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Mastitis is one of the most prevalent and costly diseases in dairy cattle. Key components for adequate mastitis control are the detection of early stages of infection, as well as the selection of appropriate management interventions and therapies based on the causal pathogens associated with the infection. The objective was to characterize the pattern of electrical conductivity (EC) in milk during intramammary infection, considering specific mastitis-causing pathogen groups involvement. Cows (n = 200) identified by an in-line mastitis detection system with a positive deviation ≥15% in the manufacturer’s proprietary algorithm for EC (high electrical conductivity (HEC)) were considered cases and enrolled in the study at the subsequent milking. One control (CON) cow, within normal ranges for EC, was matched to each case. A composite milk sample was collected aseptically from each cow for bacteriological culture. Milk yield (MY) and EC were recorded for each milking during ±7 days relative to enrollment. Milk cultures were categorized into gram positive (GP), gram negative (GN), other (OTH) and no growth (NOG). Data were submitted for repeated-measures analysis with EC as the dependent variable and EC status at day −1, bacteriological culture category, parity number, stage of lactation and days relative to sampling as main independent variables. Average (± standard error (SE)) EC was greater in HEC than in CON cows (12.5 ± 0.5 v. 10.8 ± 0.5 mS/cm) on the day of identification (day −1). Milk yield on day −1 was greater in CON than in HEC (37.6 ± 5.1 v. 33.5 ± 5.2 kg). For practical management purposes, average EC on day −1 was similar for the different bacteriological culture categories: 11.4 ± 0.6, 11.7 ± 0.5, 12.3 ± 0.8 and 11.7 ± 0.5 mS/cm in GN, GP, OTH and NOG, respectively. Parity number was only associated with day −1 EC in HEC group, with the greatest EC values in parity 3 (12.3 ± 0.3 mS/cm), followed by parity 2 (11.9 ± 0.2 mS/cm), parity >3 (11.6 ± 0.5 mS/cm) and primiparous cows (11.2 ± 0.2 mS/cm). An effect on EC for the interaction of day relative to identification by pathogen gram category was observed. The same interaction effect was observed on daily MY. Overall, the level of variation for MY and EC between- and within-cows was substantial, and as indicated by the model diagnostic procedures, the magnitude of the variance in the cows in the CON group resulted in deviations from normality in the residuals. We concluded that characteristic temporal patterns in EC and MY in particular pathogen groups may provide indications for differentiation of groups of mastitis-causing pathogens. Further research to build detection models including EC, MY and cow-level factors is required for accurate differentiation.
Increasing fluorination of organosilyl nitrile solvents improves ionic conductivities of lithium salt electrolytes, resulting from higher values of salt dissociation. Ionic conductivities at 298 K range from 1.5 to 3.2 mS/cm for LiPF6 salt concentrations at 0.6 or 0.7 M. The authors also report on solvent blend electrolytes where the fluoroorganosilyl (FOS) nitrile solvent is mixed with ethylene carbonate and diethyl carbonate. Ionic conductivities of the FOS solvent/carbonate blend electrolytes increase achieving ionic conductivities at 298 K of 5.5–6.3 mS/cm and salt dissociation values ranging from 0.42 to 0.45. Salt dissociation generally decreases with increasing temperature.
The authors report on 7Li, 19F, and 1H pulsed field gradient NMR measurements of 26 organosilyl nitrile solvent-based electrolytes of either lithium bis(trifluorosulfonyl)imide (LiTFSI) or lithium hexafluorophosphate. Lithium transport numbers (as high as 0.50) were measured and are highest in the LiTFSI electrolytes. The authors also report on solvent blend electrolytes of fluoroorganosilyl (FOS) nitrile solvent mixed with ethylene carbonate (EC) and diethyl carbonate. Solvent diffusion measurements on an electrolyte with 6% FOS suggest both the FOS and EC solvate the lithium cation. By comparing lithium transport and transference numbers, the authors find less ion pairing in FOS nitrile carbonate blend electrolytes and difluoroorganosilyl nitrile electrolytes.
First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
Before weaning, breast milk is the physiological form of neonatal nutrition, providing pups with all nutrient requirements. Maternal low-protein diet (LPD) during pregnancy and lactation induces adverse changes in key maternal organs, which have negative effects on pup development. We studied the effects of maternal LPD on liver weight, mammary gland (MG) cell differentiation, milk composition and production and pup development throughout lactation. We fed rats with control (C) or LPD (R) during pregnancy and lactation. At 7 d early, 14 d mid and 21 d late lactation stages, maternal biochemical parameters, body, liver and MG weights were analysed. MG cell differentiation was analysed by haematoxylin and eosin staining; milk nutrient composition and production were studied; pup body, liver and brain weights, hippocampal arachidonic acid (AA) and DHA were quantified. Results showed lower body and liver weights, minor MG cell differentiation and lower serum insulin and TAG in R compared with C. R milk contained less protein and higher AA at early and mid stages compared with C. R pup milk and fat intake were lower at all stages. R protein intake at early and mid stages and DHA intake at mid and late stages were lower compared with C. In R pups, lower body, liver and brain weights were associated with decreased hippocampal AA and DHA. We conclude that maternal LPD impairs liver and MG function and induces significant changes in maternal milk composition, pup milk intake and organ development.
Background: SMA1 is a neurodegenerative disease caused by bi-allelic survival motor neuron 1 gene (SMN1) deletion/mutation. In the phase 1 study, SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of symptomatic SMA1 patients. We report preliminary data of STR1VE, a pivotal study (NCT03306277) evaluating efficacy and safety of a one-time intravenous AVXS-101 infusion. Methods: STR1VE is a phase 3, multicenter, open-label, single-arm study in SMA1 patients aged <6 months (bi-allelic SMN1 loss, 2xSMN2). Primary outcomes: independent sitting for ≥30 seconds (18 months) and survival (14 months). Secondary outcomes: ability to thrive and ventilatory support (18 months). Exploratory outcomes: CHOP-INTEND and Bayley Scales of Infant and Toddler Development scores. Results: Enrollment is complete with 22 patients dosed. Mean age at symptom onset, genetic diagnosis, and enrollment was 1.9 (0–4.0), 2.1 (0.5–4.0), and 3.7 (0.5–5.9) months. At baseline, no patient required ventilatory/nutritional support, and all exclusively fed by mouth. Mean baseline CHOP-INTEND score was 32.6 (17.0–52.0), which increased 6.9 (-4.0–16.0, n=20), 10.4 (2.0–18.0, n=12), and 11.6 (-3.0–23.0, n=9) points at 1, 2, and 3 months; updates provided at congress. Conclusions: Preliminary data from STR1VE show rapid motor function improvements in SMA1 patients, paralleling phase 1 findings.
The new species Lenonchium zanjanense sp. n. is described from a natural habitat of Zanjan province, Iran, including line, light microscopy and scanning electron microscopy illustrations and a molecular (18S, 28S) study. It is characterized by its 3.50–4.51 mm long body, rounded lip region, continuous and 13.5–15.5 µm broad, odontostyle 21–24 µm long, neck 362–490 µm long, double guiding ring, pharyngeal expansion 190–285 µm long, female genital system didelphic–amphidelphic, uterus simple and 185–320 µm long or 3.4–5.9 times the corresponding body diameter, vulva nearly equatorial (V = 45–53), tail conical-elongated to filiform (90–165 µm, c = 23–43, c′ = 2.4–5.3) with three or four mucro-like projections at the tip, spicules 58–64 µm long and 16–21 contiguous ventromedian supplements ending at the level of the anterior end of the spicules. The taxonomy of the genus is updated, with an emended diagnosis, list of species, key to their identification and a compendium of their main morphometrics. Lenonchium asterocaudatum is regarded as identical and a junior synonym of L. denticaudatum. New insights into the phylogeny of the group are also provided, and the classification of Lenonchium within Nordiidae is seriously questioned.
An essential strategy to increase coverage of psychosocial treatments globally is task shifting to non-medical counsellors, but evidence on its effectiveness is still scarce. This study evaluates the effectiveness of lay psychosocial counselling among persons with psychological distress in a primary health care setting in rural Nepal.
A parallel randomized controlled trial in Dang, rural Nepal (NCT03544450). Persons aged 16 and older attending primary care and with a General Health Questionnaire (GHQ-12) score of 6 or more were randomized (1:1) to receive either non-medical psychosocial counselling (PSY) or enhanced usual care (EUC). PSY was provided by lay persons with a 6-month training and consisted of 5-weekly counselling sessions of 35–60 min with a culturally adapted solution-focused approach. EUC was provided by trained primary health workers. Participants were followed up at 1 (T1) and 6 months (T2). The primary outcome, response to treatment, was the reduction of minimum 50% in the Beck Depression Inventory (BDI) score.
A total of 141 participants, predominantly socially disadvantaged women, were randomized to receive PSY and 146 to EUC. In the PSY, 123 participants and 134 in the EUC were analysed. In PSY, 101 participants (81.4%) had a response compared with 57 participants (42.5%) in EUC [percentage difference 39.4% (95% CI 28.4–50.4)]. The difference in BDI scores at T2 between PSY and EUC was −7.43 (95% CI −9.71 to −5.14).
Non-medical (lay) psychosocial counselling appears effective in reducing depressive symptoms, and its inclusion in mental health care should be considered in low-resource settings.
The present study investigated the adsorption of fluorides in natural zeolites clinoptilolite-type, sourced in Sonora, Mexico, and modified with Fe. Characterization of the material was carried out along with determination of kinetic parameters varying time and concentration of reagents to calculate maximum adsorption capacity. To determine thermodynamic parameters temperature was varied for accurate characterization of the adsorption process. It was found that the zeolite fixed Fe in its structure without model significant modification, likewise when put in contact with a fluoride solution (F-), it was capable of taking up these ions through adsorption due to the interaction between the sorbato and the pollutant. The kinetics best fit Pseudo-second-order model with Qmax=0.91 mgg-1, therefore it indicates that the process is reversible, spontaneous and endothermic what can favor the reuse of the material.
This work reports by the first time a method to control the geometry of Ga2O3 films nanocrystallites at 350 °C. The formation of controlled shaped nano-crystallites of γ-Ga2O3 from amorphous Ga2O3 films grown by RF-Sputtering at room temperature driven by nano-layers of group IB metals (Cu, Ag or Au) is studied. The reported results can be explained by the role of subsurface metal nano-layers and the non-equilibrium nature of the sputtering processes. To study the effects on the surface structure and their optical properties arrays of amorphous-Ga2O3/IB-metal/amorphous-Ga2O3 were annealed in dry N2 atmosphere at 350 °C by 50, 100 and 150 min. The experimental results can be explained by the evolution of the amorphous character of the films amorphous films towards the nanocrystalline γ-Ga2O3 phase driven by the metal nano-layer seed nature. As the annealing time was increased the transition from amorphous-Ga2O3 to the nanocrystalline γ-Ga2O3 phase was detected by X-ray diffraction analysis. The transition to the nanocrystalline γ-Ga2O3 is demonstrated by the formation of octahedral, triangle and ball shape nanocrystallites with sizes of ∼5 to 50 nm according to FE-SEM analysis. The influence of the metal nano-layer is clearly seen by the shift of the plasmon frequency resonance produced by the Ga2O3/IB-metal/Ga2O3 arrays in the region from 400 to 600 nm caused by the modification of the interface Ga2O3/IB-metal produced by the applied annealing stages.
We describe the use of immobilized deoxyribonucleic acid (DNA) in a silica matrix as a biorecognition agent for the detection of albendazole sulfoxide (ASU), the primary metabolite of albendazole and a suspected teratogenic and embryotoxic agent. The biomaterial (DNA-containing gel) was synthesized by physical entrapment of salmon sperm in an inorganic silicate matrix by the sol-gel method. Functionality of the DNA-containing gel was evaluated by comparative offline frontal chromatography followed by HPLC analysis of ASU and caffeine (CAF, control) using DNA-containing gel and DNA-free gel. The DNA-containing gel showed relatively high specific retention for ASU, while CAF showed no retention using frontal analysis. We anticipate that the DNA-containing gel can be implemented to identify the interactions of DNA with other active pharmaceutical ingredients (APIs) and their metabolites in a readily available, sensitive and selective frontal chromatography experiment.
A novel process for Boron doping of ultrananocrystalline diamond (UNCD) films, using thermal diffusion, is described. Hall measurements show an increase in carrier concentration from 1013 to 1020 cm−3. Ultraviolet Photoelectron Spectroscopy and x-ray Photoelectron Spectroscopy show a band gap of 4.4 eV, a work function of 5.1 eV and a Fermi level at 2.0 eV above the valence band. Boron atoms distribution through UNCD films, was measured by Secondary Ion Mass Spectrometry, revealing Boron atoms diffusivity of about 10−14 cm2/s. Raman spectroscopy and x-ray Diffraction analysis revealed that UNCD films did not suffer graphitization nor structural damage during annealing.
Current standard-of-care for glioblastoma (GBM) includes surgery, radiation and temozolomide. Most tumors recur within a year from diagnosis and median survival for recurrent GBM (rGBM) is 3-9 months. Unmethylated promoter status for O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for temozolomide-resistance, exhibited by most GBM patients. VAL-083 is a DNA-targeting agent with a mechanism-of-action that is independent of MGMT. VAL-083 overcomes temozolomide-resistance in GBM cell-lines, cancer stem cells, and in vivo models. VAL-083 readily crosses the blood-brain barrier and accumulates in brain-tumor tissue. We recently completed a VAL-083 dose-escalation trial in temozolomide- and bevacizumab-refractory rGBM and determined that 40mg/m2/day given intravenously on days 1,2,3 of a 21-day cycle is generally well-tolerated. This dosing regimen was selected for subsequent GBM trials, including an ongoing single-arm, biomarker-driven Phase 2 trial (N=48) in temolozomide-refractory, bevacizumab-naïve rGBM , MGMT-unmethylated (Clinicaltrials.gov:NCT02717962). The primary objective of this study is to determine if VAL-083 improves OS compared to a historical control of 7.15 months for MGMT-unmethylated rGBM patients treated with lomustine (EORTC26101). In addition, another single-arm, biomarker-driven, Phase 2 study (N=25) of VAL-083 in combination with radiotherapy in newly diagnosed GBM, MGMT-unmethylated is ongoing (Clinicaltrials.gov:NCT03050736). This trial aims to determine a dose for further study of VAL-083 in combination with radiotherapy and explore if VAL-083 improves PFS and OS compared to historical results in newly diagnosed GBM. Enrollment and safety data updates will be provided at the meeting. The results of these studies, if successful, may support VAL-083 as part of a new chemotherapeutic treatment paradigm for GBM.
To compare the epidemiology, clinical characteristics, and mortality of patients with bloodstream infections (BSI) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) versus ESBL-producing Klebsiella pneumoniae (ESBL-KP) and to examine the differences in clinical characteristics and outcome between BSIs caused by isolates with CTX-M versus other ESBL genotypes
As part of the INCREMENT project, 33 tertiary hospitals in 12 countries retrospectively collected data on adult patients diagnosed with ESBL-EC BSI or ESBL-KP BSI between 2004 and 2013. Risk factors for ESBL-EC versus ESBL-KP BSI and for 30-day mortality were examined by bivariate analysis followed by multivariable logistic regression.
The study included 909 patients: 687 with ESBL-EC BSI and 222 with ESBL-KP BSI. ESBL genotype by polymerase chain reaction amplification of 286 isolates was available. ESBL-KP BSI was associated with intensive care unit admission, cardiovascular and neurological comorbidities, length of stay to bacteremia >14 days from admission, and a nonurinary source. Overall, 30-day mortality was significantly higher in patients with ESBL-KP BSI than ESBL-EC BSI (33.7% vs 17.4%; odds ratio, 1.64; P=.016). CTX-M was the most prevalent ESBL subtype identified (218 of 286 polymerase chain reaction-tested isolates, 76%). No differences in clinical characteristics or in mortality between CTX-M and non–CTX-M ESBLs were detected.
Clinical characteristics and risk of mortality differ significantly between ESBL-EC and ESBL-KP BSI. Therefore, all ESBL-producing Enterobacteriaceae should not be considered a homogeneous group. No differences in outcomes between genotypes were detected.
Isotopic composition of leaf carbon (δ13C) and nitrogen (δ15N) is determined by biotic and abiotic factors. In order to determine the influence of leaf habit and site on leaf δ13C and δ15N in the understorey of two Atlantic forests in Brazil that differ in annual precipitation (1200 and 1900 mm), we measured these isotopes in the shaded understorey of 38 tropical tree species (20 in the 1200-mm site and 18 in the 1900-mm site). Mean site values for δ15N were significantly lower at the 1200-mm site (−1.4‰) compared with the 1900-mm site (+3.0‰), and δ13C was significantly greater in the 1200-mm site (−30.4‰) than in the 1900-mm site (−31.6‰). Leaf C concentration was greater and leaf N concentration was lower at 1200-mm than at 1900-mm. Leaf δ15N was negatively correlated with δ13C across the two sites. Leaf δ13C and δ15N of evergreen and deciduous species were not significantly different within a site. No significant phylogenetic signal for any traits among the study species was found. Overall, site differences were the main factor distinguishing traits among species, suggesting strong functional convergence to local climate and soils within each site for individuals in the shaded understorey.
A new species belonging to the genus Belondira is described from natural areas in Iran. Belondira coomansi n. sp. is characterized by its general size, the dimensions and appearance of its lip region, presence of distinct labial and post-labial sclerotization, the length of the odontostyle and its inconspicuous lumen and aperture, the length of the neck and its pharyngeal expansion, the reduction of the female anterior genital branch to a simple uterine sac, a very short posterior uterus, the anterior position of the vulva, the length and shape of the caudal region with distinctly thick cuticle at its tip, the length of the spicules, and the presence of only one pair of ventromedian supplements. The new species is close to Belondira brevibulba, B. sacchari, B. tenuidens and B. thornei, and it is compared to them. Molecular characterization (D2–D3 expansion segments of the rRNA large subunit) of the new species is also provided, representing only the second species of this genus for which any DNA sequence data are available.
A new genus and new species, Tarantobelus arachnicida, was found in the oral opening of tarantula spiders bred in captivity in Poland. The new species is characterized by having a small body (0.77–0.95 mm long in females and 0.66–0.84 mm in males), cuticle poorly annulated by transverse incisures, lateral field inconspicuous, lips separated with small cuticular flaps topping each lip, stoma panagrolaimoid with gymnostom well developed with robust and refringent rhabdia, pharynx panagrolaimoid with isthmus slightly longer than the basal bulb, intestine with cardiac (anterior) and rectal (posterior) areas with narrower walls. Mature females with intestinal cells including needle crystal packs, excretory pore at isthmus level, female reproductive system panagrolaimoid with post-vulval sac 0.4–0.8 times the length of the corresponding body diameter and having very thick walls, vulva very prominent, female rectum 0.8–1.3 times the length of the anal body diameter, female tail conical with acute tip with phasmids at 58–62% of its length. Male tail conical with long and thin mucro, spicules ventrad bent having rounded manubrium and thick gubernaculum. Description, measurements and illustrations of the new species are provided. Molecular analyses show its relationship with Brevibucca and Cuticonema. On the other hand, Medibulla and its corresponding subfamily Medibullinae, previously in Osstellidae, are transferred to Panagrolaimidae, being Shahnematinae, the junior synonym of Medibullinae. Indocephalobus, recently proposed and located in the family Panagrolaimidae, is considered a junior synonym of Diplogastrellus (Diplogasteromorpha), and its only species, I. zebrae, is considered a junior synonym of D. gracilis. In addition, a key to identification of panagrolaimoid genera is included.