Lower urinary tract symptoms in men: the TRIUMPH cluster RCT.

Background: Conservative therapies are recommended as initial treatment for male lower urinary tract symptoms. However, there is a lack of evidence on effectiveness and uncertainty regarding approaches to delivery. Objective: The objective was to determine whether or not a standardised and manualised care intervention delivered in primary care achieves superior symptomatic outcome for lower urinary tract symptoms to usual care. Design: This was a two-arm cluster randomised controlled trial. Setting: The trial was set in 30 NHS general practice sites in England. Participants: Participants were adult men (aged ≥ 18 years) with bothersome lower urinary tract symptoms. Interventions: Sites were randomised 1 : 1 to deliver the TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions trial intervention or usual care to all participants. The TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions intervention comprised a standardised advice booklet developed for the trial from the British Association of Urological Surgeons' patient information sheets, with patient and expert input. Patients were directed to relevant sections by general practice or research nurses/healthcare assistants following urinary symptom assessment, providing the manualised element. The healthcare professional provided follow-up contacts over 12 weeks to support adherence to the intervention. Main outcome measures: The primary outcome was the validated patient-reported International Prostate Symptom Score 12 months post consent. Rather than the minimal clinically important difference of 3.0 points for overall International Prostate Symptom Score, the sample size aimed to detect a difference of 2.0 points, owing to the recognised clinical impact of individual symptoms. Results: A total of 1077 men consented to the study: 524 in sites randomised to the intervention arm (n = 17) and 553 in sites randomised to the control arm (n = 13). A difference in mean International Prostate Symptom Score at 12 months was found (adjusted mean difference of -1.81 points, 95% confidence interval -2.66 to -0.95 points), with a lower score in the intervention arm, indicating less severe symptoms. Secondary outcomes of patient-reported urinary symptoms, quality of life specific to lower urinary tract symptoms and perception of lower urinary tract symptoms all showed evidence of a difference between the arms favouring the intervention. No difference was seen between the arms in the proportion of urology referrals or adverse events. In qualitative interviews, participants welcomed the intervention, describing positive effects on their symptoms, as well as on their understanding of conservative care and their attitude towards the experience of lower urinary tract symptoms. The interviews highlighted that structured, in-depth self-management is insufficiently embedded within general practitioner consultations. From an NHS perspective, mean costs and quality-adjusted life-years were similar between trial arms. The intervention arm had slightly lower mean costs (adjusted mean difference of -£29.99, 95% confidence interval -£109.84 to £22.63) than the usual-care arm, and a small gain in quality-adjusted life-years (adjusted mean difference of 0.001, 95% confidence interval -0.011 to 0.014). Conclusions: The intervention showed a small, sustained benefit for men's lower urinary tract symptoms and quality of life across a range of outcome measures in a UK primary care setting. Qualitative data showed that men highly valued the intervention. Intervention costs were marginally lower than usual-care costs. Limitations of the study included that trial participants were unmasked, with limited diversity in ethnicity and deprivation level. Additional research is needed to assess the applicability of the intervention for a more ethnically diverse population.. Trial registration: This trial is registered as ISRCTN11669964. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/90/03) and is published in full in Health Technology Assessment; Vol. 28, No. 13. See the NIHR Funding and Awards website for further award information.

Urinary problems among men become more common with age. Nearly one-third of all men aged > 65 years experience some urinary symptoms, which can have a substantial effect on their daily lives. Symptoms include needing to pass urine more often, urgently or during the night, and difficulties in passing urine. Men are usually diagnosed and treated by their general practitioner, and should be offered advice on controlling their symptoms themselves (e.g. lifestyle changes and exercises) before trying tablets or surgery. However, it is not known how helpful such advice is, and how general practices can effectively provide it. Thirty general practices in the West of England and Wessex took part in the study. Practices were split into two groups, with each practice providing either the TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions care package or the practice's usual care to all of its patients in the trial. The TReatIng Urinary symptoms in Men in Primary Healthcare using nonpharmacological and non-surgical interventions care package included a booklet of advice to help control urinary symptoms, with a nurse or healthcare assistant directing men to relevant sections according to their symptoms, and providing follow-up contacts. We mainly assessed the benefits of the TReatIng Urinary symptoms in Men in Primary Healthcare using nonpharmacological and non-surgical interventions care package, compared with usual care, by using a questionnaire on urinary symptoms completed by participants. A total of 1077 men with urinary symptoms that bothered them joined the study. The main result was that men reported greater improvement in urinary symptoms with the TRIUMPH care package than with usual care, 12 months after joining the study. We also found that men receiving the TRIUMPH care package had a slight improvement in quality of life and outlook on their urinary symptoms. There was no difference between the two groups in the number of patients referred to hospital for treatment, the type, number and severity of side effects or cost to the NHS. Overall, the TRIUMPH care package was more effective in treating men with urinary symptoms than usual care by their general practice.

Conducting invasive urodynamics in primary care: qualitative interview study examining experiences of patients and healthcare professionals.

BACKGROUND: Invasive urodynamics is used to investigate the causes of lower urinary tract symptoms; a procedure usually conducted in secondary care by specialist practitioners. No study has yet investigated the feasibility of carrying out this procedure in a non-specialist setting. Therefore, the aim of this study was to explore, using qualitative methodology, the feasibility and acceptability of conducting invasive urodynamic testing in primary care. METHODS: Semi-structured interviews were conducted during the pilot phase of the PriMUS study, in which men experiencing bothersome lower urinary tract symptoms underwent invasive urodynamic testing along with a series of simple index tests in a primary care setting. Interviewees were 25 patients invited to take part in the PriMUS study and 18 healthcare professionals involved in study delivery. Interviews were audio-recorded, transcribed verbatim and analysed using a framework approach. RESULTS: Patients generally found the urodynamic procedure acceptable and valued the primary care setting due to its increased accessibility and familiarity. Despite some logistical issues, facilitating invasive urodynamic testing in primary care was also a positive experience for urodynamic nurses. Initial issues with general practitioners receiving and utilising the results of urodynamic testing may have limited the potential benefit to some patients. Effective approaches to study recruitment included emphasising the benefits of the urodynamic test and maintaining contact with potential participants by telephone. Patients' relationship with their general practitioner was an important influence on study participation. CONCLUSIONS: Conducting invasive urodynamics in primary care is feasible and acceptable and has the potential to benefit patients. Facilitating study procedures in a familiar primary care setting can impact positively on research recruitment. However, it is vital that there is a support network for urodynamic nurses and expertise available to help interpret urodynamic results.

Pressure-Induced Collapse of Magnetic Order in Jarosite.

We report a pressure-induced phase transition in the frustrated kagomé material jarosite at ∼45 GPa, which leads to the disappearance of magnetic order. Using a suite of experimental techniques, we characterize the structural, electronic, and magnetic changes in jarosite through this phase transition. Synchrotron powder x-ray diffraction and Fourier transform infrared spectroscopy experiments, analyzed in aggregate with the results from density functional theory calculations, indicate that the material changes from a R3[over ¯]m structure to a structure with a R3[over ¯]c space group. The resulting phase features a rare twisted kagomé lattice in which the integrity of the equilateral Fe^{3+} triangles persists. Based on symmetry arguments we hypothesize that the resulting structural changes alter the magnetic interactions to favor a possible quantum paramagnetic phase at high pressure.

PRImary care Management of lower Urinary tract Symptoms in men: protocol for development and validation of a diagnostic and clinical decision support tool (the PriMUS study).

INTRODUCTION: Lower urinary tract symptoms (LUTS) is a bothersome condition affecting older men which can lead to poor quality of life. General practitioners (GPs) currently have no easily available assessment tools to help effectively diagnose causes of LUTS and aid discussion of treatment with patients. Men are frequently referred to urology specialists who often recommend treatments that could have been initiated in primary care. GP access to simple, accurate tests and clinician decision tools are needed to facilitate accurate and effective patient management of LUTS in primary care. METHODS AND ANALYSIS: PRImary care Management of lower Urinary tract Symptoms (PriMUS) is a prospective diagnostic accuracy study based in primary care. The study will determine which of a number of index tests used in combination best predict three urodynamic observations in men who present to their GP with LUTS. These are detrusor overactivity, bladder outlet obstruction and/or detrusor underactivity. Two cohorts of participants, one for development of the prototype diagnostic tool and other for validation, will undergo a series of simple index tests and the invasive reference standard (invasive urodynamics). We will develop and validate three diagnostic prediction models based on each condition and then combine them with management recommendations to form a clinical decision support tool. ETHICS AND DISSEMINATION: Ethics approval is from the Wales Research Ethics Committee 6. Findings will be disseminated through peer-reviewed journals and conferences, and results will be of interest to professional and patient stakeholders. TRIAL REGISTRATION NUMBER: ISRCTN10327305.

Longitudinal Reinforcement of Acute Myocardial Infarcts Improves Function by Transmurally Redistributing Stretch and Stress.

A wide range of emerging therapies, from surgical restraint to biomaterial injection to tissue engineering, aim to improve heart function and limit adverse remodeling following myocardial infarction (MI). We previously showed that longitudinal surgical reinforcement of large anterior infarcts in dogs could significantly enhance systolic function without restricting diastolic function, but the underlying mechanisms for this improvement are poorly understood. The goal of this study was to construct a finite element model that could match our previously published data on changes in regional strains and left ventricular function following longitudinal surgical reinforcement, then use the model to explore potential mechanisms for the improvement in systolic function we observed. The model presented here, implemented in febio, matches all the key features of our experiments, including diastolic remodeling strains in the ischemic region, small shifts in the end-diastolic pressure-volume relationship (EDPVR), and large changes in the end-systolic pressure-volume relationship (ESPVR) in response to ischemia and to patch application. Detailed examination of model strains and stresses suggests that longitudinal reinforcement reduces peak diastolic fiber stretch and systolic fiber stress in the remote myocardium and shifts those peaks away from the endocardial surface by reshaping the left ventricle (LV). These findings could help to guide the development of novel therapies to improve post-MI function by providing specific design objectives.

An Isosymmetric High-Pressure Phase Transition in α-Glycylglycine: A Combined Experimental and Theoretical Study.

We investigated the effects of hydrostatic pressure on α-glycylglycine (α-digly) using a combined experimental and theoretical approach. The results of powder X-ray diffraction show a change in compressibility of the axes above 6.7 GPa, but also indicate that the structure remains in the same monoclinic space group, suggesting an isosymmetric phase transition. A noticeable change in the Raman spectra between 6 and 7.5 GPa further supports the observed phase transition. First-principles-based calculations combined with the crystal structure prediction code USPEX predict a number of possible polymorphs at high pressure. An orthorhombic structure with a bent peptide backbone is the lowest enthalpy polymorph above 6.4 GPa; however, it is not consistent with experimental observations. A second monoclinic structure isosymmetric to α-digly, α'-digly, is predicted to become more stable above 11.4 GPa. The partial atomic charges in α'-digly differ from α-digly, and the molecule is bent, possibly indicating different reactivity of α'-digly. The similarity in the lattice parameters predicted from calculations and the axial changes observed experimentally support that the α'-digly phase is likely observed at high pressure. A possible explanation for the isosymmetric phase transition is discussed in terms of relaxing strained hydrogen bonding interactions. Such combined experimental and modeling efforts provide atomic-level insight into how pressure-driven conformational changes alter hydrogen-bonding networks in complicated molecular crystals.

Feasibility of a novel 3-dimensional mathematical algorithmic computation of feline bladder volumes using point-of-care longitudinal and transverse cysto-colic ultrasonographic images.

Conventional geometric formulas for estimating bladder volume assume that bladders have a perfectly uniform spheroid geometry. Bladders are often irregularly shaped, however, especially when under-filled or distorted by a full colon, which results in inaccurate ultrasonographic linear measurements and volume estimation. This pilot study investigates the feasibility, inter-observer reliability (reproducibility), robustness, and agreement of a novel 3-dimensional bladder volume computation method using bladder circumference tracing compared to a published feline linear bladder dimension formula. Paired sets of longitudinal and transverse B-mode bladder ultrasound images (n = 228) were acquired by 2 observers with different point-of-care ultrasonography skills using 10 healthy purpose-bred cats positioned in dorsal recumbency at various time points. Using strict criteria for Lin's concordance correlation coefficient, inter-observer agreements (n = 223) were found to be substantial (0.95 to 0.99) with statistically significant but clinically non-significant median differences (biases) of 0.96 mL [interquartile range (IQR): 0.16 to 2.46, P < 0.001] and 0.23 mL (IQR: 0.88 to 1.97, P = 0.006) when bladder circumference tracings were made on similar sets of ultrasound images respectively. Inter-observer agreements improved from substantial (0.95 to 0.99) to almost perfect (> 0.99) strength-of-agreement as the quality of ultrasound images improved. The bladder circumference tracing method showed moderate (0.90 to 0.95) strength-of-agreement with the recently published feline linear bladder dimension formula, with significant additive median differences (biases) of -6.76 mL (IQR: -9.06 to -3.88, P < 0.001) and -6.44 mL (IQR: -11.41 to -3.81, P < 0.001) recorded by each observer (n = 111, n = 83), respectively. Data obtained from orthogonal ultrasonographic bladder circumference tracings justify further investigation into use of this method for estimating bladder volume in cats.

Les formules géométriques conventionnelles pour estimer le volume de la vessie présument que les vessies ont une géométrie sphéroïde uniforme. Les vessies sont souvent de forme irrégulière, toutefois, spécialement lorsqu'elles ne sont pas remplies complètement ou sont déformées par un côlon rempli, ce qui résulte en des mesures linéaires imprécises par échographie et des estimations erronées de volume. La présente étude pilote a examiné la faisabilité, la fiabilité inter-observateur (reproductibilité), robustesse, et accord d'une nouvelle méthode de computation en 3-D du volume de la vessie en utilisant un traçage de la circonférence de la vessie comparée à une formule publiée utilisant la dimension linéaire de la vessie féline. Des images échographiques en mode B pairées longitudinale et transverse de la vessie (n = 228) furent obtenues par deux observateurs avec des compétences différentes en échographie au point de service en utilisant 10 chats en santé positionnés en décubitus dorsal à différents moments. En utilisant des critères stricts pour le coefficient de corrélation de concordance de Lin, les accords inter-observateurs (n = 223) ont été notés comme substantiels (0,95 à 0,99) avec une différence médiane (biais) statistiquement significative mais cliniquement non-significative de 0,96 mL [écart interquartile (IQR) : 0,16 à 2,46, P < 0,001] et 0,23 mL (IQR : 0,88 à 1,97, P = 0,006) lorsque les traçages de la circonférence de la vessie étaient effectués sur des groupes similaires d'images échographiques respectivement. La force des accords inter-observateurs se sont améliorés de substantiels (0,95 à 0,99) jusqu'à presque parfaits (> 0,99) à mesure que la qualité des images échographiques s'améliorait. La méthode de traçage de la circonférence de la vessie a montré une force d'accord modérée (0,90 à 0,95) avec la formule récemment publiée des dimensions linéaires de la vessie, avec une différence médiane (biais) additive significative de −6,76 mL (IQR : −9,06 à −3,88, P < 0,001) et −6,44 mL (IQR : −11,41 à −3,81, P < 0,001) notée par chaque observateur (n = 111, n = 83), respectivement. Les données obtenues par traçage orthogonal de la circonférence de la vessie justifient des études supplémentaires sur l'utilisation de cette méthode pour estimer le volume de la vessie chez les chats.(Traduit par Docteur Serge Messier).

Discovery of Cu3Pb.

Materials discovery enables both realization and understanding of new, exotic, physical phenomena. An emerging approach to the discovery of novel phases is high-pressure synthesis within diamond anvil cells, thereby enabling in situ monitoring of phase formation. Now, the discovery via high-pressure synthesis of the first intermetallic compound in the Cu-Pb system, Cu3Pb is reported. Cu3Pb is notably the first structurally characterized mid- to late-first-row transition-metal plumbide. The structure of Cu3Pb can be envisioned as a direct mixture of the two elemental lattices. From this new framework, we gain insight into the structure as a function of pressure and hypothesize that the high-pressure polymorph of lead is a possible prerequisite for the formation of Cu3Pb. Crucially, electronic structure computations reveal band crossings near the Fermi level, suggesting that chemically doped Cu3Pb could be a topologically nontrivial material.

Impact of Pressure on Magnetic Order in Jarosite.

Jarosite, a mineral with a kagomé lattice, displays magnetic frustration yet orders magnetically below 65 K. As magnetic frustration can engender exotic physical properties, understanding the complex magnetism of jarosite comprises a multidecade interdisciplinary challenge. Unraveling the nature of the disparate magnetic coupling interactions that lead to magnetic order in jarosite remains an open question. Specifically, there is no observed trend in the interlayer spacing with magnetic order. Similarly, the relationship between metal-ligand bond distance and magnetic order remains uninvestigated. Here, we use applied pressure to smoothly vary jarosite's structure without manipulating the chemical composition, enabling a chemically invariant structure-function study. Using single-crystal and powder X-ray diffraction, we show that high applied pressures alter both the interlayer spacing and the metal-ligand bond distances. By harnessing a suite of magnetic techniques under pressure, including SQUID-based magnetometry, time-resolved synchrotron Mössbauer spectroscopy, and X-ray magnetic circular dichroism, we construct the magnetic phase diagram for jarosite up to 40 GPa. Notably, we demonstrate that the magnetic ordering temperature increases dramatically to 240 K at the highest pressures. Additionally, we conduct X-ray emission spectroscopy, Mössbauer spectroscopy, and UV-visible absorption spectroscopy experiments to comprehensively map the magnetic and electronic structures of jarosite at high pressure. We use these maps to construct chemically pure magnetostructural correlations which fully explain the nature and role of the disparate magnetic coupling interactions in jarosite.

Mental Health and Well-Being in Mothers of Children With Rare Genetic Syndromes Showing Chronic Challenging Behavior: A Cross-Sectional and Longitudinal Study.

It is well documented that mothers of children with challenging behavior (CB) experience elevated levels of stress and that this persists over time, but less is known about the experience of mothers of children with rare genetic syndromes. This article describes 2 studies, 1 cross-sectional and 1 longitudinal, comparing well-being in mothers of children with Angelman, Cornelia de Lange and Cri du Chat syndrome who have either shown chronic CB ( n = 18) or low/no CB ( n = 26) in the preceding 7 years. The presence of chronic, long-term CB increased maternal stress but not depression or anxiety, and did not influence positive well-being. Stress relating specifically to their child's genetic syndrome reduced with age, highlighting the need for further exploration in this area.

Multiparametric CMR imaging of infarct remodeling in a percutaneous reperfused Yucatan mini-pig model.

To further understanding of the temporal evolution and pathophysiology of adverse ventricular remodeling over the first 60 days following a myocardial infarction (MI) in both the infarcted and remote myocardium, we performed multi-parametric cardiac magnetic resonance (CMR) imaging in a closed-chest chronic Yucatan mini-pig model of reperfused MI. Ten animals underwent 90 min left anterior descending artery occlusion and reperfusion. Three animals served as controls. Multiparametric CMR (1.5T) was performed at baseline, Day 2, Day 30 and in four animals on Day 60 after MI. Left ventricular (LV) volumes and infarct size were measured. T1 and T2 mapping sequences were performed to measure values in the infarct and remote regions. Remote region collagen fractions were compared between infarcted animals and controls. Procedure success was 80%. The model created large infarcts (28 ± 5% of LV mass on Day 2), which led to significant adverse myocardial remodeling that stabilized beyond 30 days. Native T1 values did not reliably differentiate remote and infarct regions acutely. There was no evidence of remote fibrosis as indicated by partition coefficient and collagen fraction analyses. The infarct T2 values remained elevated up to 60 days after MI. Multiparametric CMR in this model showed significant adverse ventricular remodeling 30 days after MI similar to that seen in humans. In addition, this study demonstrated that remote fibrosis is absent and that infarct T2 signal remains chronically elevated in this model. These findings need to be considered when designing preclinical trials using CMR endpoints.

Discovery of FeBi2.

Recent advances in high-pressure techniques offer chemists access to vast regions of uncharted synthetic phase space, expanding our experimental reach to pressures comparable to the core of the Earth. These newfound capabilities enable us to revisit simple binary systems in search of compounds that for decades have remained elusive. The most tantalizing of these targets are systems in which the two elements in question do not interact even as molten liquids-so-called immiscible systems. As a prominent example, immiscibility between iron and bismuth is so severe that no material containing Fe-Bi bonds is known to exist. The elusiveness of Fe-Bi bonds has a myriad of consequences; crucially, it precludes completing the iron pnictide superconductor series. Herein we report the first iron-bismuth binary compound, FeBi2, featuring the first Fe-Bi bond in the solid state. We employed geologically relevant pressures, similar to the core of Mars, to access FeBi2, which we synthesized at 30 GPa and 1500 K. The compound crystallizes in the Al2Cu structure type (space group I4/mcm) with a = 6.3121(3) Å and c = 5.4211(4) Å. The new binary intermetallic phase persists from its formation pressure of 30 GPa down to 3 GPa. The existence of this phase at low pressures suggests that it might be quenchable to ambient pressure at low temperatures. These results offer a pathway toward the realization of new exotic materials.

The neglected messengers: Control of cardiac myofilaments by protein phosphatases.

Cardiac myofilaments act as the central contractile apparatus of heart muscle cells. Covalent modification of constituent proteins through phosphorylation is a rapid and powerful mechanism to control myofilament function, and is increasingly seen as a mechanism of disease. While the relationship between protein kinases and cardiac myofilaments has been widely examined, the impact of protein dephosphorylation by protein phosphatases is poorly understood. This review outlines the mechanisms by which the mostly widely expressed protein phosphatases in cardiac myocytes regulate myofilament function, and the emerging role of myofilament-associated protein phosphatases in heart failure. The importance of regulatory subunits and subcellular compartmentalization in determining the functional impact of protein phosphatases on myofilament and myocardial function is also discussed, as are discrepancies about the roles of protein phosphatases in regulating myofilament function. The potential for targeting these molecular messengers in the treatment of heart failure is discussed as a key future direction.

Perceptions of early body image socialization in families: Exploring knowledge, beliefs, and strategies among mothers of preschoolers.

This study sought to explore parental perceptions of body image in preschoolers. We conducted semi-structured interviews with 30 primary caregivers of preschoolers to examine knowledge, beliefs, and strategies regarding early body image socialization in families. Thematic Analysis yielded three themes highlighting knowledge gaps, belief discrepancies, and limited awareness of strategies. Findings regarding knowledge: Most participants defined body image as objective attractiveness rather than subjective self-assessment (53%) and focused on negative body image. Beliefs: Although 97% of participants believed weight and shape impact children's self-esteem, 63% believed preschoolers too young to have a body image. Strategies: Most participants (53%) said family was a primary influence on body image, but identified few effective strategies and 63% said they did not do anything to influence children's body image. Findings suggested family body image socialization in preschoolers is occurring outside the awareness of parents and the concept of positive body image is underdeveloped.

Discovery of a Superconducting Cu-Bi Intermetallic Compound by High-Pressure Synthesis.

A new intermetallic compound, the first to be structurally identified in the Cu-Bi binary system, is reported. This compound is accessed by high-pressure reaction of the elements. Its detailed characterization, physical property measurements, and ab initio calculations are described. The commensurate crystal structure of Cu11 Bi7 is a unique variation of the NiAs structure type. Temperature-dependent electrical resistivity and heat capacity measurements reveal a bulk superconducting transition at Tc =1.36 K. Density functional theory calculations further demonstrate that Cu11 Bi7 can be stabilized (relative to decomposition into the elements) at high pressure and temperature. These results highlight the ability of high-pressure syntheses to allow for inroads into heretofore-undiscovered intermetallic systems for which no thermodynamically stable binaries are known.

Modifying the mechanics of healing infarcts: Is better the enemy of good?

Myocardial infarction (MI) is a major source of morbidity and mortality worldwide, with over 7 million people suffering infarctions each year. Heart muscle damaged during MI is replaced by a collagenous scar over a period of several weeks, and the mechanical properties of that scar tissue are a key determinant of serious post-MI complications such as infarct rupture, depression of heart function, and progression to heart failure. Thus, there is increasing interest in developing therapies that modify the structure and mechanics of healing infarct scar. Yet most prior attempts at therapeutic scar modification have failed, some catastrophically. This article reviews available information about the mechanics of healing infarct scar and the functional impact of scar mechanical properties, and attempts to infer principles that can better guide future attempts to modify scar. One important conclusion is that collagen structure, mechanics, and remodeling of healing infarct scar vary so widely among experimental models that any novel therapy should be tested across a range of species, infarct locations, and reperfusion protocols. Another lesson from past work is that the biology and mechanics of healing infarcts are sufficiently complex that the effects of interventions are often counterintuitive; for example, increasing infarct stiffness has little effect on heart function, and inhibition of matrix metalloproteases (MMPs) has little effect on scar collagen content. Computational models can help explain such counterintuitive results, and are becoming an increasingly important tool for integrating known information to better identify promising therapies and design experiments to test them. Moving forward, potentially exciting new opportunities for therapeutic modification of infarct mechanics include modulating anisotropy and promoting scar compaction.

Physiological Implications of Myocardial Scar Structure.

Once myocardium dies during a heart attack, it is replaced by scar tissue over the course of several weeks. The size, location, composition, structure, and mechanical properties of the healing scar are all critical determinants of the fate of patients who survive the initial infarction. While the central importance of scar structure in determining pump function and remodeling has long been recognized, it has proven remarkably difficult to design therapies that improve heart function or limit remodeling by modifying scar structure. Many exciting new therapies are under development, but predicting their long-term effects requires a detailed understanding of how infarct scar forms, how its properties impact left ventricular function and remodeling, and how changes in scar structure and properties feed back to affect not only heart mechanics but also electrical conduction, reflex hemodynamic compensations, and the ongoing process of scar formation itself. In this article, we outline the scar formation process following a myocardial infarction, discuss interpretation of standard measures of heart function in the setting of a healing infarct, then present implications of infarct scar geometry and structure for both mechanical and electrical function of the heart and summarize experiences to date with therapeutic interventions that aim to modify scar geometry and structure. One important conclusion that emerges from the studies reviewed here is that computational modeling is an essential tool for integrating the wealth of information required to understand this complex system and predict the impact of novel therapies on scar healing, heart function, and remodeling following myocardial infarction.

Effect of Scar Compaction on the Therapeutic Efficacy of Anisotropic Reinforcement Following Myocardial Infarction in the Dog.

Cardiac restraint devices have been used following myocardial infarction (MI) to limit left ventricular (LV) dilation, although isotropic restraints have not been shown to improve post-MI LV function. We have previously shown that anisotropic reinforcement of acute infarcts dramatically improves LV function. This study examined the effects of chronic, anisotropic infarct restraint on LV function and remodeling. Hemodynamics, infarct scar structure, and LV volumes were measured in 28 infarcted dogs (14 reinforced, 14 control). Longitudinal restraint reduced 48-h LV volumes, but no differences in LV volume, function, or infarct scar structure were observed after 8 weeks of healing. All scars underwent substantial compaction during healing; we hypothesize that compaction negated the effects of restraint therapy by mechanically unloading the restraint device. Our results lend support to the concept of adjustable restraint devices and suggest that scar compaction may explain some of the variability in published studies of local infarct restraint.

A novel electronic assessment strategy to support applied Drosophila genetics training in university courses.

The advent of "omic" technologies has revolutionized genetics and created a demand to focus classical genetics on its present-day applications (Redfield, 2012, PLoS Biol 10: e1001356). This demand can be met by training students in Drosophila mating scheme design, which is an important problem-solving skill routinely applied in many modern research laboratories. It promotes a thorough understanding and application of classical genetics rules and introduces to transgenic technologies and the use of model organisms. As we show here, such training can be implemented as a flexible and concise module (~1-day home study, ~8-hour course time) on university courses by using our previously published training package designed for fly researchers (Roote and Prokop, 2013, G3 (Bethesda) 3: 353-358). However, assessing this training to make it an accredited course element is difficult, especially in large courses. Here, we present a powerful assessment strategy based on a novel hybrid concept in which students solve crossing tasks initially on paper and then answer automatically marked questions on the computer (1.5 hours total). This procedure can be used to examine student performance on more complex tasks than conventional e-assessments and is more versatile, time-saving, and fairer than standard paper-based assignments. Our evaluation shows that the hybrid assessment is effective and reliably detects varying degrees of understanding among students. It also may be applicable in other disciplines requiring complex problem solving, such as mathematics, chemistry, physics, or informatics. Here, we describe our strategies in detail and provide all resources needed for their implementation.

(BiSe)1.23CrSe2 and (BiSe)1.22(Cr1.2Se2)2: magnetic anisotropy in the first structurally characterized Bi-Se-Cr ternary compounds.

Compounds containing both heavy main group elements and paramagnetic transition metals form a fertile area for the study of magnetic anisotropy. We pursued the synthesis, characterization, and magnetic measurements of Bi-Se-Cr compounds: a ternary system with no structurally characterized materials. Those efforts led to the isolation of two novel misfit layer compounds, namely, (BiSe)1.23CrSe2 (1) and (BiSe)1.22(Cr1.2Se2)2 (2). The crystal structure of 1 consists of alternating BiSe and CrSe2 layers along the c-axis, and 2 is composed of alternating BiSe and (Cr1.2Se2)2 layers along the c-axis. Lattice mismatch occurs in both compounds along the b-axis and leads to positional modulation of the atoms. Field- and temperature-dependent measurements were performed to assess the degree of magnetic anisotropy. Temperature-dependent susceptibility measurements on aligned crystals of 1 display increased bifurcation of zero-field cooled and field cooled data when crystals are oriented with H perpendicular to c than when the crystals are oriented with H parallel to c. Magnetic anisotropy is less pronounced in 2 where both crystallographic orientations exhibit bifurcation at 26 K. The complexity of the magnetic behavior in both compounds likely signifies a competition between CrSe2 intralayer ferromagnetic coupling and interlayer antiferromagnetic coupling. These results highlight the exciting magnetic properties that can arise from the exploration of new ternary phases.