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Tan spot, caused by the necrotrophic fungal pathogen Pyrenophora tritici-repentis (Ptr), is an important disease of durum and common wheat worldwide. Compared to common wheat, less is known about the genetics and molecular basis of tan spot resistance in durum wheat. We evaluated 510 durum lines from the Global Durum wheat Panel (GDP) for sensitivity to the necrotrophic effectors (NEs) Ptr ToxA and Ptr ToxB, and for reaction to Ptr isolates representing races 1–5. Overall, susceptible durum lines were most prevalent in South Asia, the Middle East, and North Africa. Genome-wide association analysis showed the resistance locus Tsr7 was significantly associated with tan spot caused by races 2 and 3, but not races 1, 4, or 5. The NE sensitivity genes Tsc1 and Tsc2 were associated with susceptibility to Ptr ToxC- and Ptr ToxB-producing isolates, respectively, but Tsn1 was not associated with tan spot caused by Ptr ToxA-producing isolates, which further validates that the Tsn1-Ptr ToxA interaction does not play a significant role in tan spot development in durum. A unique locus on chromosome arm 2AS was associated with tan spot caused by race 4, a race once considered avirulent. A novel trait characterized by expanding chlorosis leading to increased disease severity caused by the Ptr ToxB-producing race 5 isolate DW5 was identified, and this trait was governed by a locus on chromosome 5B. We recommend that durum breeders select resistance alleles at the Tsr7, Tsc1, Tsc2, and the chromosome 2AS loci to obtain broad resistance to tan spot.

BACKGROUND Providing permanent supportive housing to chronically homeless persons living with human immunodeficiency virus (PLH) contributes to improved human immunodeficiency virus (HIV) outcomes, including adherence to antiretroviral therapy (ART). This study seeks to understand whether certain components of housing, namely intensity of case management and specialized HIV housing programs, affects ART adherence for PLH in supportive housing. METHODS From 2015 to 2019 we conducted quantitative assessments with 157 PLH in supportive housing at baseline, 6-, 12-, and 18-month postbaseline to identify factors associated with ART adherence. General Estimating Equations for repeated measures were performed to assess bivariate and multivariate measures. RESULTS Two thirds of PLH in supportive housing reported 95% or greater adherence to ART. Multivariate analyses indicate that neither intensity of case management services nor specialized housing for PLH were associated with greater ART adherence. Greater time since diagnosis was positively associated with ART adherence. Greater depressive symptoms and African American race were negatively associated with ART adherence. CONCLUSIONS Study findings reveal that although prior research has established the importance of receipt of housing for homeless PLH, the type or intensity of case management services associated with that housing may not be as important as simply being housed. Our results highlight the importance of considering mental health and more recent HIV diagnosis when developing treatment and case management plans to enhance residents' ART adherence.

Despite the availability of contraceptives, cultural practices and social factors create barriers that prevent women in Ghana from realizing their reproductive health potential. The purpose of the field study was to examine individual and community level factors related to contraceptive access, family planning, and reproductive health challenges among women in Kumasi, Ghana. Specifically, we conducted a field-based comparison of women’s health-related issues in Kumasi and the US to determine areas of similarities and differences. Since our focus was Kumasi in general and the Suntreso Government Hospital in particular, we used convenience sampling. Thus, study results are not generalizable to the entire population of Ghana. Given the short duration of the entire field study (three weeks), and the fact that information on the women’s health areas of focus in Ghana is available in the US, secondary data from various sources were used for the US comparison. Utilizing a cross-sectional, mixed-methods study design, 100 women of reproductive age were surveyed. Results showed that 69.0% of study participants in Kumasi knew where to go to access birth control services but had little desire to use them. Like the study participants in Kumasi, most women in the US also know where to access reproductive health services but are more desirous and interested in using such services. We also found that while cultural norms and gender roles served as primary barriers to family planning and contraceptive access for women in Kumasi, access to health insurance is the barrier in the US. Copyright © 2022 Gibson et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0.

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Background Diagnostic intuition is a rapid, non-analytic, unconscious mode of reasoning. A small body of evidence points to the ubiquity of intuition, and its usefulness in generating diagnostic hypotheses and ascertaining severity of illness. Little is known about how experienced physicians understand this phenomenon, and how they work with it in clinical practice. Methods Descriptions of how experienced physicians perceive their use of diagnostic intuition in clinical practice were elicited through interviews conducted with 30 physicians in emergency, internal and family medicine. Each participant was asked to share stories of diagnostic intuition, including times when intuition was both correct and incorrect. Multiple coders conducted descriptive analysis to analyze the salient aspects of these stories. Results Physicians provided descriptions of what diagnostic intuition is, when it occurs and what type of activity it prompts. From stories of correct intuition, a typology of four different types of intuition was identified: Sick/Not Sick, Something Not Right, Frame-shifting and Abduction. Most physician accounts of diagnostic intuition linked this phenomenon to non-analytic reasoning and emphasized the importance of experience in developing a trustworthy sense of intuition that can be used to effectively engage analytic reasoning to evaluate clinical evidence. Conclusions The participants recounted myriad stories of diagnostic intuition that alerted them to unusual diagnoses, previous diagnostic error or deleterious trajectories. While this qualitative study can offer no conclusions about the representativeness of these stories, it suggests that physicians perceive clinical intuition as beneficial for correcting and advancing diagnoses of both common and rare conditions.

Background Prior studies indicate that the auditory mismatch response is sensitive to early alterations in brain development in multiple developmental disorders. Prenatal alcohol exposure is known to impact early auditory processing. The current study hypothesized alterations in the mismatch response in young children with fetal alcohol spectrum disorders (FASD). Methods Participants in this study were 9 children with a FASD and 17 control children (Control) aged 3 to 6 years. Participants underwent magnetoencephalography and structural magnetic resonance imaging scans separately. We compared groups on neurophysiological mismatch negativity (MMN) responses to auditory stimuli measured using the auditory oddball paradigm. Frequent (1,000 Hz) and rare (1,200 Hz) tones were presented at 72 dB. Results There was no significant group difference in MMN response latency or amplitude represented by the peak located ~200 ms after stimulus presentation in the difference time course between frequent and infrequent tones. Examining the time courses to the frequent and infrequent tones separately, repeated measures analysis of variance with condition (frequent vs. rare), peak (N100m and N200m), and hemisphere as within-subject factors and diagnosis and sex as the between-subject factors showed a significant interaction of peak by diagnosis (p = 0.001), with a pattern of decreased amplitude from N100m to N200m in Control children and the opposite pattern in children with FASD. However, no significant difference was found with the simple effects comparisons. No group differences were found in the response latencies of the rare auditory evoked fields. Conclusions The results indicate that there was no detectable effect of alcohol exposure on the amplitude or latency of the MMNm response to simple tones modulated by frequency change in preschool-aged children with FASD. However, while discrimination abilities to simple tones may be intact, early auditory sensory processing revealed by the interaction between N100m and N200m amplitude indicates that auditory sensory processing may be altered in children with FASD.

The cortical responses to auditory stimuli undergo rapid and dramatic changes during the first 3 years of life in normally developing (ND) children, with decreases in latency and changes in amplitude in the primary peaks. However, most previous studies have focused on children >3 years of age. The analysis of data from the early stages of development is challenging because the temporal pattern of the evoked responses changes with age (e.g., additional peaks emerge with increasing age) and peak latency decreases with age. This study used the topography of the auditory evoked magnetic field (AEF) to identify the auditory components in ND children between 6 and 68 months (n = 48). The latencies of the peaks in the AEF produced by a tone burst (ISI 2 ± 0.2 s) during sleep decreased with age, consistent with previous reports in awake children. The peak latencies of the AEFs in ND children and children with autism spectrum disorder (ASD) were compared. Previous studies indicate that the latencies of the initial components of the auditory evoked potential (AEP) and the AEF are delayed in children with ASD when compared to age-matched ND children >4 years of age. We speculated whether the AEF latencies decrease with age in children diagnosed with ASD as in ND children, but with uniformly longer latencies before the age of about 4 years. Contrary to this hypothesis, the peak latencies did not decrease with age in the ASD group (24-62 months, n = 16) during sleep (unlike in the age-matched controls), although the mean latencies were longer in the ASD group as in previous studies. These results are consistent with previous studies indicating delays in auditory latencies, and they indicate a different maturational pattern in ASD children and ND children. Longitudinal studies are needed to confirm whether the AEF latencies diverge with age, starting at around 3 years, in these 2 groups of children.

According to the dual process model of reasoning, physicians make diagnostic decisions using two mental systems: System 1, which is rapid, unconscious, and intuitive, and System 2, which is slow, rational, and analytical. Currently, little is known about physicians’ use of System 1 or intuitive reasoning in practice. In a qualitative study of clinical reasoning, physicians were asked to tell stories about times when they used intuitive reasoning while working up an acutely unwell patient, and we combine socio-narratology and rhetorical theory to analyze physicians’ stories. Our analysis reveals that in describing their work, physicians draw on two competing narrative structures: one that is aligned with an evidence-based medicine approach valuing System 2 and one that is aligned with cooperative decision making involving others in the clinical environment valuing System 1. Our findings support an understanding of clinical reasoning as distributed, contextual, and influenced by professional culture.

OBJECTIVES: Follow‐up colonoscopy rates among persons with positive fecal occult blood test results (FOBT + ) remain suboptimal in many jurisdictions. In Ontario, Canada, primary care providers (PCPs) are responsible for arranging follow‐up colonoscopies. The objectives were to understand the reasons for a lack of follow‐up colonoscopy and any action plans to address follow‐up. METHODS: Semi‐structured interviews were conducted with 30 FOBT+ persons and 30 PCPs in Ontario. Eligible FOBT+ persons were identified through administrative databases and included those aged 50‐74, with a 6‐12 month old FOBT+, no follow‐up colonoscopy, and no prior colorectal cancer diagnosis or colectomy. Eligible PCPs had ≥1 rostered FOBT+ person without follow‐up colonoscopy. Transcripts were analyzed inductively using Nvivo 11 (QSR International Pty Ltd., 2015). RESULTS: Reasons for lack of follow‐up colonoscopy were: person and/or provider believed the FOBT + was a false positive; person was afraid of colonoscopy; person had other health issues; and breakdown in communication of FOBT+ results or colonoscopy appointments. PCPs who initially recommended follow‐up colonoscopy did not change the minds of the persons who dismissed the FOBT+ as a false positive and/or who were afraid of the procedure. These FOBT+ persons negotiated an alternative follow‐up action plan including repeating the FOBT or not following‐up. CONCLUSIONS: PCPs may not adequately counsel FOBT+ persons who believe the FOBT+ is a false positive and/or fear colonoscopy. PCPs may lack fail‐safe systems to communicate FOBT+ results and colonoscopy appointments. Using navigators may help address these barriers and increase follow‐up rates.

We analyzed survey data from a nationally representative study of Canadian labor force participants (n = 5,667) to examine the social distribution and mental health of those who provide unpaid health-related care to a family member or relative. As part of these analyses, we investigated gender differences in the association between caregiving frequency and mental health. Multivariate analyses revealed evidence that women caregivers experienced greater health penalties than men with care commitments. Mediation analyses further indicated that work-family conflict fully explained the caregiver strain experienced by men, while it only partially accounted for caregiver strain among women. These results extend previous research that has documented differences in the duties and experiences of men and women caregivers. We discuss direct empathetic crossover as a potential contributory factor for women’s caregiving strain.

Little is known about the intellectual journey of advanced undergraduates engaged in the research process. Moreover, few studies of this population of library users include students' personal essays as a point of analysis in their scholarly pursuits. To gain insights into the research trajectory of apprentice researchers at the University of Michigan, the Library examined the personal essays that students submitted for its inaugural undergraduate research award. These essays chronicled students' intellectual growth and development throughout the research process. Drawing on observations about the unique needs of these students, the authors analyze the implications for library instruction and services.

Background Both sensory and cognitive deficits have been associated with prenatal exposure to alcohol; however, very few studies have focused on sensory deficits in preschool-aged children. As sensory skills develop early, characterization of sensory deficits using novel imaging methods may reveal important neural markers of prenatal alcohol exposure. Methods Participants in this study were 10 children with a fetal alcohol spectrum disorder (FASD) and 15 healthy control (HC) children aged 3 to 6 years. All participants had normal hearing as determined by clinical screens. We measured their neurophysiological responses to auditory stimuli (1,000 Hz, 72 dB tone) using magnetoencephalography (MEG). We used a multidipole spatio-temporal modeling technique to identify the location and timecourse of cortical activity in response to the auditory tones. The timing and amplitude of the left and right superior temporal gyrus sources associated with activation of left and right primary/secondary auditory cortices were compared across groups. Results There was a significant delay in M100 and M200 latencies for the FASD children relative to the HC children (p = 0.01), when including age as a covariate. The within-subjects effect of hemisphere was not significant. A comparable delay in M100 and M200 latencies was observed in children across the FASD subtypes. Conclusions Auditory delay revealed by MEG in children with FASDs may prove to be a useful neural marker of information processing difficulties in young children with prenatal alcohol exposure. The fact that delayed auditory responses were observed across the FASD spectrum suggests that it may be a sensitive measure of alcohol-induced brain damage. Therefore, this measure in conjunction with other clinical tools may prove useful for early identification of alcohol affected children, particularly those without dysmorphia.

A patent data base of 6.7 million compounds generated by a very high performance computer (Blue Gene) requires new techniques for exploitation when extensive use of chemical similarity is involved. Such exploitation includes the taxonomic classification of chemical themes, and data mining to assess mutual information between themes and companies. Importantly, we also launch candidates that evolve by "natural selection" as failure of partial match against the patent data base and their ability to bind to the protein target appropriately, by simulation on Blue Gene. An unusual feature of our method is that algorithms and workflows rely on dynamic interaction between match-and-edit instructions, which in practice are regular expressions. Similarity testing by these uses SMILES strings and, less frequently, graph or connectivity representations. Examining how this performs in high throughput, we note that chemical similarity and novelty are human concepts that largely have meaning by utility in specific contexts. For some purposes, mutual information involving chemical themes might be a better concept.

Mu rhythm is an idling rhythm that originates in the sensorimotor cortex during rest. The frequency of mu rhythm, which is well established in adults, is 8–12 Hz, whereas the limited results available from children suggest a frequency as low as 5.4 Hz at 6 months of age, which gradually increases to the adult value. Understanding the normal development of mu rhythm has important theoretical and clinical implications since we still know very little about this signal in infants and how it develops with age. We measured mu rhythm over the left hemisphere using a pediatric magnetoencephalography (MEG) system in 25 infants (11–47 weeks), 18 preschool children (2–5 years) and 6 adults (20–39 years) for two 5-min sessions during two intermixed conditions: a rest condition in which the hands were at rest, and a prehension condition in which the subject squeezed a pipette with his/her right hand. In all participants, mu rhythm was present over the frontoparietal area during the rest condition, but was clearly suppressed during the prehension condition. Mu rhythm peak frequency, determined from the amplitude spectra, increased rapidly as a function of age from 2.75 Hz at 11 weeks to 8.25 Hz at 47 weeks (r2 = 0.83). It increased very slowly during the preschool period (3.1 ± 0.9 years; 8.5 ± 0.54 Hz). The frequency in these children was, however, lower than in adults (10.3 ± 1.2 Hz). Our results show a rapid maturation in spontaneous mu rhythm during the first year of life.

EUDOC™ is a molecular docking program that has successfully helped to identify new drug leads. This virtual screening (VS) tool identifies drug candidates by computationally testing the binding of these drugs to biologically important protein targets. This approach can reduce the research time required of biochemists, accelerating the identification of therapeutically useful drugs and helping to transfer discoveries from the laboratory to the patient. Migration of the EUDOC application code to the IBM Blue Gene/L™ (BG/L) supercomputer has been highly successful. This migration led to a 200-fold improvement in elapsed time for a representative VS application benchmark. Three focus areas provided benefits. First, we enhanced the performance of serial code through application redesign, hand-tuning, and increased usage of SIMD (single-instruction, multiple-data) floating-point unit operations. Second, we studied computational load-balancing schemes to maximize processor utilization and application scalability for the massively parallel architecture of the BG/L system. Third, we greatly enhanced system I/O interaction design. We also identified and resolved severe performance bottlenecks, allowing for efficient performance on more than 4,000 processors. This paper describes specific improvements in each of the areas of focus.

Bioinformatics databases used for sequence comparison and sequence alignment are growing exponentially. This has popularized programs that carry out database searches. Current implementations of sequence alignment methods based on hidden Markov models (HMM) have proven to be computationally intensive and, hence, amenable to architectures with multiple processors. In this paper, we describe a modified version of the original parallel implementation of HMMs on a massively parallel system. This is part of the HMMER bioinformatics code. HMMER 2.3.2 uses profile HMMs for sensitive database searching based on statistical descriptions of a sequence family's consensus (Durbin et al., 1998), Two of the nine programs were further parallelized to take advantage of the large number of processors, namely, hmmsearch and hmmpfam. For our study, we start by porting the parallel virtual machine (PVM) versions of these two programs currently available as part of the HMMER suite of programs. We report the performance of these nonoptimized versions as baselines. Our work also includes the introduction of an alternate sequence file indexing, multiple-master configuration, dynamic data collection and, finally, load balancing via the indexed sequence files. This set of optimizations constitutes our modified version for massively parallel systems. Our results show parallel performance improvements of more than one order of magnitude (16 times) for hmmsearch and hmmpfam.

Heart disease is the number one killer in the United States, and finding indicators of the disease at an early stage is critical for treatment and prevention. In this paper we evaluate visualization techniques that enable the diagnosis of coronary artery disease. A key physical quantity of medical interest is endothelial shear stress (ESS). Low ESS has been associated with sites of lesion formation and rapid progression of disease in the coronary arteries. Having effective visualizations of a patient's ESS data is vital for the quick and thorough non-invasive evaluation by a cardiologist. We present a task taxonomy for hemodynamics based on a formative user study with domain experts. Based on the results of this study we developed HemoVis, an interactive visualization application for heart disease diagnosis that uses a novel 2D tree diagram representation of coronary artery trees. We present the results of a formal quantitative user study with domain experts that evaluates the effect of 2D versus 3D artery representations and of color maps on identifying regions of low ESS. We show statistically significant results demonstrating that our 2D visualizations are more accurate and efficient than 3D representations, and that a perceptually appropriate color map leads to fewer diagnostic mistakes than a rainbow color map.

A new technique for best effort delivery of broadcast bursty multi-slot messages is investigated, using random access with capture. It is shown that a combination of packet level coding and random spreading of a message's packets can improve message reception probability, satisfaction of delay constraints, and throughput in many cases. Furthermore, we show how the specific transmission strategy employed should depend on the message length, total offered traffic, and the specific delay constraints. In addition, we show how edge effects, the finite size of the network, and receiver capture significantly impact performance not only at the edges of the network, but also near the center of the network. Finally, we demonstrate how to leverage these edge effects so that the introduction of minimal feedback from only one or two nodes can substantially improve the probability of message reception for all nodes in the network.

Optimal resource allocations for best effort delivery of broadcasting bursty multi-slots messages with random access are investigated. We consider broadcast multi-slot messages originating from all nodes in wireless random access networks of varying sizes, with receivers employing capture. Allocation of both access probabilities and transmission energy needed for sending various amounts of coded packets are investigated. The distributed transmitters must cooperate by Duly using the resources They are allocated, so as not to cause additional collisions that would diminish the performance of the other users. We evaluate resource allocation schemes in terms of message loss probability, throughput, and probability of satisfaction of specific delay constraints. It is demonstrated that optimal strategies for these metrics depend on the total offered traffic, the number of nodes, and the capture effect. It is shown how the optimal throughput can be implemented with finite delay. Furthermore, we show how even in large networks with the optimal allocation strategy, edge effects and capture significantly impact performance not only at the edges of the network, but also in the center of the network. Finally, we demonstrate how the addition of minimal feedback and further cooperation to the optimal best effort delivery strategy can significantly increase the probability of 'reception for all nodes.

We present the first large-scale simulation of blood flow in the coronary artieries and other vessels supplying blood to the heart muscle, with a realistic description of human arterial geometry at spatial resolutions from centimeters down to 10 microns (near the size of red blood cells). This multiscale simulation resolves the fluid into a billion volume units, embedded in a bounding space of 300 billion voxels, coupled with the concurrent motion of 300 million red blood cells, which interact with one another and with the surrounding fluid. The level of detail is sufficient to describe phenomena of potential physiological and clinical significance, such as the development of atherosclerotic plaques. The simulation achieves excellent scalability on up to 294, 912 Blue Gene/P computational cores.

In the life sciences, genomic databases for sequence search have been growing exponentially in size. As a result, faster sequence-search algorithms to search these databases continue to evolve to cope with algorithmic time complexity. The ubiquitous tool for such search is the Basic Local Alignment Search Tool (BLAST) [1] from the National Center for Biotechnology Information (NCBI). Despite continued algorithmic improvements in BLAST, it cannot keep up with the rate at which the database is exponentially increasing in size. Therefore, parallel implement-ations such as mpiBLAST have emerged to address this problem. The performance of such implementations depends on a myriad of factors including algorithmic, architectural, and mapping of the algorithm to the architecture. This paper describes modifications and extensions to a parallel and distributed-memory version of BLAST called mpiBLAST-PIO and how it maps to a massively parallel system, specifically IBM Blue Gene/L (BG/L). The extensions include a virtual file manager, a "multiple master" run-time model, efficient fragment distribution, and intelligent load balancing. In this study, we have shown that our optimized mpiBLAST-PIO on BG/L using a query with 28014 sequences and the NR and NT databases scales to 8192 nodes (two cores per node). The cases tested here are well suited for a massively parallel system.

The EUDOC application code was ported to and optimized for the IBM eServer Blue Gene (BG/L) supercomputer. EUDOC is a molecular docking program that has shown success predicting drug-bound protein complexes and identifying new drug leads. Single node performance was optimized to obtain a 4X improvement by handtuning critical sections of code. Many of the techniques used are applicable to other applications running on BG/L. Load balancing schemes were studied to maximize processor utilization and scalability of the application. A static load balance scheme achieves 40% processor utilization, while a head-tailtail scheme that takes better advantage of the high-speed interconnect on BG/L peaked above 98%. Performance results are shown using 512 and 2048 processors on two different drug targets with a database of 65536 "drug-like" molecules. The results suggest linear scaling. We will show how EUDOC was optimized to obtain this speedup, and present the load balancing results.