Leech blood-meal invertebrate-derived DNA reveals differences in Bornean mammal diversity across habitats

The application of metabarcoding to environmental and invertebrate-derived DNA (eDNA and iDNA) is a new and increasingly applied method for monitoring biodiversity across a diverse range of habitats. This approach is particularly promising for sampling in the biodiverse humid tropics, where rapid land-use change for agriculture means there is a growing need to understand the conservation value of the remaining mosaic and degraded landscapes. Here we use iDNA from blood-feeding leeches (Haemadipsa picta) to assess differences in mammalian diversity across a gradient of forest degradation in Sabah, Malaysian Borneo. We screened 557 individual leeches for mammal DNA by targeting fragments of the 16S rRNA gene and detected 14 mammalian genera. We recorded lower mammal diversity in the most heavily degraded forest compared to higher quality twice logged forest. Although the accumulation curves of diversity estimates were comparable across these habitat types, diversity was higher in twice logged forest, with more taxa of conservation concern. In addition, our analysis revealed differences between the community recorded in the heavily logged forest and that of the twice logged forest. By revealing differences in mammal diversity across a human-modified tropical landscape, our study demonstrates the value of iDNA as a noninvasive biomonitoring approach in conservation assessments. © 2020 The Authors. Molecular Ecology published by John Wiley & Sons Lt

Influence of storm surge on tidal range energy

The regular and predictable nature of the tide makes the generation of electricity with a tidal lagoon or barrage an attractive form of renewable energy, yet storm surges affect the total water-level. Here, we present the first assessment of the potential impact of storm surges on tidal-range power. Water-level data (2000–2012) at nine UK tide gauges, where tidal-range energy is suitable for development (e.g. Bristol Channel), was used to predict power. Storm surge affected annual resource estimates −5% to +3%, due to inter-annual variability, which is lower than other sources of uncertainty (e.g. lagoon design); therefore, annual resource estimation from astronomical tides alone appears sufficient. However, instantaneous power output was often significantly affected (Normalised Root Mean Squared Error: 3%–8%, Scatter Index: 15%–41%) and so a storm surge prediction system may be required for any future electricity generation scenario that includes large amounts of tidal-range generation. The storm surge influence to tidal-range power varied with the electricity generation strategy considered (flooding tide only, ebb-only or dual; both flood and ebb), but with some spatial and temporal variability. The flood-only strategy was most affected by storm surge, mostly likely because tide-surge interaction increases the chance of higher water-levels on the flooding tide

Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study.

BACKGROUND: Outcome of low-grade glioma (WHO grade II) is highly variable, reflecting molecular heterogeneity of the disease. We compared two different, single-modality treatment strategies of standard radiotherapy versus primary temozolomide chemotherapy in patients with low-grade glioma, and assessed progression-free survival outcomes and identified predictive molecular factors. METHODS: For this randomised, open-label, phase 3 intergroup study (EORTC 22033-26033), undertaken in 78 clinical centres in 19 countries, we included patients aged 18 years or older who had a low-grade (WHO grade II) glioma (astrocytoma, oligoastrocytoma, or oligodendroglioma) with at least one high-risk feature (aged >40 years, progressive disease, tumour size >5 cm, tumour crossing the midline, or neurological symptoms), and without known HIV infection, chronic hepatitis B or C virus infection, or any condition that could interfere with oral drug administration. Eligible patients were randomly assigned (1:1) to receive either conformal radiotherapy (up to 50·4 Gy; 28 doses of 1·8 Gy once daily, 5 days per week for up to 6·5 weeks) or dose-dense oral temozolomide (75 mg/m(2) once daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles). Random treatment allocation was done online by a minimisation technique with prospective stratification by institution, 1p deletion (absent vs present vs undetermined), contrast enhancement (yes vs no), age (<40 vs ≥40 years), and WHO performance status (0 vs ≥1). Patients, treating physicians, and researchers were aware of the assigned intervention. A planned analysis was done after 216 progression events occurred. Our primary clinical endpoint was progression-free survival, analysed by intention-to-treat; secondary outcomes were overall survival, adverse events, neurocognitive function (will be reported separately), health-related quality of life and neurological function (reported separately), and correlative analyses of progression-free survival by molecular markers (1p/19q co-deletion, MGMT promoter methylation status, and IDH1/IDH2 mutations). This trial is closed to accrual but continuing for follow-up, and is registered at the European Trials Registry, EudraCT 2004-002714-11, and at ClinicalTrials.gov, NCT00182819. FINDINGS: Between Sept 23, 2005, and March 26, 2010, 707 patients were registered for the study. Between Dec 6, 2005, and Dec 21, 2012, we randomly assigned 477 patients to receive either radiotherapy (n=240) or temozolomide chemotherapy (n=237). At a median follow-up of 48 months (IQR 31-56), median progression-free survival was 39 months (95% CI 35-44) in the temozolomide group and 46 months (40-56) in the radiotherapy group (unadjusted hazard ratio [HR] 1·16, 95% CI 0·9-1·5, p=0·22). Median overall survival has not been reached. Exploratory analyses in 318 molecularly-defined patients confirmed the significantly different prognosis for progression-free survival in the three recently defined molecular low-grade glioma subgroups (IDHmt, with or without 1p/19q co-deletion [IDHmt/codel], or IDH wild type [IDHwt]; p=0·013). Patients with IDHmt/non-codel tumours treated with radiotherapy had a longer progression-free survival than those treated with temozolomide (HR 1·86 [95% CI 1·21-2·87], log-rank p=0·0043), whereas there were no significant treatment-dependent differences in progression-free survival for patients with IDHmt/codel and IDHwt tumours. Grade 3-4 haematological adverse events occurred in 32 (14%) of 236 patients treated with temozolomide and in one (<1%) of 228 patients treated with radiotherapy, and grade 3-4 infections occurred in eight (3%) of 236 patients treated with temozolomide and in two (1%) of 228 patients treated with radiotherapy. Moderate to severe fatigue was recorded in eight (3%) patients in the radiotherapy group (grade 2) and 16 (7%) in the temozolomide group. 119 (25%) of all 477 patients had died at database lock. Four patients died due to treatment-related causes: two in the temozolomide group and two in the radiotherapy group. INTERPRETATION: Overall, there was no significant difference in progression-free survival in patients with low-grade glioma when treated with either radiotherapy alone or temozolomide chemotherapy alone. Further data maturation is needed for overall survival analyses and evaluation of the full predictive effects of different molecular subtypes for future individualised treatment choices. FUNDING: Merck Sharpe & Dohme-Merck & Co, Canadian Cancer Society, Swiss Cancer League, UK National Institutes of Health, Australian National Health and Medical Research Council, US National Cancer Institute, European Organisation for Research and Treatment of Cancer Cancer Research Fund

POD Analysis of Cavity Flow Instability

A Mach 1.5 turbulent cavity flow develops large-amplitude oscillations, pressure drag and noise. This type of flow instability affects practical engineering applications, such as aircraft store bays. A simple model of the flow instability is sought towards developing a real-time model-based active control system for simple geometries, representative of open aircraft store bays. An explicit time marching second-order accurate finite-volume scheme has been used to generate time-dependent benchmark cavity flow data. Then, a simpler and leaner numerical predictor for the unsteady cavity pressure was developed, based on a Proper Orthogonal Decomposition of the benchmark data. The low order predictor gives pressure oscillations in good agreement with the benchmark CFD method. This result highlights the importance of large-scale phase-coherent structures in the Mach 1.5 turbulent cavity flow. At the selected test conditions, the significant pressure ‘energy’ content of these structures enabled an effective reduced order model of the cavity dynamic system. Directions and methods to further streamline and simplify the unsteady pressure predictor have been highlighted

Hair Follicle Apoptosis and Bcl-2

Hair follicle (HF) morphogenesis and cycling are characterized by a tightly controlled balance of proliferation, differentiation and apoptosis. The members of the bcl-2 family of proto-oncogenes are important key players in the apoptosis control machinery of most cell types. Bcl-2, an apoptosis inhibitor, and Bax, an apoptosis promoter, show tightly regulated, hair cycle-dependent expression patterns: during catagen, the distal ORS of the HF remains strongly positive for Bcl-2 and Bax; in contrast, the proximal epithelial part of the HF loses most Bcl-2 expression while it remains strongly positive for Bax. In Bcl-2 null mice, skin becomes markedly hypopigmented during the first postnatal anagen probably due to increased melanocyte apoptosis. Reportedly, these mice also show a retardation of the first anagen development after birth. Transgenic mice overexpressing Bcl-2 under the control of the keratin-1 promoter display multifocal epidermal hyperplasia and aberrant expression of keratin-6, while alterations of HF cycling have not been investigated. Surprisingly, Bcl-2 overexpression under the control of the keratin-14 promoter leads to accelerated catagen progression and increased chemotherapy-induced apoptosis, HF dystrophy and alopecia. Transgenic mice overexpressing Bcl-X(L), another anti-apoptotic bcl-2 family member, under the control of the K14 promoter, reportedly also display accelerated catagen development. These and other Bcl-2 transgenic and null mice are now available to further dissect the as yet unclear, and likely complex, role of Bcl-2 in HF growth and pigmentation

Slowed muscle oxygen uptake kinetics with raised metabolism are not dependent on blood flow or recruitment dynamics

Oxygen uptake kinetics (τ[Image: see text]) are slowed when exercise is initiated from a raised metabolic rate. Whether this reflects the recruitment of muscle fibres differing in oxidative capacity, or slowed blood flow ([Image: see text]) kinetics is unclear. This study determined τ[Image: see text] in canine muscle in situ, with experimental control over muscle activation and [Image: see text] during contractions initiated from rest and a raised metabolic rate. The gastrocnemius complex of nine anaesthetised, ventilated dogs was isolated and attached to a force transducer. Isometric tetanic contractions (50 Hz; 200 ms duration) via supramaximal sciatic nerve stimulation were used to manipulate metabolic rate: 3 min stimulation at 0.33 Hz (S1), followed by 3 min at 0.67 Hz (S2). Circulation was initially intact (SPON), and subsequently isolated for pump-perfusion (PUMP) above the greatest value in SPON. Muscle [Image: see text] was determined contraction-by-contraction using an ultrasonic flowmeter and venous oximeter, and normalised to tension-time integral (TTI). τ[Image: see text]/TTI and τ[Image: see text] were less in S1(SPON) (mean ± s.d.: 13 ± 3 s and 12 ± 4 s, respectively) than in S2(SPON) (29 ± 19 s and 31 ± 13 s, respectively; P < 0.05). τ[Image: see text]/TTI was unchanged by pump-perfusion (S1(PUMP), 12 ± 4 s; S2(PUMP), 24 ± 6 s; P < 0.001) despite increased O(2) delivery; at S2 onset, venous O(2) saturation was 21 ± 4% and 65 ± 5% in SPON and PUMP, respectively. [Image: see text] kinetics remained slowed when contractions were initiated from a raised metabolic rate despite uniform muscle stimulation and increased O(2) delivery. The intracellular mechanism may relate to a falling energy state, approaching saturating ADP concentration, and/or slowed mitochondrial activation; but further study is required. These data add to the evidence that muscle [Image: see text] control is more complex than previously suggested