty preference and their views on roles of primary versus specialty care. We qualitatively analyzed the data to identify factors students consider when developing specialty preferences, to understand their views about primary and subspecialty care, and to construct models depicting the pathways to specialization.</p> <p>Results</p> <p>Students mention factors such as illness in self or close others, respect for family member in the profession, preclinical experiences in the curriculum such as labs and dissection, and aspects of patient care such as the clinical atmosphere, charismatic role models, and doctor-patient communication as influential on their specialty preferences. Participating students could generally distinguish between subspecialty care and primary care, but not primary care and family medicine. Our analysis yields a "Two Career" model depicting how medical graduates can first train for hospital-based specialty practice, and then switch to mixed primary/specialty care outpatient practice years later without any requirement for systematic training in principles of primary care practice.</p> <p>Conclusion</p> <p>Preclinical and clinical experiences as well as role models are reported by Japanese students as influential factors when formulating their specialty preferences. Student understanding of family medicine as a discipline is low in Japan. Students with ultimate aspirations to practice outpatient primary care medicine do not need to commit to systematic primary care training after graduation. The Two Career model of specialization leaves the door open for medical graduates to enter primary care practice at anytime regardless of post-graduate residency training choice.</p

Prognostic value of simple frailty and malnutrition screening tools in patients with acute heart failure due to left ventricular systolic dysfunction

Background: Frailty and malnutrition are common in patients with heart failure (HF), and are associated with adverse outcomes. We studied the prognostic value of three malnutrition and three frailty indices in patients admitted acutely to hospital with HF. Methods: 265 consecutive patients [62% males, median age 80 (interquartile range (IQR): 72–86) years, median NTproBNP 3633 (IQR: 2025–6407) ng/l] admitted with HF between 2013 and 2014 were enrolled. Patients were screened for frailty using the Derby frailty index (DFI), acute frailty network (AFN) frailty criteria, and clinical frailty scale (CFS) and for malnutrition using the geriatric nutritional risk index (GNRI), controlling nutritional status (CONUT) score and prognostic nutritional index (PNI). Results: According to the CFS (> 4), DFI, and AFN, 53, 50, and 53% were frail, respectively. According to the GNRI (≤ 98), CONUT score (> 4), and PNI (≤ 38), 46, 46, and 42% patients were malnourished, respectively. During a median follow-up of 598 days (IQR 319–807 days), 113 patients died. One year mortality was 1% for those who were neither frail nor malnourished; 15% for those who were either malnourished or frail; and 65% for those who were both malnourished and frail. Amongst the malnutrition scores, PNI, and amongst the frailty scores, CFS increased model performance most compared with base model. A final model, including CFS and PNI, increased c-statistic for mortality prediction from 0.68 to 0.84. Conclusion: Worsening frailty and malnutrition indices are strongly related to worse outcome in patients hospitalised with HF

Hypertensive patients' perceptions of their physicians' knowledge about them: a cross-sectional study in Japan

<p>Abstract</p> <p>Background</p> <p>In order to evaluate the difference in quality of primary care provided by physicians between the types of medical institutions in Japan, we examined whether the physicians' comprehensive knowledge of their patients is perceived differently by the patients seen at clinics and hospitals.</p> <p>Methods</p> <p>Patients with prescriptions for hypertensive drugs were approached sequentially at 13 pharmacies, and were administered a questionnaire on their perception of their physician's knowledge about them. Data were obtained for 687 patients (362 from clinics and 325 from hospitals). A physician's knowledge of his or her patients was assessed according to six aspects: their medical history, their current medications, history of allergy, what worries patients most about their health, patients' values and beliefs on their health, and patients' roles and responsibilities at work, home, or school. Responses were scored from 1 through 6 (1: knows very well; 6: doesn't know at all).</p> <p>Results</p> <p>Patients treated in clinics were seen more frequently, for a longer period, and had fewer complications than the patients who were treated in hospitals. Among the six aspects of physicians' knowledge assessed, 79.3% of the patients reported that their physicians knew their complete list of medications "very well or well," while 28.3% reported the same about their roles and responsibilities at work, home, or school. Physicians in clinics were considered to know their patients' worries about their health (p = 0.004) and the roles and responsibilities of the patients at work, home, or school (p = 0.028) well. Multiple regression analysis showed that the type of medical institutions remained as a significant variable only for the aspect of patients' worries about their health. The factor that consistently affected the patients' perception of physicians' knowledge about them was the patients' age.</p> <p>Conclusions</p> <p>Hypertensive patients' perceptions of their physicians' knowledge about them did not differ significantly between clinics and hospitals in Japan for most of the aspects. In order to differentiate the roles of physicians in hospitals and clinics better and ensure the quality of primary care, the establishment of a standardized educational system to train primary care physicians better is recommended.</p

Undergraduate educational environment, perceived preparedness for postgraduate clinical training, and pass rate on the National Medical Licensure Examination in Japan

<p>Abstract</p> <p>Background</p> <p>We investigated the views of newly graduating physicians on their preparedness for postgraduate clinical training, and evaluated the relationship of preparedness with the educational environment and the pass rate on the National Medical Licensure Examination (NMLE).</p> <p>Methods</p> <p>Data were obtained from 2429 PGY-1 physicians-in-training (response rate, 36%) using a mailed cross-sectional survey. The Dundee Ready Education Environment Measure (DREEM) inventory was used to assess the learning environment at 80 Japanese medical schools. Preparedness was assessed based on 6 clinical areas related to the Association of American Medical Colleges Graduation Questionnaire.</p> <p>Results</p> <p>Only 17% of the physicians-in-training felt prepared in the area of general clinical skills, 29% in basic knowledge of diagnosis and management of common conditions, 48% in communication skills, 19% in skills associated with evidence-based medicine, 54% in professionalism, and 37% in basic skills required for a physical examination. There were substantial differences among the medical schools in the perceived preparedness of their graduates. Significant positive correlations were found between preparedness for all clinical areas and a better educational environment (all p < 0.01), but there were no significant associations between the pass rate on the NMLE and perceived preparedness for any clinical area, as well as pass rate and educational environment (all p > 0.05).</p> <p>Conclusion</p> <p>Different educational environments among universities may be partly responsible for the differences in perceived preparedness of medical students for postgraduate clinical training. This study also highlights the poor correlation between self-assessed preparedness for practice and the NMLE.</p

Ingestion of radioactively contaminated diets for two generations in the pale grass blue butterfly

Background: The release of radioactive materials due to the Fukushima nuclear accident has raised concern regarding the biological impacts of ingesting radioactively contaminated diets on organisms. We previously performed an internal exposure experiment in which contaminated leaves collected from polluted areas were fed to larvae of the pale grass blue butterfly, Zizeeria maha, from Okinawa, which is one of the least polluted localities in Japan. Using the same experimental system, in the present study, we further examined the effects of low-level-contaminated diets on this butterfly. Leaves were collected from two localities in Tohoku (Motomiya (161 Bq/kg) and Koriyama (117 Bq/kg)); two in Kanto (Kashiwa (47.6 Bq/kg) and Musashino (6.4 Bq/kg)); one in Tokai (Atami (2.5 Bq/kg)); and from Okinawa (0.2 Bq/kg). In addition to the effects on the first generation, we examined the possible transgenerational effects of the diets on the next generation.Results: In the first generation, the Tohoku groups showed higher rates of mortality and abnormalities and a smaller forewing size than the Okinawa group. The mortality rates were largely dependent on the ingested dose of caesium. The survival rates of the Kanto-Tokai groups were greater than 80%, but the rates in the Tohoku groups were much lower. In the next generation, the survival rates in the Tohoku groups were below 20%, whereas those of the Okinawa groups were above 70%. The survival rates in the second generation were independent of the locality of the leaves ingested by the first generation, indicating that the diet in the second generation was the determinant of their survival. Moreover, a smaller forewing size was observed in the Tohoku groups in the second generation. However, the forewing size was inversely correlated with the cumulative caesium dose ingested throughout the first and second generations, indicating that the diet in the first generation also influenced the forewing size of the second generation.Conclusions: Biological effects are detectable under a low ingested dose of radioactivity from a contaminated diet. The effects are transgenerational but can be overcome by ingesting a non-contaminated diet, suggesting that at least some of the observed effects are attributable to non-genetic physiological changes

Dysregulated Nephrin in Diabetic Nephropathy of Type 2 Diabetes: A Cross Sectional Study

Podocyte specific proteins are dysregulated in diabetic nephropathy, though the extent of their expression loss is not identical and may be subject to different regulatory factors. Quantifying the degree of loss may help identify the most useful protein to use as an early biomarker of diabetic nephropathy.Protein expression of synaptopodin, podocin and nephrin were quantified in 15 Type 2 diabetic renal biopsies and 12 control patients. We found statistically significant downregulation of synaptopodin (P<0.0001), podocin (P = 0.0002), and nephrin (P<0.0001) in kidney biopsies of diabetic nephropathy as compared with controls. Urinary nephrin levels (nephrinuria) were then measured in 66 patients with Type 2 diabetes and 10 healthy controls by an enzyme-linked immunosorbent assay (Exocell, Philadelphia, PA). When divided into groups according to normo-, micro-, and macroalbuminuria, nephrinuria was found to be present in 100% of diabetic patients with micro- and macroalbuminuria, as well as 54% of patients with normoalbuminuria. Nephrinuria also correlated significantly with albuminuria (rho = 0.89, p<0.001), systolic blood pressure (rho = 0.32, p = 0.007), and correlated negatively with serum albumin (rho = -0.48, p<0.0001) and eGFR (rho = -0.33, p = 0.005).These data suggest that key podocyte-specific protein expressions are significantly and differentially downregulated in diabetic nephropathy. The finding that nephrinuria is observed in a majority of these normoalbuminuric patients demonstrates that it may precede microalbuminuria. If further research confirms nephrinuria to be a biomarker of pre-clinical diabetic nephropathy, it would shed light on podocyte metabolism in disease, and raise the possibility of new and earlier therapeutic targets

Measurement of neutrino oscillation by the K2K experiment

We present measurements of nu(mu) disappearance in K2K, the KEK to Kamioka long-baseline neutrino oscillation experiment. One-hundred and twelve beam-originated neutrino events are observed in the fiducial volume of Super-Kamiokande with an expectation of 158.1(-8.6)(+9.2) events without oscillation. A distortion of the energy spectrum is also seen in 58 single-ring muonlike events with reconstructed energies. The probability that the observations are explained by the expectation for no neutrino oscillation is 0.0015% (4.3 sigma). In a two-flavor oscillation scenario, the allowed Delta m(2) region at sin(2)2 theta=1 is between 1.9 and 3.5x10(-3) eV(2) at the 90% C.L. with a best-fit value of 2.8x10(-3) eV(2)