Temperature contributes to host specialization of coffee wilt disease (Fusarium xylarioides) on arabica and robusta coffee crops

Coffee wilt disease, caused by the fungus Fusarium xylarioides, is a vascular wilt disease that has affected coffee production in sub-Saharan Africa over the past century. Today, the disease has two host-specific populations specialising on arabica and robusta coffee crops, which grow at high and low altitude, respectively. Here we test whether adaptation to different temperatures contributes to specialisation of the fungi on each crop. Firstly, climate models show that the severity of the arabica and robusta populations of coffee wilt disease correlates with temperature. The robusta population shows higher peak severity than the arabica population overall, but the latter has greater cold tolerance. Secondly, growth assays of thermal performance of fungal strains in vitro show that, while robusta strains grow faster than arabicas at intermediate temperatures, the arabica strains have higher sporulation and spore germination rates at temperatures below 15ºC. The match between environmental patterns of severity in nature with thermal performance of fungal cultures in the laboratory supports a role for temperature adaptation in specialisation on arabica and robusta coffee. Extrapolating our temperature-models to future climate change predicts that disease severity could decline on average due to increased temperature but could increase in some coffee-growing regions

The influence of elemental chemistry on the widths of otolith increments in the neon damselfish (Pomacentrus coelestis)

We examined the potential for water chemistry to affect the width of daily increments in reef fish otoliths using both mensurative and manipulative methods. We found significant differences in the widths of increments in otoliths of the neon damselfish (Pomacentrus coelestis) collected in different habitats at One Tree Island on the Great Barrier Reef. We then used manipulative experiments to determine if natural water masses (ocean water vs. lagoon plume) could produce different incremental widths in otoliths in the absence of potentially confounding factors. Fish exposed to ocean water had significantly wider otolith increments for two of the three experiments. Elemental analyses indicated that Ba/Ca ratios were significantly correlated with increment widths for two of the three experiments and Sr/Ca ratios did not correlate with increment width for any experimental period. Variation in crystal-lattice orientation did not explain differences in increment width between treatments. Differences in water chemistry can affect increment widths in otoliths of reef fishes, potentially confounding patterns previously attributed to growth rate or condition alone

Balancing assessment with “In-Service Practical Training”: A case report on collaborative curriculum design for delivery in the practice setting

Three Higher Education Institutions (HEIs) in Ireland are accredited to provide education and training, successful completion of which, entitles one to register as a pharmacist with the Pharmaceutical Society of Ireland (PSI). Legislation (2014) mandated that these HEIs replace their existing structure (four-year degree followed by a one-year internship), with a five-year ‘integrated Master’s programme’. Integration includes ‘in-service practical training’ (placement) at the beginning of Year 4 (four months), and the end of Year 5 (eight months). Year 4 placements do not have to be ‘patient-facing’. Students receive a Bachelor’s degree at the end of Year 4. The Affiliation for Pharmacy Practice Experiential Learning (APPEL), established by the HEIs, manages student placements, training establishments, preceptor training, the preceptors’ competency assessment process, and the virtual learning environment (VLE) that enables delivery of co-developed online modules aligned with placements in Years 4 and 5. This case report aims to describe the process by which this integration has taken place across and within these HEIs and the challenges faced by educators, students, preceptors, and other stakeholders along the way

The effect of sex, menstrual cycle phase and oral contraceptive use on intestinal permeability and ex-vivo monocyte TNFα release following treatment with lipopolysaccharide and hyperthermia

Investigate the impact of sex, menstrual cycle phase and oral contraceptive use on intestinal permeability and ex-vivo tumour necrosis factor alpha (TNFα) release following treatment with lipopolysaccharide (LPS) and hyperthermia. Twenty-seven participants (9 men, 9 eumenorrheic women (MC) and 9 women taking an oral contraceptive pill (OC)) completed three trials. Men were tested on 3 occasions over 6 weeks; MC during early-follicular, ovulation, and mid-luteal phases; OC during the pill and pill-free phase. Intestinal permeability was assessed following a 4-hour dual sugar absorption test (lactulose: rhamnose). Venous blood was collected each trial and stimulated with 100 μg·mL LPS before incubation at 37 °C and 40 °C and analysed for TNFα via ELISA. L:R ratio was higher in OC than MC (+0.003, p = 0.061) and men (+0.005, p = 0.007). Men had higher TNFα responses than both MC (+53 %, p = 0.004) and OC (+61 %, p = 0.003). TNFα release was greater at 40 °C than 37 °C (+23 %, p < 0.001). Men present with lower resting intestinal barrier permeability relative to women regardless of OC use and displayed greater monocyte TNFα release following whole blood treatment with LPS and hyperthermia. Oral contraceptive users had highest intestinal permeability however, neither permeability or TNFα release were impacted by the pill cycle. Although no statistical effect was seen in the menstrual cycle, intestinal permeability and TNFα release were more variable across the phases

Quantitative analysis of high-resolution, contrast-enhanced, cone-beam CT for the detection of intracranial in-stent hyperplasia

BACKGROUND: Intracranial in-stent hyperplasia is a stroke-associated complication that requires routine surveillance. OBJECTIVE: To compare the results of in vivo experiments to determine the accuracy and precision of in-stent hyperplasia measurements obtained with modified C-arm contrast-enhanced, cone-beam CT (CE-CBCT) imaging with those obtained by \u27gold standard\u27 histomorphometry. Additionally, to carry out clinical analyses comparing this CE-CBCT protocol with digital subtraction angiography (DSA). METHODS: A non-binned CE-CBCT protocol (VasoCT) was used that acquires x-ray images with a small field-of-view and applies a full-scale reconstruction algorithm providing high-resolution three-dimensional (3D) imaging with 100 microm isotropic voxels. In an vivo porcine model, VasoCT cross-sectional area measurements were compared with gold standard vessel histology. VasoCT and DSA were used to calculate in-stent stenosis in 23 imaging studies. RESULTS: Porcine VasoCT cross-sectional stent, lumen, and in-stent hyperplasia areas strongly correlated with histological measurements (r(2)=0.97, 0.93, 0.90; slope=1.14, 1.07, and 0.76, respectively; p\u3c0.0001). Clinical VasoCT percentage stenosis correlated well with DSA percentage stenosis (r(2)=0.84; slope=0.76), and the two techniques were free of consistent bias (Bland-Altman, bias=3.29%; 95% CI -14.75% to 21.33%). An illustrative clinical case demonstrated the advantages of VasoCT, including 3D capability and non-invasive IV contrast administration, for detection of in-stent hyperplasia. CONCLUSIONS: C-arm VasoCT is a high-resolution 3D capable imaging technique that has been validated in an animal model for measurement of in-stent tissue growth. Successful clinical implementation of the protocol was performed in a small case series. already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

Dantrolene for the Prevention and Treatment of Cerebral Vasospasm after Subarachnoid Hemorrhage – a Randomized Placebo-Controlled Trial to assess Safety, Tolerability and Feasibility

Introduction: Dantrolene is neuroprotective in animal models and may attenuate cerebral vasospasm (cVSP) after aneurysmal subarachnoid hemorrhage (aSAH) in humans. We evaluated safety/tolerability and feasibility of intravenous dantrolene (IV-D) after aSAH. Methods: In this single-center, randomized, double blind, placebo-controlled trial, 31 patients with acute aSAH were randomized to IV-D 1.25 mg IV every 6 hours x 7 days (n=16) or placebo (n=15). Primary endpoint was incidence of hyponatremia (sNa ≤ 134 mmol/L) and liver toxicity (% patients with ALT, AST and AlkPhos \u3e5x upper limit of normal). Secondary safety endpoints included tolerability, systemic hypotension and intracranial hypertension. Efficacy was explored by clinical, transcranial Doppler (TCD) or angiographic cVSP occurrence, delayed cerebral ischemia (DCI) and 3-month modified-Rankin-Scale, Glasgow Outcome Scale and Barthel Index. Statistical analysis was performed using non-parametric tests, generalized estimating equations and mixed models. Results: Between IV-D vs. placebo, no differences were observed in the primary outcome (hyponatremia: 44% vs. 67% [p=0.29]; liver toxicity 6% vs. 0% [p=1.0]). Numerically more AEs and SAEs were seen in the IV-D group, but did not reach statistical significance (16 vs. 5 AEs, of which 5 vs. 2 were severe; RR 2.2; 95% CI 0.7-6.7; p=0.16). Three IV-D vs. two placebo patients reached stop criteria: one IV-D patient developed liver toxicity; two patients in each group developed brain edema requiring osmotherapy. No differences in angiographic, TCD, clinical cVSP, DCI, or 3-month functional outcomes were seen. Quantitative angiogram analysis revealed a trend towards increased vessel diameters in the IV-D group after the 7-day infusion-period (p=0.05). Conclusions: In this small trial, IV-Dantrolene after aSAH was feasible, tolerable and safe, but was underpowered to show efficacy or outcome differences

Routine activities and proactive police activity: a macro-scale analysis of police searches in London and New York City

This paper explored how city-level changes in routine activities were associated with changes in frequencies of police searches using six years of police records from the London Metropolitan Police Service and the New York City Police Department. Routine activities were operationalised through selecting events that potentially impacted on (a) the street population, (b) the frequency of crime or (c) the level of police activity. OLS regression results indicated that routine activity variables (e.g. day of the week, periods of high demand for police service) can explain a large proportion of the variance in search frequency throughout the year. A complex set of results emerged, revealing cross-national dissimilarities and the differential impact of certain activities (e.g. public holidays). Importantly, temporal frequencies in searches are not reducible to associations between searches and recorded street crime, nor changes in on-street population. Based on the routine activity approach, a theoretical police-action model is proposed

Dietary supplementation with New Zealand blackcurrant extract enhances fat oxidation during submaximal exercise in the heat

Objectives. This study investigated the effect of 7 days’ supplementation with New Zealand blackcurrant extract on thermoregulation and substrate metabolism during running in the heat. Design. Randomized, double-blind, cross-over study. Methods. Twelve men and six women (mean ± SD: Age 27 ± 6 years, height 1.76 ± 0.10 m, mass 74 ± 12 kg, V˙ O2max 53.4 ± 7.0 mL kg−1 min−1) completed one assessment of maximal aerobic capacity and one familiarisation trial (18 ◦C, 40% relative humidity, RH), before ingesting 2 × 300 mg day−1 capsules of CurraNZTM (each containing 105 mg anthocyanin) or a visually matched placebo (2 × 300 mg microcrystalline cellulose M102) for 7days (washout 14 days). On day 7 of each supplementation period, participants completed 60 min of fasted running at 65% V˙ O2max in hot ambient conditions (34 ◦C and 40% relative humidity). Results: Carbohydrate oxidation was decreased in the NZBC trial [by 0.24 g min−1 (95% CI: 0.21–0.27 g min-1)] compared to placebo (p = 0.014, d = 0.46), and fat oxidation was increased in the NZBC trial [by 0.12 g min−1 (95% CI: 0.10 to 0.15 g min−1)], compared to placebo (p = 0.008, d = 0.57). NZBC did not influence heart rate (p = 0.963), rectal temperature (p = 0.380), skin temperature (p = 0.955), body temperature (p = 0.214) or physiological strain index (p = 0.705) during exercise. Conclusions. Seven-days intake of 600 mg NZBC extract increased fat oxidation without influencing cardiorespiratory or thermoregulatory variables during prolonged moderate intensity running in hot conditions

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

New Zealand blackcurrant extract modulates the heat shock response in men during exercise in hot ambient conditions

Purpose: To determine if 7d of New Zealand blackcurrant (NZBC) extract alters the heat shock, inflammatory and apoptotic response during prolonged exertional-heat stress. Methods: Ten men (Age: 29 ± 2 years, Stature: 1.82 ± 0.02 m, Mass: 80.3 ± 2.7 kg, V̇O2max: 56 ± 2 mL·kg−1·min−1) ingested two capsules of CurraNZ™ (NZBC extract: 210 mg anthocyanins·day−1) or PLACEBO for 7d prior to 1 h treadmill run (65% V̇O2max) in hot ambient conditions (34 °C/40% RH). Blood samples were collected before (Pre), immediately after (Post), 1 h after (1-Post), and 4 h after (4-Post) exercise. Heat shock proteins (HSP90, HSP70, HSP32) were measured in plasma. HSP and protein markers of inflammatory capacity (TLR4, NF-κB) and apoptosis (BAX/BCL-2, Caspase 9) were measured in peripheral blood mononuclear cells (PBMC). Results: eHSP32 was elevated at baseline in NZBC(+ 31%; p < 0.001). In PLACEBO HSP32 content in PBMC was elevated at 4-Post(+ 98%; p = 0.002), whereas in NZBC it fell at Post(− 45%; p = 0.030) and 1-Post(− 48%; p = 0.026). eHSP70 was increased at Post in PLACEBO(+ 55.6%, p = 0.001) and NZBC (+ 50.7%, p = 0.010). eHSP90 was increased at Post(+ 77.9%, p < 0.001) and 1-Post(+ 73.2%, p < 0.001) in PLACEBO, with similar increases being shown in NZBC (+ 49.0%, p = 0.006 and + 66.2%, p = 0.001; respectively). TLR4 and NF-κB were both elevated in NZBC at PRE(+ 54%, p = 0.003 and + 57%, p = 0.004; respectively). Main effects of study condition were also shown for BAX/BCL-2(p = 0.025) and Caspase 9 (p = 0.043); both were higher in NZBC. Conclusion: 7d of NZBC extract supplementation increased eHSP32 and PBMC HSP32 content. It also increased inflammatory and apoptotic markers in PBMC, suggesting that NZBC supports the putative inflammatory response that accompanies exertional-heat stress