Precision medicine for psychotic disorders: objective assessment, risk prediction, and pharmacogenomics.

Psychosis occurs inside the brain, but may have external manifestations (peripheral molecular biomarkers, behaviors) that can be objectively and quantitatively measured. Blood biomarkers that track core psychotic manifestations such as hallucinations and delusions could provide a window into the biology of psychosis, as well as help with diagnosis and treatment. We endeavored to identify objective blood gene expression biomarkers for hallucinations and delusions, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We were successful in identifying biomarkers that were predictive of high hallucinations and of high delusions states, and of future psychiatric hospitalizations related to them, more so when personalized by gender and diagnosis. Top biomarkers for hallucinations that survived discovery, prioritization, validation and testing include PPP3CB, DLG1, ENPP2, ZEB2, and RTN4. Top biomarkers for delusions include AUTS2, MACROD2, NR4A2, PDE4D, PDP1, and RORA. The top biological pathways uncovered by our work are glutamatergic synapse for hallucinations, as well as Rap1 signaling for delusions. Some of the biomarkers are targets of existing drugs, of potential utility in pharmacogenomics approaches (matching patients to medications, monitoring response to treatment). The top biomarkers gene expression signatures through bioinformatic analyses suggested a prioritization of existing medications such as clozapine and risperidone, as well as of lithium, fluoxetine, valproate, and the nutraceuticals omega-3 fatty acids and magnesium. Finally, we provide an example of how a personalized laboratory report for doctors would look. Overall, our work provides advances for the improved diagnosis and treatment for schizophrenia and other psychotic disorders.

Probing the energetic particle environment near the Sun.

NASA's Parker Solar Probe mission1 recently plunged through the inner heliosphere of the Sun to its perihelia, about 24 million kilometres from the Sun. Previous studies farther from the Sun (performed mostly at a distance of 1 astronomical unit) indicate that solar energetic particles are accelerated from a few kiloelectronvolts up to near-relativistic energies via at least two processes: 'impulsive' events, which are usually associated with magnetic reconnection in solar flares and are typically enriched in electrons, helium-3 and heavier ions2, and 'gradual' events3,4, which are typically associated with large coronal-mass-ejection-driven shocks and compressions moving through the corona and inner solar wind and are the dominant source of protons with energies between 1 and 10 megaelectronvolts. However, some events show aspects of both processes and the electron-proton ratio is not bimodally distributed, as would be expected if there were only two possible processes5. These processes have been very difficult to resolve from prior observations, owing to the various transport effects that affect the energetic particle population en route to more distant spacecraft6. Here we report observations of the near-Sun energetic particle radiation environment over the first two orbits of the probe. We find a variety of energetic particle events accelerated both locally and remotely including by corotating interaction regions, impulsive events driven by acceleration near the Sun, and an event related to a coronal mass ejection. We provide direct observations of the energetic particle radiation environment in the region just above the corona of the Sun and directly explore the physics of particle acceleration and transport.

Understanding physician preferences about combined thrombolysis and thrombectomy in patients with large vessel occlusion: An international cross-sectional survey.

BACKGROUND: A recently published individual participant-level meta-analysis found that EVT alone was not non-inferior to combined intravenous thrombolysis (IVT) and EVT. Our aim was to determine factors that influence physicians' treatment choice of IVT-alone versus EVT-alone versus a combined approach. METHODS: We performed an international, structured, invite-only survey among physicians treating patients presenting with AIS. Respondents were asked 16 multiple choice questions. Fourteen questions involved the respondent being provided with a clinical scenario. In each scenario, a patient was presenting with an AIS with LVO, varying a single clinical or imaging feature. RESULTS: A total of 282 stroke physicians (mean age 46 years, 75 % males) participated in the survey. In LVO stroke, eligible for both IVT and EVT, without other qualifiers, 220 (85.9 %) respondents chose to pursue a combined approach. For age over 80 years, 191 (74 %) participants opted for combined approach, which decreased to 121 (48.2 %) with dementia and 148 (57.4 %) if the patient was on dual anti-platelet therapy (DAPT). Of respondents choosing combination therapy in a patient above the age of 80, only 105 (56.8 %) would pursue the same in a patient with dementia. For imaging factors, 177 (72.8 %) opted for a combined approach for intracranial carotid occlusion, which decreased to 160 (65.3 %) in tandem occlusions. Overall, 88 (38 %) respondents agreed to the statement "I am uncomfortable with uncertainty in patient care". CONCLUSIONS: In a typical patient with AIS due to LVO, most respondents still choose a combined revascularization approach but discrepancy in decision-making increases in complex scenarios.

The development of international wound debridement best practice recommendations: Consensus between nurses specialized in Wound, Ostomy and Continence Canada and the society of tissue viability.

Debridement is an important component of wound management and can improve outcomes for patients. Debridement needs to be done by an appropriately trained health professional, but the scope of practice, credentials, training, competencies, and regulatory requirements regarding wound debridement can differ. Best Practice Recommendations were created to positively influence patient safety related to all methods of debridement, across the continuum of care, and to be implemented widely by nurses at all professional levels in Canada. AIM: To further develop the Best Practice Recommendations for wound debridement, with an international perspective, by creating a consensus document to support the global adoption of evidence-based debridement practice for health professionals. METHODS: A consensus meeting utilising Delphi methods was conducted between the authors to review the consensus statements. Once 80 % agreement was achieved, a wide range of wound care experts were identified by the authors and invited to participate in an external review of the statements. RESULTS: Fifteen consensus statements about wound debridement were agreed upon and are presented in this paper. CONCLUSIONS: These best practice recommendations have been reviewed by a wide range of practitioners from across the UK and Canada and aim to provide guidance on the standardisation of debridement practices for healthcare professionals.

Deconstructing sex: Strategies for undoing binary thinking in neuroendocrinology and behavior.

The scientific community widely recognizes that "sex" is a complex category composed of multiple physiologies. Yet in practice, basic scientific research often treats "sex" as a single, internally consistent, and often binary variable. This practice occludes important physiological factors and processes, and thus limits the scientific value of our findings. In human-oriented biomedical research, the use of simplistic (and often binary) models of sex ignores the existence of intersex, trans, non-binary, and gender non-conforming people and contributes to a medical paradigm that neglects their needs and interests. More broadly, our collective reliance on these models legitimizes a false paradigm of human biology that undergirds harmful medical practices and anti-trans political movements. Herein, we continue the conversations begun at the SBN 2022 Symposium on Hormones and Trans Health, providing guiding questions to help scientists deconstruct and rethink the use of "sex" across the stages of the scientific method. We offer these as a step toward a scientific paradigm that more accurately recognizes and represents sexed physiologies as multiple, interacting, variable, and unbounded by gendered preconceptions. We hope this paper will serve as a useful resource for scientists who seek a new paradigm for researching and understanding sexed physiologies that improves our science, widens the applicability of our findings, and deters the misuse of our research against marginalized groups.

Multiple staging investigations may not change management in patients with high-grade dysplasia or early esophageal adenocarcinoma.

The clinical value of multiple staging investigations for high-grade dysplasia or early adenocarcinoma of the esophagus is unclear. A single-center prospective cohort of patients treated for early esophageal cancer between 2000 and 2019 was analyzed. This coincided with a transition period from esophagectomy to endoscopic mucosal resection (EMR) as the treatment of choice. Patients were staged with computed tomography (CT), endoscopic ultrasound (EUS) and 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography(PET)/CT. The aim of this study was to assess their accuracy and impact on clinical management. 297 patients with high-grade dysplasia or early adenocarcinoma were included (endoscopic therapy/EMR n = 184; esophagectomy n = 113 [of which a 'combined' group had surgery preceded by endoscopic therapy n = 23]). Staging accuracy was low (accurate staging EMR: CT 40.1%, EUS 29.6%, FDG-PET/CT 11.0%; Esophagectomy: CT 43.3%, EUS 59.7%, FDG-PET/CT 29.6%; Combined: CT 28.6%, EUS46.2%, FDG-PET/CT 30.0%). Staging inaccuracies across all groups that could have changed management by missing T2 disease were CT 12%, EUS 12% and FDG-PET/CT 1.6%. The sensitivity of all techniques for detecting nodal disease was low (CT 12.5%, EUS 12.5%, FDG-PET/CT0.0%). Overall, FDG-PET/CT and EUS changed decision-making in only 3.2% of patients with an early cancer on CT and low-risk histology. The accuracy of staging with EUS, CT and FDG-PET/CT in patients with high-grade dysplasia or early adenocarcinoma of the esophagus is low. EUS and FDG-PET/CT added relevant staging information over standard CT in very few cases, and therefore, these investigations should be used selectively. Factors predicting the need for esophagectomy are predominantly obtained from EMR histology rather than staging investigations.

Tools for assessing health research partnership outcomes and impacts: a systematic review.

OBJECTIVE: To identify and assess the globally available valid, reliable and acceptable tools for assessing health research partnership outcomes and impacts. METHODS: We searched Ovid MEDLINE, Embase, CINAHL Plus and PsycINFO from origin to 2 June 2021, without limits, using an a priori strategy and registered protocol. We screened citations independently and in duplicate, resolving discrepancies by consensus and retaining studies involving health research partnerships, the development, use and/or assessment of tools to evaluate partnership outcomes and impacts, and reporting empirical psychometric evidence. Study, tool, psychometric and pragmatic characteristics were abstracted using a hybrid approach, then synthesized using descriptive statistics and thematic analysis. Study quality was assessed using the quality of survey studies in psychology (Q-SSP) checklist. RESULTS: From 56 123 total citations, we screened 36 027 citations, assessed 2784 full-text papers, abstracted data from 48 studies and one companion report, and identified 58 tools. Most tools comprised surveys, questionnaires and scales. Studies used cross-sectional or mixed-method/embedded survey designs and employed quantitative and mixed methods. Both studies and tools were conceptually well grounded, focusing mainly on outcomes, then process, and less frequently on impact measurement. Multiple forms of empirical validity and reliability evidence was present for most tools; however, psychometric characteristics were inconsistently assessed and reported. We identified a subset of studies (22) and accompanying tools distinguished by their empirical psychometric, pragmatic and study quality characteristics. While our review demonstrated psychometric and pragmatic improvements over previous reviews, challenges related to health research partnership assessment and the nascency of partnership science persist. CONCLUSION: This systematic review identified multiple tools demonstrating empirical psychometric evidence, pragmatic strength and moderate study quality. Increased attention to psychometric and pragmatic requirements in tool development, testing and reporting is key to advancing health research partnership assessment and partnership science. PROSPERO CRD42021137932.

Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease.

AIMS: REVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up beyond the scheduled study treatment period. METHODS AND RESULTS: A total of 30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy. After stopping the randomly allocated treatment, 26 129 survivors entered a post-trial follow-up period, blind to their original treatment allocation. The primary outcome was first post-randomization major coronary event (i.e. coronary death, myocardial infarction, or coronary revascularization) during the in-trial and post-trial treatment periods, with analysis by intention-to-treat. Allocation to anacetrapib conferred a 9% [95% confidence interval (CI) 3-15%; P = 0.004] proportional reduction in the incidence of major coronary events during the study treatment period (median 4.1 years). During extended follow-up (median 2.2 years), there was a further 20% (95% CI 10-29%; P < 0.001) reduction. Overall, there was a 12% (95% CI 7-17%, P < 0.001) proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% (95% CI 1.0-2.6%) absolute reduction. There were no significant effects on non-vascular mortality, site-specific cancer, or other serious adverse events. Morbidity follow-up was obtained for 25 784 (99%) participants. CONCLUSION: The beneficial effects of anacetrapib on major coronary events increased with longer follow-up, and no adverse effects emerged on non-vascular mortality or morbidity. These findings illustrate the importance of sufficiently long treatment and follow-up duration in randomized trials of lipid-modifying agents to assess their full benefits and potential harms. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 48678192; ClinicalTrials.gov No. NCT01252953; EudraCT No. 2010-023467-18.

Systematic investigation of imprinted gene expression and enrichment in the mouse brain explored at single-cell resolution.

BACKGROUND: Although a number of imprinted genes are known to be highly expressed in the brain, and in certain brain regions in particular, whether they are truly over-represented in the brain has never been formally tested. Using thirteen single-cell RNA sequencing datasets we systematically investigated imprinted gene over-representation at the organ, brain region, and cell-specific levels. RESULTS: We established that imprinted genes are indeed over-represented in the adult brain, and in neurons particularly compared to other brain cell-types. We then examined brain-wide datasets to test enrichment within distinct brain regions and neuron subpopulations and demonstrated over-representation of imprinted genes in the hypothalamus, ventral midbrain, pons and medulla. Finally, using datasets focusing on these regions of enrichment, we identified hypothalamic neuroendocrine populations and the monoaminergic hindbrain neurons as specific hotspots of imprinted gene expression. CONCLUSIONS: These analyses provide the first robust assessment of the neural systems on which imprinted genes converge. Moreover, the unbiased approach, with each analysis informed by the findings of the previous level, permits highly informed inferences about the functions on which imprinted gene expression converges. Our findings indicate the neuronal regulation of motivated behaviours such as feeding and sleep, alongside the regulation of pituitary function, as functional hotspots for imprinting. This adds statistical rigour to prior assumptions and provides testable predictions for novel neural and behavioural phenotypes associated with specific genes and imprinted gene networks. In turn, this work sheds further light on the potential evolutionary drivers of genomic imprinting in the brain.

The Rat Genome Database (RGD) facilitates genomic and phenotypic data integration across multiple species for biomedical research.

Model organism research is essential for discovering the mechanisms of human diseases by defining biologically meaningful gene to disease relationships. The Rat Genome Database (RGD, ( https://rgd.mcw.edu )) is a cross-species knowledgebase and the premier online resource for rat genetic and physiologic data. This rich resource is enhanced by the inclusion and integration of comparative data for human and mouse, as well as other human disease models including chinchilla, dog, bonobo, pig, 13-lined ground squirrel, green monkey, and naked mole-rat. Functional information has been added to records via the assignment of annotations based on sequence similarity to human, rat, and mouse genes. RGD has also imported well-supported cross-species data from external resources. To enable use of these data, RGD has developed a robust infrastructure of standardized ontologies, data formats, and disease- and species-centric portals, complemented with a suite of innovative tools for discovery and analysis. Using examples of single-gene and polygenic human diseases, we illustrate how data from multiple species can help to identify or confirm a gene as involved in a disease and to identify model organisms that can be studied to understand the pathophysiology of a gene or pathway. The ultimate aim of this report is to demonstrate the utility of RGD not only as the core resource for the rat research community but also as a source of bioinformatic tools to support a wider audience, empowering the search for appropriate models for human afflictions.

Effect of sex and fatigue on quiet standing and dynamic balance and lower extremity muscle stiffness.

PURPOSE: The purpose of the present study was to determine whether there are sex differences in fatigue-induced changes in quiet standing and dynamic balance and establish whether changes in muscle torque and resting stiffness may explain the potential sex differences in balance responses. METHODS: Sixteen recreationally active men (age; 24.8 ± 5.0 years, height; 178.2 ± 5.6 cm, mass; 77.8 ± 13.2 kg) and 10 women (age; 21.0 ± 1.6 years, height; 167 ± 5.3 cm, mass; 61.3 ± 8.9 kg) were assessed for postural sway, Y balance test performance, isokinetic and isometric knee extensor torque and resting stiffness of the vastus lateralis (VL), gastrocnemius lateralis (GL) and Achilles tendon (AT) before and immediately after fatiguing exercise. The fatigue protocol consisted of five sets of 20-drop jumps. RESULTS: The fatiguing exercise elicited similar magnitude (effects size; ES) reductions in muscle torque (men; ES = 0.45-0.80, women; ES = 0.46-0.52), dynamic balance (men; ES = 0.45-0.74, women; ES = 0.47-0.79) and resting VL stiffness (men; ES = 0.46, women; ES = 0.36) in men and women (all p < 0.05). For quiet standing balance, fatigue induced an increase in postural sway metrics (ES = 0.64-1.28) and reduction in resting GL stiffness (ES = 0.40) in men (both p < 0.001) but not women (p > 0.05). CONCLUSION: Fatiguing exercise, when producing a similar level of force reduction, induces similar magnitude reductions in dynamic postural control and resting VL stiffness in men and women. Distinct deteriorations in quiet standing balance in men but not women were accompanied by modifications in calf muscle stiffness following exercise-induced muscle fatigue.

Hemodynamic changes associated with neuraxial anesthesia in pregnant women with covid 19 disease: a retrospective case-control study.

BACKGROUND: Neuraxial blocks is the recommended mode of analgesia and anesthesia in parturients with Coronavirus 19 (COVID-19). There is limited data on the hemodynamic responses to neuraxial blocks in COVID-19 patients. We aim to compare the hemodynamic responses to neuraxial blocks in COVID-19 positive and propensity-matched COVID-19 negative parturients. METHODS: We conducted retrospective, cross-sectional case-control study of hemodynamic changes associated with neuraxial blocks in COVID-19 positive parturients in a Tertiary care academic medical center. Fifty-one COVID-19 positive women confirmed by nasopharyngeal reverse transcription-polymerase chain reaction (RT-PCR), were compared with propensity-matched COVID negative controls (n = 51). Hemodynamic changes after neuraxial block were recorded by electronic medical recording system and analyzed using paired and unpaired T- test and Wilcoxon-Mann-Whitney Rank Sum tests. The primary outcome was ≥ 20% change in MAP and HR after neuraxial block placement. RESULTS: In the epidural group, 7% COVID-19 positive parturients had > 20% decrease in mean arterial pressure (MAP) from baseline compared to 15% COVID-19 negative parturients (P = 0.66). In the spinal group, 83% of COVID-19 positive parturients had a decrease in MAP more than 20% from baseline compared to 71% in control (P = 0.49). MAP drop of more than 40% occurred in 29% COVID positive parturients in the spinal group versus 17% in COVID-19 negative parturients (P = 0.5465). In COVID-19 positive spinal group, 54% required vasopressors whereas 38% in COVID-19 negative spinal group required vasopressors (P = 0.387). We found a significant correlation between body mass index (BMI) > 30 and hypotension in COVID ( +) parturient with odds ratio (8.63; 95% CI-1.93 - 37.21) (P = 0.007). CONCLUSION: Incidence and severity of hypotension after neuraxial blocks were similar between COVID-19 positive and COVID-19 negative parturients. BMI > 30 was a significant risk factor for hypotension as described in preexisting literature, this correlation was seen in COVID-19 positive parturients. The likely reason for parturients with BMI > 30 in COVID negative patients not showing similar correlation, is that the sample size was small.

Whole-beam self-focusing in fusion-relevant plasma.

Fast ignition inertial confinement fusion requires the production of a low-density channel in plasma with density scale-lengths of several hundred microns. The channel assists in the propagation of an ultra-intense laser pulse used to generate fast electrons which form a hot spot on the side of pre-compressed fusion fuel. We present a systematic characterization of an expanding laser-produced plasma using optical interferometry, benchmarked against three-dimensional hydrodynamic simulations. Magnetic fields associated with channel formation are probed using proton radiography, and compared to magnetic field structures generated in full-scale particle-in-cell simulations. We present observations of long-lived, straight channels produced by the Habara-Kodama-Tanaka whole-beam self-focusing mechanism, overcoming a critical barrier on the path to realizing fast ignition. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.

Preparations for a European R&D roadmap for an inertial fusion demo reactor.

A European consortium of 15 laboratories across nine nations have worked together under the EUROFusion Enabling Research grants for the past decade with three principle objectives. These are: (a) investigating obstacles to ignition on megaJoule-class laser facilities; (b) investigating novel alternative approaches to ignition, including basic studies for fast ignition (both electron and ion-driven), auxiliary heating, shock ignition, etc.; and (c) developing technologies that will be required in the future for a fusion reactor. A brief overview of these activities, presented here, along with new calculations relates the concept of auxiliary heating of inertial fusion targets, and provides possible future directions of research and development for the updated European Roadmap that is due at the end of 2020. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.

Role of inflammasome activation in tumor immunity triggered by immune checkpoint blockers.

Immune checkpoint blockers improve the overall survival of a limited number of patients among different cancers. Identifying pathways that influence the immunological and clinical response to treatment is critical to improve the therapeutic efficacy and predict clinical responses. Recently, a key role has been assigned to innate immune mechanisms in checkpoint blockade-driven anti-tumor responses. However, inflammatory pathways can both improve and impair anti-tumor immunity. In this review, we discuss how different inflammatory pathways, particularly inflammasome activation, can influence the clinical outcome of immune checkpoint blockers. Inflammasome activation may reinforce anti-tumor immunity by boosting CD8+ T cell priming as well as by enhancing T helper type 17 (Th17) responses. In particular, we focus on the modulation of the cation channel transmembrane protein 176B (TMEM176B) and the ectonucleotidase CD39 as potential targets to unleash inflammasome activation leading to reinforced anti-tumor immunity and improved efficacy of immune checkpoint blockers. Future studies should be aimed at investigating the mechanisms and cell subsets involved in inflammasome-driven anti-tumor responses.

NYX-458 Improves Cognitive Performance in a Primate Parkinson's Disease Model.

BACKGROUND: NYX-458 is a N-methyl-d-aspartate receptor (NMDAR) modulator that enhances synaptic plasticity. Dopaminergic cell loss in Parkinson's disease (PD) leads to NMDAR dysregulation in the cortico-striato-pallidal-thalmo-cortical network and altered plasticity in brain regions important to cognitive function. We hypothesize that targeting the NMDAR may be an efficacious approach to treating cognitive impairment in PD. OBJECTIVES: NYX-458 was evaluated in 2 nonhuman primate models of PD. The first, a chronic low-dose 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-administration model, was used to assess the effects of NYX-458 on cognitive domains impacted early in PD including attention, working memory, executive function, and visuospatial learning. The second, a high-dose MPTP-administration model, was used to assess potential for NYX-458 induced change in motor symptoms. METHODS: NYX-458 was evaluated in the chronic low-dose MPTP model using the variable delayed response measure to assess attention and working memory and simple discrimination reversal to assess executive function. NYX-458 was also assessed in the high-dose MPTP model as a monotherapy and in combination with low-dose or high-dose levodopa to assess potential impact on motor symptoms. RESULTS: NYX-458 administration resulted in rapid and long-lasting improvement in cognitive function across the domains of attention, working memory, and executive function. Dose levels effective in improving cognitive performance had no effect on PD motor symptoms, the antiparkinsonian benefit of levodopa, or dyskinesia. CONCLUSIONS: NYX-458 provides benefit in specific domains known to be impaired in PD in a dopamine depletion model of PD-like cognitive impairment. These data support the continued evaluation of NYX-458 as a potential therapeutic for cognitive decline in PD. © 2020 International Parkinson and Movement Disorder Society.

Correction to: The validity and reproducibility of perceptually regulated exercise responses during combined arm + leg cycling.

The original version of this article unfortunately contained a mistake.

The validity and reproducibility of perceptually regulated exercise responses during combined arm + leg cycling.

PURPOSE: Rating of perceived exertion (RPE) is a reliable method of assessing exercise intensity during isolated arm and leg cycling. The aim of this study was to assess the validity and reproducibility of perceptually regulated exercise responses during combined arm + leg cycling. METHODS: Twelve males (age; 24.6 ± 5.3 years, height; 1.81 ± 0.7 m, mass; 83.1 ± 8.4 kg) initially undertook incremental exercise tests to volitional exhaustion for arm cycling (133 ± 14 W) and leg cycling (253 ± 32 W). On three subsequent occasions, participants undertook combined arm + leg cycling trials using two modified Monark ergometers involving three bouts of exercise at RPE 9, 13 and 17, in that order. Heart rate (HR), oxygen uptake ([Formula: see text]) and pulmonary ventilation ([Formula: see text]) were recorded continuously. RESULTS: No significant differences were observed for HR (P = 0.086), [Formula: see text] (P = 0.525) and [Formula: see text] (P = 0.899) between trials, whilst significant differences were observed between each level of RPE (all P < 0.001). For % peak [Formula: see text], the ICC increased with successive trials for all RPE levels. For % maximal HR the ICC generally decreased with successive trials. CONCLUSION: RPE can be used as a reliable frame of reference for the production of exercise intensity during combined arm + leg cycling without any formal familiarisation. Since combined arm + leg cycling elicits a greater energy expenditure than arm or leg work alone, this novel mode of non-weight bearing exercise might prove effective for aerobic conditioning and weight control.

Temperature tolerance and humidity requirements of select entomopathogenic fungal isolates for future use in citrus IPM programmes.

Several isolates of Beauveria bassiana (Balsamo-Crivelli) Vuillemin (Hypocreales: Cordycipitacae) and Metarhizium anisopliae (Metchnikoff) Sorokin (Hypocreales: Clavicipitacae) have been investigated as possible microbial control agents of key citrus pests in South Africa. Although laboratory results have been promising, field trials against foliar pests have shown limited success. These findings highlighted the need to investigate other biological attributes of these fungal isolates besides virulence in order to select candidates that may be better suited for the foliar environment. Thus, this study investigated the influence of temperature on the in vitro growth of seven indigenous local isolates and the humidity requirements necessary to promote successful infection, in comparison with two commercial isolates (B. bassiana PPRI 5339 and M. anisopliae ICIPE 69). All the fungal isolates grew across a range of temperatures (8-34 °C) and optimally between 26 and 28 °C. Similarly, fungal infection of Thaumatotibia leucotreta Meyrick (Lepidoptera: Tortricidae) fifth instars occurred across a range of humidity levels (12%, 43%, 75%, 98%) regardless of fungal concentration, although external sporulation was restricted to treatments exposed to 98% relative humidity. It was concluded that neither temperature nor humidity, when considered alone, is likely to significantly influence the efficacy of any of the isolates in the field, given that they are active within temperature and humidity ranges experienced in South African citrus orchards.

Multimodal X-ray imaging of grain-level properties and performance in a polycrystalline solar cell.

The factors limiting the performance of alternative polycrystalline solar cells as compared with their single-crystal counterparts are not fully understood, but are thought to originate from structural and chemical heterogeneities at various length scales. Here, it is demonstrated that multimodal focused nanobeam X-ray microscopy can be used to reveal multiple aspects of the problem in a single measurement by mapping chemical makeup, lattice structure and charge collection efficiency simultaneously in a working solar cell. This approach was applied to micrometre-sized individual grains in a Cu(In,Ga)Se2 polycrystalline film packaged in a working device. It was found that, near grain boundaries, collection efficiency is increased, and that in these regions the lattice parameter of the material is expanded. These observations are discussed in terms of possible physical models and future experiments.