Are Today’s Medical School Graduates Performing the Same Number of Medical Procedures Compared to Graduates Ten Years Ago? A case for Simulation?

INTRODUCTION: Medical schools are charged with providing both a strong basic science and clinical curriculum for their students. In most institutions instruction in performing the core clinical procedures is part of the curriculum, but because of many constraints do medical students practice these procedures as many times as medical students in the past? Several studies have concluded that medical students today feel incompetent to perform basic clinical procedures at the time of graduation. [See PDF for complete abstract]

Detection of nonrandom association of alleles from the distribution of the number of heterozygous loci in a sample.

The distribution of the number of heterozygous loci in two randomly chosen gametes or in a random diploid zygote provides information regarding the nonrandom association of alleles among different genetic loci. Two alternative statistics may be employed for detection of nonrandom association of genes of different loci when observations are made on these distributions: observed variance of the number of heterozygous loci (s2k) and a goodness-of-fit criterion (X2) to contrast the observed distribution with that expected under the hypothesis of random association of genes. It is shown, by simulation, that s2k is statistically more efficient than X2 to detect a given extent of nonrandom association. Asymptotic normality of s2k is justified, and X2 is shown to follow a chi-square (chi 2) distribution with partial loss of degrees of freedom arising because of estimation of parameters from the marginal gene frequency data. Whenever direct evaluations of linkage disequilibrium values are possible, tests based on maximum likelihood estimators of linkage disequilibria require a smaller sample size (number of zygotes or gametes) to detect a given level of nonrandom association in comparison with that required if such tests are conducted on the basis of s2k. Summarization of multilocus genotype (or haplotype) data, into the different number of heterozygous loci classes, thus, amounts to appreciable loss of information.

Evaluating statistical methods used to estimate the number of postsynaptic receptors.

Calcium levels in spines play a significant role in determining the sign and magnitude of synaptic plasticity. The magnitude of calcium influx into spines is highly dependent on influx through N-methyl D-aspartate (NMDA) receptors, and therefore depends on the number of postsynaptic NMDA receptors in each spine. We have calculated previously how the number of postsynaptic NMDA receptors determines the mean and variance of calcium transients in the postsynaptic density, and how this alters the shape of plasticity curves. However, the number of postsynaptic NMDA receptors in the postsynaptic density is not well known. Anatomical methods for estimating the number of NMDA receptors produce estimates that are very different than those produced by physiological techniques. The physiological techniques are based on the statistics of synaptic transmission and it is difficult to experimentally estimate their precision. In this paper we use stochastic simulations in order to test the validity of a physiological estimation technique based on failure analysis. We find that the method is likely to underestimate the number of postsynaptic NMDA receptors, explain the source of the error, and re-derive a more precise estimation technique. We also show that the original failure analysis as well as our improved formulas are not robust to small estimation errors in key parameters.

Efficient estimation of the total number of acini in adult rat lung

Pulmonary airways are subdivided into conducting and gas-exchanging airways. An acinus is defined as the small tree of gas-exchanging airways, which is fed by the most distal purely conducting airway. Until now a dissector of five consecutive sections or airway casts were used to count acini. We developed a faster method to estimate the number of acini in young adult rats. Right middle lung lobes were critical point dried or paraffin embedded after heavy metal staining and imaged by X-ray micro-CT or synchrotron radiation-based X-rays tomographic microscopy. The entrances of the acini were counted in three-dimensional (3D) stacks of images by scrolling through them and using morphological criteria (airway wall thickness and appearance of alveoli). Segmentation stopper were placed at the acinar entrances for 3D visualizations of the conducting airways. We observed that acinar airways start at various generations and that one transitional bronchiole may serve more than one acinus. A mean of 5612 (±547) acini per lung and a mean airspace volume of 0.907 (±0.108) μL per acinus were estimated. In 60-day-old rats neither the number of acini nor the mean acinar volume did correlate with the body weight or the lung volume.

Estimating the Reproduction Number of Ebola Virus (EBOV) During the 2014 Outbreak in West Africa

The 2014 Ebola virus (EBOV) outbreak in West Africa is the largest outbreak of the genus Ebolavirus to date. To better understand the spread of infection in the affected countries, it is crucial to know the number of secondary cases generated by an infected index case in the absence and presence of control measures, i.e., the basic and effective reproduction number. In this study, I describe the EBOV epidemic using an SEIR (susceptible-exposed-infectious-recovered) model and fit the model to the most recent reported data of infected cases and deaths in Guinea, Sierra Leone and Liberia. The maximum likelihood estimates of the basic reproduction number are 1.51 (95% confidence interval [CI]: 1.50-1.52) for Guinea, 2.53 (95% CI: 2.41-2.67) for Sierra Leone and 1.59 (95% CI: 1.57-1.60) for Liberia. The model indicates that in Guinea and Sierra Leone the effective reproduction number might have dropped to around unity by the end of May and July 2014, respectively. In Liberia, however, the model estimates no decline in the effective reproduction number by end-August 2014. This suggests that control efforts in Liberia need to be improved substantially in order to stop the current outbreak.

Optimal number of oral implants for fixed reconstructions: a review of the literature.

BACKGROUND AND AIM So far there is little evidence from randomised clinical trials (RCT) or systematic reviews on the preferred or best number of implants to be used for the support of a fixed prosthesis in the edentulous maxilla or mandible, and no consensus has been reached. Therefore, we reviewed articles published in the past 30 years that reported on treatment outcomes for implant-supported fixed prostheses, including survival of implants and survival of prostheses after a minimum observation period of 1 year. MATERIAL AND METHODS MEDLINE and EMBASE were searched to identify eligible studies. Short and long-term clinical studies were included with prospective and retrospective study designs to see if relevant information could be obtained on the number of implants related to the prosthetic technique. Articles reporting on implant placement combined with advanced surgical techniques such as sinus floor elevation (SFE) or extensive grafting were excluded. Two reviewers extracted the data independently. RESULTS A primary search was broken down to 222 articles. Out of these, 29 studies comprising 26 datasets fulfilled the inclusion criteria. From all studies, the number of planned and placed implants was available. With two exceptions, no RCTs were found, and these two studies did not compare different numbers of implants per prosthesis. Eight studies were retrospective; all the others were prospective. Fourteen studies calculated cumulative survival rates for 5 and more years. From these data, the average survival rate was between 90% and 100%. The analysis of the selected articles revealed a clear tendency to plan 4 to 6 implants per prosthesis. For supporting a cross-arch fixed prosthesis in the maxilla, the variation is slightly greater. CONCLUSIONS In spite of a dispersion of results, similar outcomes are reported with regard to survival and number of implants per jaw. Since the 1990s, it was proven that there is no need to install as many implants as possible in the available jawbone. The overwhelming majority of articles dealing with standard surgical procedures to rehabilitate edentulous jaws uses 4 to 6 implants.

Increased number of non-degranulated mast cells in pancreatic ductal adenocarcinoma but not in acute pancreatitis.

Increasing evidence indicates that tumor microenvironment (TME) is crucial in tumor survival and metastases. Inflammatory cells accumulate around tumors and strangely appear to be permissive to their growth. One key stroma cell is the mast cell (MC), which can secrete numerous pro- and antitumor molecules. We investigated the presence and degranulation state of MC in pancreatic ductal adenocarcinoma (PDAC) as compared to acute ancreatitis (AP). Three different detection methods: (a) toluidine blue staining, as well as immunohistochemistry for (b) tryptase and (c) c-kit, were utilized to assess the number and extent of degranulation of MC in PDAC tissue (n=7), uninvolved pancreatic tissue derived from tumor-free margins (n=7) and tissue form AP (n=4). The number of MC detected with all three methods was significantly increased in PDAC, as compared to normal pancreatic tissue derived from tumor-free margins (p<0.05). The highest number of MC was identified by c-kit, 22.2∓7.5 per high power field (HPF) in PDAC vs 9.7∓5.1 per HPF in normal tissue. Contrary to MC in AP, where most of the detected MC were found degranulated, MC in PDAC appeared intact. In conclusion, MC are increased in number, but not degranulated in PDAC, suggesting that they may contribute to cancer growth by permitting selective release of pro-tumorogenic molecules.

More volunteers in football clubs. An evaluation of a method to increase the number of volunteers

An increasing number of clubs experience difficulties in recruiting and retaining sufficient numbers of volunteers to manage and staff their clubs (Lamprecht, Fischer, & Stamm, 2012). In order to facilitate volunteer recruitment, sport clubs need a specific strategy to recruit and retain volunteers for both formal positions and ad hoc tasks. Therefore, the intervention “More Volunteers in Football Clubs” was designed and its impact was evaluated in detail. The question this evaluation research wants to address is: Can football clubs recruit and retain volunteers successfully by implementing the intervention “More Volunteers in Football Clubs”? The designed intervention is based on the different expectations and needs of volunteers, as well as non-profit human resource management and organisational development management, with a strong emphasis on club-specific counseling and support. Task forces of the twelve participating football clubs attended four workshops in which they received tailor made counseling to reach the desired number of volunteers. The intervention has been implemented and its effectiveness tested in cooperation with the Swiss Football Federation with twelve Swiss football clubs following a pretest, intervention, posttest design Data have been gathered and analysed using a combination of qualitative and quantitative methods. Outcome measurements are: volunteer rate, number of recruited volunteers, number of filled volunteer positions and volunteer satisfaction. Four months after the intervention all clubs that completed the proposed intervention were successful in recruiting the desired number of volunteers. Further, all participating clubs found the intervention helpful and would recommend other clubs to participate as well. With the development of this practical intervention a solution for football clubs is provided to overcome the difficulties in recruiting and retaining sufficient numbers of volunteers. Lamprecht, M., Fischer, A., & Stamm, H.-P. (2012). Sportvereine in der Schweiz. Strukturen, Leistungen, Herausforderungen. Zürich, Switzerland: Seismo.

Competitive fitness in coronaviruses is not correlated with size or number of double-membrane vesicles under reduced-temperature growth conditions.

Positive-stranded viruses synthesize their RNA in membrane-bound organelles, but it is not clear how this benefits the virus or the host. For coronaviruses, these organelles take the form of double-membrane vesicles (DMVs) interconnected by a convoluted membrane network. We used electron microscopy to identify murine coronaviruses with mutations in nsp3 and nsp14 that replicated normally while producing only half the normal amount of DMVs under low-temperature growth conditions. Viruses with mutations in nsp5 and nsp16 produced small DMVs but also replicated normally. Quantitative reverse transcriptase PCR (RT-PCR) confirmed that the most strongly affected of these, the nsp3 mutant, produced more viral RNA than wild-type virus. Competitive growth assays were carried out in both continuous and primary cells to better understand the contribution of DMVs to viral fitness. Surprisingly, several viruses that produced fewer or smaller DMVs showed a higher fitness than wild-type virus at the reduced temperature, suggesting that larger and more numerous DMVs do not necessarily confer a competitive advantage in primary or continuous cell culture. For the first time, this directly demonstrates that replication and organelle formation may be, at least in part, studied separately during infection with positive-stranded RNA virus. IMPORTANCE The viruses that cause severe acute respiratory syndrome (SARS), poliomyelitis, and hepatitis C all replicate in double-membrane vesicles (DMVs). The big question about DMVs is why they exist in the first place. In this study, we looked at thousands of infected cells and identified two coronavirus mutants that made half as many organelles as normal and two others that made typical numbers but smaller organelles. Despite differences in DMV size and number, all four mutants replicated as efficiently as wild-type virus. To better understand the relative importance of replicative organelles, we carried out competitive fitness experiments. None of these viruses was found to be significantly less fit than wild-type, and two were actually fitter in tests in two kinds of cells. This suggests that viruses have evolved to have tremendous plasticity in the ability to form membrane-associated replication complexes and that large and numerous DMVs are not exclusively associated with efficient coronavirus replication.

Pattern and process: competition causes regular spacing of individuals within plant populations

1 We used simulated and experimental plant populations to analyse mortality-driven pattern formation under size-dependent competition. Larger plants had an advantage under size-asymmetric but not under symmetric competition. Initial patterns were random or clumped. 2 The simulations were individual-based and spatially explicit. Size-dependent competition was modelled with different rules to partition overlapping zones of influence. 3 The experiment used genotypes of Arabidopsis thaliana with different morphological plasticity and hence size-dependent competition. Compared with wild types, transgenic individuals over-expressed phytochrome A and had decreased plasticity because of disabled phytochrome-mediated shade avoidance. Therefore, competition among transgenics was more asymmetric compared with wild-types. 4 Density-dependent mortality under symmetric competition did not substantially change the initial spatial pattern. Conversely, simulations under asymmetric competition and experimental patterns of transgenic over-expressors showed patterns of survivors that deviated substantially from random mortality independent of initial patterns. 5 Small-scale initial patterns of wild types were regular rather than random or clumped. We hypothesize that this small-scale regularity may be explained by early shade avoidance of seedlings in their cotyledon stage. 6 Our experimental results support predictions from an individual-based simulation model and support the conclusion that regular spatial patterns of surviving individuals should be interpreted as evidence for strong, asymmetric competitive interactions and subsequent density-dependent mortality.

Trajectories of psychological adaptation to marital breakup after a long-term marriage

Background: Marital dissolution is known to be among the most stressful life events with long- reaching negative consequences on individuals’ lives. A limitation in research to date is that most studies have focused on the impact of marital disruption on well-being outcomes in younger adults. Furthermore, although population-based studies on divorce document a broad range of negative effects, more fine-grained analyses reveal a large heterogeneity in people’s adjustment, which is still not well understood. Objective: To explore trajectories of psychological adaptation to marital breakup after a long-term marriage, and to examine variables accounting for recovery or chronicity in terms of intrapersonal resources (personality, trait resilience, personal growth), relationship variables (satisfaction with ex- relationship, length of marriage, time since divorce) and socio-demographic variables (age, gender, financial situation). Methods: Latent transition analysis is used to examine the course of psychological adaptation (i.e., depressive symptoms, life satisfaction, hopelessness, mourning and subjective health) to divorce over two years among five profiles of 308 divorcees (mean age: 55.6 years; average duration of former marriage: 23.62 years): Two larger groups of individuals, the one which adapted very well (‘resilients’, 29%), the other quite well (‘average copers’, 49%), and three groups with major difficulties (‘vulnerables’, 6%; ‘malcontents’, 12%; and ‘resigned’, 4%). In a second step the differences among transition patterns were explored on the basis of the distal variables (i.e., intrapersonal resources, relationship variables, socio-demographics). Results: Although the probability of upward changes was higher for those individuals with lower adaptation at time 1, only a small number of individuals made an upward change from the maladapted to the well-adapted groups throughout the two years. The groups of copers and resilients remained stable in their psychological adaption. The most consistent results related to upward changes were intrapersonal resources, namely the NEO personality traits and trait resilience. Conclusion: The majority of individuals divorcing after a long-term marriage adapt successfully over time. Adaptation trajectories depend primarily on intrapersonal resources. However, a minority of divorcees exhibit enduring difficulties. Knowledge about the diversity of these trajectories of vulnerability could be of great help for designing psychological interventions to better tackle this critical life event.

Esthetic, Functional, and Everyday Life Assessment of Individuals with Cleft Lip and/or Palate

OBJECTIVES To evaluate the level of satisfaction of individuals with cleft lip and/or palate (CLP) and their parents concerning the esthetic and functional treatment outcomes, the impact of the cleft on everyday life, and potential associations with treatment outcome satisfaction. SUBJECTS AND METHODS The sample consisted of 33 patients (7 CP, 20 unilateral CLP, and 6 bilateral CLP; median age: 17.1, range: 9.0-33.1 years) and 30 parents, who responded to a questionnaire in an interview-guided session. All participants received their orthodontic treatment at the Department of Orthodontics in the University of Athens. RESULTS Patients and their parents were quite satisfied with esthetics and function. Patients with UCLP primarily were concerned about nose esthetics (BCLP about lip esthetics and CP about speech). Increased satisfaction was associated with decreased influence of the cleft in everyday life (0.35 < rho < 0.64, P < 0.05). Parents reported significant influence of the cleft on family life, while patients did not. CONCLUSIONS Despite the limited sample size of subgroups, the main concerns of patients with different cleft types and the importance of satisfying lip, nose, and speech outcomes for an undisturbed everyday life were quite evident. Thus, the need for targeted treatment strategies is highlighted for individuals with cleft lip and/or palate.

Increased spread and replication efficiency of Listeria monocytogenes in organotypic brain-slices is related to multilocus variable number of tandem repeat analysis (MLVA) complex.

BACKGROUND Listeria (L.) monocytogenes causes fatal infections in many species including ruminants and humans. In ruminants, rhombencephalitis is the most prevalent form of listeriosis. Using multilocus variable number tandem repeat analysis (MLVA) we recently showed that L. monocytogenes isolates from ruminant rhombencephalitis cases are distributed over three genetic complexes (designated A, B and C). However, the majority of rhombencephalitis strains and virtually all those isolated from cattle cluster in MLVA complex A, indicating that strains of this complex may have increased neurotropism and neurovirulence. The aim of this study was to investigate whether ruminant rhombencephalitis strains have an increased ability to propagate in the bovine hippocampal brain-slice model and can be discriminated from strains of other sources. For this study, forty-seven strains were selected and assayed on brain-slice cultures, a bovine macrophage cell line (BoMac) and a human colorectal adenocarcinoma cell line (Caco-2). They were isolated from ruminant rhombencephalitis cases (n = 21) and other sources including the environment, food, human neurolisteriosis cases and ruminant/human non-encephalitic infection cases (n = 26). RESULTS All but one L. monocytogenes strain replicated in brain slices, irrespectively of the source of the isolate or MLVA complex. The replication of strains from MLVA complex A was increased in hippocampal brain-slice cultures compared to complex C. Immunofluorescence revealed that microglia are the main target cells for L. monocytogenes and that strains from MLVA complex A caused larger infection foci than strains from MLVA complex C. Additionally, they caused larger plaques in BoMac cells, but not CaCo-2 cells. CONCLUSIONS Our brain slice model data shows that all L. monocytogenes strains should be considered potentially neurovirulent. Secondly, encephalitis strains cannot be conclusively discriminated from non-encephalitis strains with the bovine organotypic brain slice model. The data indicates that MLVA complex A strains are particularly adept at establishing encephalitis possibly by virtue of their higher resistance to antibacterial defense mechanisms in microglia cells, the main target of L. monocytogenes.