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The microbiome profoundly influences many traits in medically relevant vectors such as mosquitoes, and a greater functional understanding of host-microbe interactions may be exploited for novel microbial-based approaches to control mosquito-borne disease. Here, we characterized two CRISPR-Cas systems in a novel bacterium,SerratiaSp. Ag1, that was isolated from the gut of anAnopheles gambiaemosquito. Two distinct CRISPR-Cas systems were identified inSerratiaAg1, CRISPR1 and CRISPR2. Based oncasgene composition, CRISPR1 is classified as a Type I-E CRISPR-Cas system and has a single array, CRISPR1. CRISPR2 is a Type I-F system with two arrays, CRISPR2.1 and CRISPR2.2. RT-PCR analyses show that allcasgenes from both systems are expressed during logarithmic growth in culture media. The direct repeat sequence of CRISPRs 2.1 and 2.2 are identical and found in the arrays of otherSerratiaspp, includingS. marcescensandS. fonticola, whereas CRISPR1 was not. We searched for potential spacer targets and revealed an interesting difference between the two systems: only 9% of CRISPR1 (Type I-E) targets are in phage sequences and 91% are in plasmid sequences. Conversely, ~66% of CRISPR2 (Type I-F), targets are found within phage genomes. Our results highlight the presence of CRISPR loci in gut-associated bacteria of mosquitoes and indicate interplay between symbionts and invasive mobile genetic elements over evolutionary time.Data SummaryThere is no supporting external data generated for this work.

Introduction: Neoadjuvant chemotherapy (NACT) is becoming standard of care for presurgical treatment of triple negative breast cancer (TNBC) patients. Achievement of pathological complete response (pCR) after NACT is associated with improved outcomes. There is currently an unmet need in development of imaging and clinical tools for prediction of pCR to NACT in TNBC. We investigated use of deep learning convolution neural networks (CNNs) for early prediction of pCR in a TNBC cohort on the basis of MRI acquired before the initiation and at the midpoint, after completion of four cycles of NACT (C4). Materials and Methods: Baseline and C4 MRIs of 112 TNBC patients were collected from an ongoing prospective clinical trial (NCT02276443). Four patients were excluded because they underwent different treatment for the second regimen. Among the 108 patients, 52 patients (48%) had pCR confirmed at surgery. Positive enhancement integral (PEI) derived from the early phases of DCE MRI, and apparent diffusion coefficients (ADC) derived from DWI MRI (b = 100 and 800 s/mm2), were used for our investigation. The images were aligned and the tumor regions were cropped from all images. All tumor patches were normalized between [0, 1], and were padded to form matrices of the same size of 192×192×64 for PEI, or the size of 192×192×16 for ADC. The CNN was constructed using stacked 3D convolution and MaxPooling layers. It consisted of up to four channels for the inputs (baseline and C4 PEI and ADC). Features extracted from each channel were concatenated and regressed for pCR prediction via three densely connected layers. Binary cross-entropy was used as the loss function for CNN training, and the loss was optimized using an Adam optimizer with the initial learning rate of 0.0001. Because of the currently limited sample size, four-fold cross-validation was used for CNN training and evaluation. The patients were divided into four groups, each group had 27 patients and the pCR:non-pCR ratio was controlled as 13:14. For each fold, one group was reserved as the independent testing group, and the other three groups were combined for network training and internal validation. Receiver operating characteristic (ROC) curve was plotted for each fold of testing, and area under the curve (AUC) was calculated. Final performance of the CNN was determined by averaging the AUCs of the four testing folds. Additionally, to test the prediction efficacy of each input, we trained the CNN under the same settings but used PEI or ADC only as input, and the results were compared. Results: The CNN trained with PEI only achieved an average AUC of 0.65 ± 0.09. The second CNN trained with ADC only achieved an average AUC of 0.72 ± 0.07. The third CNN trained with both PEI and ADC achieved an average AUC of 0.73 ± 0.06. Conclusion and Discussion: Using baseline and mid-treatment MRIs, deep learning CNN showed promising performance to predict pCR in the early course of NACT. The prediction AUC for the independent testing groups was largely improved by using ADC to train the network, indicating that ADC can have more critical information than PEI in assisting pCR prediction during the early course of NACT. Future work includes curation of a larger patient data for network training and evaluation to improve the prediction performance and further validate generalization of the network. We will also explore more advanced network structures, through which the prediction performance can be improved. Four-fold cross-validation AUCs of the network using different data as inputs.PEIADCPEI+ADCFold 10.570.640.66Fold 20.760.800.77Fold 30.660.700.68Fold 40.590.740.79Average0.65 ± 0.090.72 ± 0.070.73 ± 0.06 Citation Format: Zijian Zhou, Nabil A Elshafeey, David E Rauch, Beatriz E Adrada, Rosalind P Candelaria, Mary S Guirguis, Wei Yang, Medine Boge, Rania M Mohamed, Gary J Whitman, Deanna L Lane, Huong C Le-Petross, Jessica WT Leung, Lumarie Santiago, Marion E Scoggins, David A Spak, Miral M Patel, Frances Perez, Debu Tripathy, Vicente Valero, Clinton Yam, Stacy Moulder, Jason B White, Jong Bum Son, Mark D Pagel, Jingfei Ma. Deep learning for early prediction of neoadjuvant chemotherapy response in triple negative breast cancers [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-03.

IntroductionA systematic literature search was undertaken to assess the impact of pre-, pro-, and syn-biotic supplementation on measures of gastrointestinal status at rest and in response to acute exercise.MethodsSix databases (Ovid MEDLINE, EMBASE, Cinahl, SportsDISCUS, Web of Science, and Scopus) were used. Included were human research studies in healthy sedentary adults, and healthy active adults, involving supplementation and control or placebo groups. Sedentary individuals with non-communicable disease risk or established gastrointestinal inflammatory or functional diseases/disorders were excluded.ResultsA total of n = 1,204 participants were included from n = 37 papers reported resting outcomes, and n = 13 reported exercise-induced gastrointestinal syndrome (EIGS) outcomes. No supplement improved gastrointestinal permeability or gastrointestinal symptoms (GIS), and systemic endotoxemia at rest. Only modest positive changes in inflammatory cytokine profiles were observed in n = 3/15 studies at rest. Prebiotic studies (n = 4/5) reported significantly increased resting fecal Bifidobacteria, but no consistent differences in other microbes. Probiotic studies (n = 4/9) increased the supplemented bacterial species-strain. Only arabinoxylan oligosaccharide supplementation increased total fecal short chain fatty acid (SCFA) and butyrate concentrations. In response to exercise, probiotics did not substantially influence epithelial injury and permeability, systemic endotoxin profile, or GIS. Two studies reported reduced systemic inflammatory cytokine responses to exercise. Probiotic supplementation did not substantially influence GIS during exercise.DiscussionSynbiotic outcomes resembled probiotics, likely due to the minimal dose of prebiotic included. Methodological issues and high risk of bias were identified in several studies, using the Cochrane Risk of Bias Assessment Tool. A major limitation in the majority of included studies was the lack of a comprehensive approach of well-validated biomarkers specific to gastrointestinal outcomes and many included studies featured small sample sizes. Prebiotic supplementation can influence gut microbial composition and SCFA concentration; whereas probiotics increase the supplemented species-strain, with minimal effect on SCFA, and no effect on any other gastrointestinal status marker at rest. Probiotic and synbiotic supplementation does not substantially reduce epithelial injury and permeability, systemic endotoxin and inflammatory cytokine profiles, or GIS in response to acute exercise.

The objective of this study was to evaluate different analytical methods of assessing failure of passive transfer (FPT) in neonatal calves. We hypothesized that 3 different media (i.e., centrifuged serum, centrifuged plasma, filtered plasma) and different analytical methods [i.e., ELISA, capillary electrophoresis (CE), Brix refractometer, and handheld optical refractometer] would be highly correlated with the gold standard radial immunodiffusion (RID) and would generate comparable results. Serum and plasma blood samples were collected from Holstein Friesian calves (n = 216) aged 1 to 7 d, from 2 commercial dairy herds in northeast Germany. The RID analysis showed that 59 of 216 calves (27%) had serum IgG concentrations of

Using metadata from previously published research, this investigation sought to explore: (1) whole-body total carbohydrate and fat oxidation rates of endurance (e.g., half and full marathon) and ultra-endurance runners during an incremental exercise test to volitional exhaustion and steady-state exercise while consuming a mixed macronutrient diet and consuming carbohydrate during steady-state running and (2) feeding tolerance and glucose availability while consuming different carbohydrate regimes during steady-state running. Competitively trained male endurance and ultra-endurance runners (n = 28) consuming a balanced macronutrient diet (57 ± 6% carbohydrate, 21 ± 16% protein, and 22 ± 9% fat) performed an incremental exercise test to exhaustion and one of three 3 h steady-state running protocols involving a carbohydrate feeding regime (76–90 g/h). Indirect calorimetry was used to determine maximum fat oxidation (MFO) in the incremental exercise and carbohydrate and fat oxidation rates during steady-state running. Gastrointestinal symptoms (GIS), breath hydrogen (H2), and blood glucose responses were measured throughout the steady-state running protocols. Despite high variability between participants, high rates of MFO [mean (range): 0.66 (0.22–1.89) g/min], Fatmax [63 (40–94) % V̇O2max], and Fatmin [94 (77–100) % V̇O2max] were observed in the majority of participants in response to the incremental exercise test to volitional exhaustion. Whole-body total fat oxidation rate was 0.8 ± 0.3 g/min at the end of steady-state exercise, with 43% of participants presenting rates of ≥1.0 g/min, despite the state of hyperglycemia above resting homeostatic range [mean (95%CI): 6.9 (6.7–7.2) mmol/L]. In response to the carbohydrate feeding interventions of 90 g/h 2:1 glucose–fructose formulation, 38% of participants showed breath H2 responses indicative of carbohydrate malabsorption. Greater gastrointestinal symptom severity and feeding intolerance was observed with higher carbohydrate intakes (90 vs. 76 g/h) during steady-state exercise and was greatest when high exercise intensity was performed (i.e., performance test). Endurance and ultra-endurance runners can attain relatively high rates of whole-body fat oxidation during exercise in a post-prandial state and with carbohydrate provisions during exercise, despite consuming a mixed macronutrient diet. Higher carbohydrate intake during exercise may lead to greater gastrointestinal symptom severity and feeding intolerance.

Ziel dieser Studie war, standardisiert erhobene Milchleistungs-, Stoffwechsel und Parameter zum Fortpflanzungsgeschehen in der ökologischen Milchviehhaltung auf mögliche Zusammenhänge zu verschiedenen Haltungssystemen zu prüfen. Hierfür standen Daten der elfmal jährlich stattfinden Milchleistungsprüfung (MLP) des Landeskuratoriums der Erzeugerringe für tierische Veredelung in Bayern e.V. (LKV) für den Zeitraum 2015–2017 zur Verfügung. Untersucht wurden 56 ökologische Milchviehbetriebe des Verbandes Naturland im bayerischen Alpenvorraum [31Anbindehaltungsbetriebe mit Weide (AH+W), 18Laufstallbetriebe mit Weide (LS+W), 7Laufstallbetriebe mit Auslauf (LS+A)]. Verglichen wurden Herdengröße, Milchleistung und Fett-Eiweiß-Quotient, Non-Return-Rate90, Rastzeit und Zwischenkalbezeit sowie der Anteil der Kühe mit Ketoserisiko. Für das Jahr 2017 lagen Informationen bezüglich der Zusammensetzung des Grundfutters vor, weshalb der Fokus auf diesem Jahr lag. Im Sommer war die errechnete Energiedichte des Grundfutters zwischen den Haltungssystemen annähernd gleich, im Winter dagegen lag die errechnete Energiedichte des Grundfutters in AH+W signifikant unter jener in LS+W und LS+A. Die LS+A-Betriebe konnten eine signifikant höhere Milchleistung (p

We model network formation in a firm. Agents learn about the quality of their working relationships with each other. Their good relationships become their networks. Accumulating relationships becomes increasingly costly, however. Over time agents become less open to forming relationships with others unknown to them, leading their networks to be front-loaded with agents they met near the beginning of their careers. The interaction of this dynamic with turnover yields predictions about the time pattern of history dependence in an agent’s network as a function of his tenure. Mutual openness of newly arrived agents in a firm also leads to the cross-section prediction of “cohort attachment,” a tendency for members of an agent’s hiring cohort to be disproportionately represented in his network. When members of a network formed within a firm are subsequently split across many firms, the desire to renew their successful working relationships can lead to job referrals. Former co-workers who provide referrals will be drawn disproportionately from the referred workers’ hiring cohorts at their previous employers.

A competitive 300-mm silicon photonics foundry technology has been developed by GLOBALFOUNDRIES for general availability, which takes advantage of advanced CMOS process technology and provides a manufacturing scale. A state-of-the-art process design kit offers a codesign environment with access to a comprehensive photonics device library along with a monolithically integrated SOI CMOS device library. Advances in automated wafer-level optical test enable statistical photonic device characterization for development, photonic modeling, and manufacturing controls. The key challenges and solutions in developing a manufacturable photonic technology with state-of-the-art performance are described, as well as a roadmap for next generation high-performance monolithic silicon photonics are outlined.

The objective of this study was to evaluate 2 different treatment procedures at the first milking after calving to increase colostrum quantity and to improve colostrum quality in dairy cows. We hypothesized that either exogenous treatment with oxytocin or the presence of the calf at first milking would lead to higher colostrum quantity and higher IgG concentration. The study was conducted from October to December 2017 on a commercial dairy farm in Germany. A total of 567 cows at the time of calving were enrolled, but for the final analyses only 521 animals were considered. The cows were randomly assigned on a daily basis into 1 of 3 groups: (1) control group (n = 177), (2) application of 20 IU of oxytocin i.m. (OXY; n = 163), and (3) presence of the calf (CA; n = 181) before and during milking. Cows in the control and oxytocin group had no contact with their calves after calving and were milked in a separate milking parlor. Cows in the oxytocin group were injected with 20 IU of oxytocin i.m. 3 min before manual stimulation. For cows in the third group, the calf was placed into a calf cart and located in front of the cow 3 min before manipulation of the cow. Colostrum quantity was determined by a digital hanging scale. The colostrum quality was assessed with digital Brix refractometry and ELISA. To evaluate the effect of 2 different treatment procedures, a generalized linear mixed model was constructed using SPSS (SPSS Inc., IBM, Ehningen, Germany). The mean (±SE) colostrum quantity was 4.17 ± 0.30 kg. The treatment procedures and the harvesting time after calving had no effect on colostrum quantity. Parity, calf birth weight, and calving time affected colostrum quantity. Cows in second parity had the lowest quantity of colostrum (3.74 ± 0.37 kg) compared with cows in parity 1 (4.75 ± 0.34 kg) and cows in parity 3 or greater (4.75 ± 0.38 kg). Cows calving during the night (2200 until 0600 h; 4.93 ± 0.37 kg) had the highest quantity of colostrum compared with cows calving in the morning (0600 until 1400 h; 4.17 ± 0.38 kg) or afternoon (1400 until 2200 h; 4.14 ± 0.34 kg). Regarding colostrum quality, 48% of the colostrum samples contained ≥50 mg of IgG/mL. The mean IgG concentration was 54.6 ± 2.80 mg of IgG/mL. Colostrum quality was affected by the treatment procedures, colostrum quantity, parity, calving time, harvesting time after calving, and the calving day during the week. Both treatment procedures (i.e., OXY with mean IgG concentration results of 57.0 mg of IgG/mL and CA with 56.0 mg of IgG/mL) resulted in higher IgG concentrations in colostrum compared with the control group (50.7 mg of IgG/mL). With increasing colostrum quantity, the colostrum quality decreased in primiparous and multiparous cows. A longer time lag between calving and milking negatively affected the colostrum quality. Concentration of IgG was higher for cows in parity 3 or greater (64.6 ± 2.59 mg of IgG/mL) compared with cows in parity 1 (48.5 ± 2.86 mg of IgG/mL) and cows in parity 2 (50.7 ± 2.89 mg of IgG/mL). Cows calving during the night had greater IgG concentrations (60.4 ± 2.92 mg of IgG/mL) compared with cows calving in the morning (51.9 ± 2.98 mg of IgG/mL) or afternoon (51.3 ± 2.71 mg of IgG/mL). Harvesting colostrum on quieter days, such as Sundays, resulted in higher IgG concentrations (61.4 ± 3.70 mg of IgG/mL). The assessment by Brix refractometry resulted in a mean result of 26.0 ± 0.20% Brix. Treatment procedures and the harvesting time after calving had no effect on colostrum quality. A negative association was observed between colostrum quantity and quality in primiparous and multiparous cows determined by Brix refractometry. Brix readings were greater for cows in parity 3 or higher (27.7 ± 0.26% Brix) compared with cows in parity 1 (25.3 ± 0.30% Brix) and cows in parity 2 (25.0 ± 0.32% Brix). In conclusion, the treatment procedure for the first milking is irrelevant to improve the quantity of colostrum. Both treatment procedures, however, increased IgG concentrations as determined by ELISA.

This translational research case series describes the implementation of a gastrointestinal assessment protocol during exercise (GastroAxEx) to inform individualised therapeutic intervention of endurance athletes affected by exercise-induced gastrointestinal syndrome (EIGS) and associated gastrointestinal symptoms (GIS). A four-phase approach was applied. Phase 1: Clinical assessment and exploring background history of exercise-associated gastrointestinal symptoms. Phase 2: Individual tailored GastroAxEx laboratory simulation designed to mirror exercise stress, highlighted in phase 1, that promotes EIGS and GIS during exercise. Phase 3: Individually programmed therapeutic intervention, based on the outcomes of Phase 2. Phase 4: Monitoring and readjustment of intervention based on outcomes from field testing under training and race conditions. Nine endurance athletes presenting with EIGS, and two control athletes not presenting with EIGS, completed Phase 2. Two athletes experienced significant thermoregulatory strain (peak core temperature attained > 40°C) during the GastroAxEx. Plasma cortisol increased substantially pre- to post-exercise inn= 6/7 (Δ > 500 nmol/L). Plasma I-FABP concentration increased substantially pre- to post-exercise inn= 2/8 (Δ > 1,000 pg/ml). No substantial change was observed in pre- to post-exercise for systemic endotoxin and inflammatory profiles in all athletes. Breath H2responses showed that orocecal transit time (OCTT) was delayed inn= 5/9 (90–150 min post-exercise) athletes, with the remaining athletes (n= 4/9) showing no H2turning point by 180 min post-exercise. Severe GIS during exercise was experienced inn= 5/9 athletes, of whichn= 2/9 had to dramatically reduce work output or cease exercise. Based on each athlete’s identified proposed causal factors of EIGS and GIS during exercise (i.e.,n= 9/9 neuroendocrine-gastrointestinal pathway of EIGS), an individualised gastrointestinal therapeutic intervention was programmed and advised, adjusted from a standard EIGS prevention and management template that included established strategies with evidence of attenuating EIGS primary causal pathways, exacerbation factors, and GIS during exercise. All participants reported qualitative data on their progress, which included their previously presenting GIS during exercise, such as nausea and vomiting, either being eliminated or diminished resulting in work output improving (i.e., completing competition and/or not slowing down during training or competition as a result of GIS during exercise). These outcomes suggest GIS during exercise in endurance athletes are predominantly related to gastrointestinal functional and feeding tolerance issues, and not necessarily gastrointestinal integrity and/or systemic issues. GastroAxEx allows for informed identification of potential causal pathway(s) and exacerbation factor(s) of EIGS and GIS during exercise at an individual level, providing a valuable informed individualised therapeutic intervention approach.

Customized Speech — speech targeted or tailored based on knowledge of one’s audience — is pervasive. It permeates our relationships, our culture, and, especially, our politics. Until recently, customization drew relatively little attention. Cambridge Analytica changed that. Since 2016, a consensus has decried Speech Customization as causing political manipulation, disunity, and destabilization. On this account, machine learning, social networks and Big Data make political Customized Speech a threat we constitutionally can, and normatively should, curtail. That view is mistaken. In this Article, I offer the first systematic analysis of Customized Speech and the First Amendment. I reach two provocative results: Doctrinally, the First Amendment robustly protects Speech Customization. And normatively, even amidst Big Data, this protection can help society and democracy. Doctrinally, the use of audience information to customize speech is, itself, core protected speech. Further, audience-information collection, while less protected, may still only be regulated by carefully drawn, content-neutral, generally applicable laws. And unless and until the state affirmatively enacts such laws (as, overwhelmingly, it has not), it may not curtail speakers’ otherwise-lawful use of such information in political Speech Customization. What does this mean for democratic government? Today, Customized Speech raises fears about democratic discourse, hyper-partisan factions, and citizen autonomy. But these are less daunting than the consensus suggests, and are offset by key benefits: modern Customized Speech activates the apathetic, empowers the marginalized, and checks government overreach. Accordingly, many current proposals to restrict such Customized Speech — from disclosure requirements to outright bans — are neither constitutionally viable nor normatively required.

The study aimed to determine the effect of diurnal versus nocturnal exercise on gastrointestinal integrity and functional responses, plasma lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) concentrations (as indirect indicators of endotoxin responses), systemic inflammatory cytokine profile, gastrointestinal symptoms, and feeding tolerance.Endurance runners (n = 16) completed 3 h of 60% V˙O2max (22.7°C, 45% relative humidity) running, on one occasion performed at 0900 h (400 lx; DAY) and on another occasion at 2100 h (2 lx; NIGHT). Blood samples were collected pre- and postexercise and during recovery to determine plasma concentrations of cortisol, catecholamines, claudin-3, I-FABP, LBP, and sCD14 and inflammatory cytokine profiles by ELISA. Orocecal transit time (OCTT) was determined by lactulose challenge test given at 150 min, with concomitant breath hydrogen (H2) and gastrointestinal symptom determination.Cortisol increased substantially pre- to postexercise on NIGHT (+182%) versus DAY (+4%) (trial-time, P = 0.046), with no epinephrine (+41%) and norepinephrine (+102%) trial differences. I-FABP, but not claudin-3, increased pre- to postexercise on both trials (mean = 2269 pg·mL-1, 95% confidence interval = 1351-3187, +143%) (main effect of time [MEOT], P0.001). sCD14 increased pre- to postexercise (trial-time, P = 0.045, +5.6%) and was greater on DAY, but LBP decreased (MEOT, P = 0.019, -11.2%) on both trials. No trial difference was observed for systemic cytokine profile (MEOT, P = 0.004). Breath H2 responses (P = 0.019) showed that OCTT was significantly delayed on NIGHT (84 min, with n = 3 showing no breath H2 turning point by 180 min postexercise) compared with DAY (mean = 54 min, 95% confidence interval = 29-79). NIGHT resulted in greater total gastrointestinal symptoms (P = 0.009) compared with DAY. No difference in feeding tolerance markers was observed between trials.Nocturnal exercise instigates greater gastrointestinal functional perturbations and symptoms compared with diurnal exercise. However, there are no circadian differences to gastrointestinal integrity and systemic perturbations in response to the same exertional stress and controlled procedures.

Studien belegen, dass finanzielle Aspekte eine bedeutende Rolle für tierschutzrelevante Themen spielen. Ziel der vorliegenden Studien war es, den aktuellen Stand von Tierkranken- und Tieroperationsversicherungen bei Hunden und Katzen aus Sicht von Tierärztinnen/Tierärzten und Tierhalterinnen/Tierhaltern zu untersuchen. In Studie1 wurden Tierärztinnen/Tierärzte (N=360) zu Tierversicherungen und tierschutzrelevanten Faktoren (wie etwa regelmäßige Behandlungen) befragt. Die Ergebnisse zeigten, dass sich die meisten Tierärztinnen/Tierärzte eindeutig für den Abschluss von Tierversicherungen aussprachen. Als Gründe wurden überwiegend tierschutzrelevante Aspekte genannt wie etwa weniger Behandlungseinschränkungen und Euthanasie aufgrund finanzieller Einschränkungen der Halterinnen/Halter. Schätzungen der Tierärztinnen/Tierärzte hinsichtlich der aktuellen Tierkranken- wie auch Tieroperationsversichertenquote lagen bei etwa 5% für Hunde und 2% für Katzen. Die Ergebnisse zeigten ferner, dass Tierärztinnen/Tierärzte den Tierschutz bei versicherten Tieren mehr gewährleistet sahen, da versicherte Tiere ihrer Einschätzung nach eine bessere medizinische Versorgung erhielten und regelmäßiger vorgestellt wurden (z.B. für Check-ups). Bei Studie2 wurden Tierhalterinnen/Tierhalter (N=1.340) zu Tierkranken- und Tieroperationsversicherungen sowie zur Häufigkeit von Krankheiten und Tierarztbesuchen befragt. Hier konnten die Teilnehmerinnen/Teilnehmer entscheiden, ob sie für ein aktuell lebendes Tier den Fragebogen beantworten wollten und/oder für einen Hund oder eine Katze, der/die innerhalb der letzten zehn Jahre verstorben ist. Die Ergebnisse der beiden Gruppen der Tierhalterinnen/Tierhalter zeigten, dass die Anzahl aktuell versicherter Tiere (verglichen mit in den letzten zehn Jahren bereits verstorbenen Tieren) höher war und zugleich die Zahlungsbereitschaft für Tierversicherungen niedriger war. Ferner zeigten auch diese Ergebnisse, dass versicherte Tiere eine bessere medizinische Versorgung erhielten und in der Tendenz eher eines natürlichen Todes starben als nicht-versicherte. Die Ergebnisse beider Studien fügen sich in den aktuellen Forschungsstand. Seit einigen Jahren zeichnet sich ein Trend zu mehr Tierversicherungen ab und tierschutzrelevante Aspekte rücken zunehmend in den Vordergrund. Eine Erklärung hierfür findet sich im Wandel der Tier-Mensch-Beziehung, wonach Haustiere zunehmend als Familienmitglieder erachtet werden. Allerdings bleibt festzuhalten, dass es hinsichtlich tierschutzrelevanter Aspekte einer differenzierten Betrachtung bedarf. So sind beispielsweise Behandlungen, auch wenn sie von einer Tierversicherung getragen werden würden, nicht automatisch im Sinne des Tierschutzes.

This work presents various device self-heating temperature sensing techniques and discusses their application in device reliability projection. Details of sensor design, technology choice, layout and ambient temperature impact on measurement results are discussed. The sensors produce excellent results which were confirmed through TCAD thermal simulation. Self-heating was studied by varying the number of fins per active region and proximity of sensor to heater was investigated. While most data presented here is on FinFET technology the learning and measurement techniques are applicable to planar technologies. Front-end-of-line (FEOL) reliability mechanism, hot carrier injection (HCI) was studied to show that self-heating effects can impact measurement results and recommendations are given on how to mitigate them. Self-heating is also studied for logic circuits by utilizing ring oscillators with several densities and stage counts to show that self-heating is considerably lower compared to constant voltage stress conditions conducted on discrete structures.

The objective of this study was to evaluate a filter system to harvest plasma to assess failure of passive transfer (FPT) in newborn calves. Blood samples (n = 227) for serum and plasma harvesting were collected via jugular vein puncture from Holstein calves aged 1 to 7 d from 4 commercial dairy herds in Northeast Germany. Serum IgG concentrations were determined using a sandwich ELISA. Failure of passive transfer was defined as IgG concentrations10 mg/mL and used as a gold standard. One handheld optical refractometer (Euromex Holland, Arnhem, the Netherlands) and 2 digital Brix refractometers (device 1: HI 96801 digital refractometer, Hanna Instruments, Woonsocket, RI; device 2: Misco PA201, Misco, Solon, OH) were used to analyze total proteins in serum or plasma. The colostrum uptake of the calf can thus be monitored and calves with FPT can be identified. Serum was obtained through centrifugation. Plasma was obtained through either a filter system or centrifugation. For plasma filtration, approximately 2 mL of lithium heparin blood was injected into the inlet reservoir of a plasma filter (2-Drop-Filter, Pharmadoc, Lübeck, Germany) using a disposable syringe. Receiver operating characteristic curve analyses were used to determine optimum thresholds for each of the 3 devices using different media. Sixty-seven (30%) calves had FPT. For the handheld optical refractometer, the optimum threshold was 5.6 g/dL [sensitivity 70.1%; specificity 80.0%; positive predictive value (PPV) 60.1%; negative predictive value (NPV) 86.2%; area under the curve (AUC) 0.85] using serum. For centrifuged plasma, the optimum threshold was 6.3 g/dL (sensitivity 82.1%; specificity 68.1%; PPV 52.5%; NPV 89.9%; AUC 0.84), and for filtered plasma, the threshold was 6.0 g/dL (sensitivity 56.7%; specificity 90.0%; PPV 70.9%; NPV 82.9%; AUC 0.80). For device 1, the optimum threshold was 8.9% Brix (sensitivity 82.1%; specificity 63.8%; PPV 48.7%; NPV 89.5%; AUC 0.81), 9.4% Brix (sensitivity 76.1%; specificity 73.7%; PPV 55.4%; NPV 87.8%; AUC 0.80), using serum and centrifuged plasma, respectively. For device 2, the optimum threshold was 8.7% Brix (sensitivity 74.6%; specificity 76.2%; PPV 57.4%; NPV 87.5%; AUC 0.83), 9.5% Brix (sensitivity 80.6%; specificity 70.6%; PPV 54.0%; NPV 89.5%; AUC 0.83), and 9.2% Brix (sensitivity 58.2%; specificity 87.5%; PPV 66.6%; NPV 83.0%; AUC 0.80) using serum, centrifuged plasma, and filtered plasma, respectively. Based on the AUC, the 3 devices yielded comparable test characteristics to identify calves with FPT. In conclusion, a filter system can be used to facilitate the evaluation of FPT as a point of care technique in calves without the need for serum centrifugation.

In this work, the RF reliability models that are developed using the Energy Driven Hot Carrier model are implemented using Cadence RelExpert and validated at both device level and circuit level. Accurate RF circuit level small signal degradation prediction is showcased for the first time using a cascode based LNA. This can help the designers to estimate the life time of the designs and improve designs up front to meet the design standards through simple simulation.

Debilitating gastrointestinal symptoms are a common feature of endurance running, and may be exacerbated by and (or) limit the ability to tolerate carbohydrate intake during exercise. The study aimed to determine whether two weeks of repetitive gut-challenge during running can reduce exercise associated gastrointestinal symptoms and carbohydrate malabsorption. Endurance runners (n= 18) performed an initial gut-challenge trial (GC1) comprising 2 h running exercise at 60% VO2max (steady state) whilst consuming a formulated gel-disc containing 30 g carbohydrates (2:1 glucose-fructose, 10% w/v) every 20 min, followed by a 1 h running effort bout. Gastrointestinal symptoms, feeding tolerance, and breath hydrogen (H2) were determined along the gut-challenge trial. After GC1, participants were randomly assigned to a blinded carbohydrate (CHO, 90 gCHO·h−1) or placebo (PLA, 0 gCHO·h−1) gut-training group. This comprised of consuming the group specific feeding intervention during 1 h running exercise at 60% VO2max equivalent, daily over a period of two weeks. Participants then repeated the gut-challenge trial (GC2). In GC2, a reduced gut discomfort (P= 0.012), total (P= 0.009), upper- (P= 0.015) and lower-gastrointestinal (P= 0.008) symptoms, and nausea (P= 0.05) were observed on CHO, but not PLA. Feeding tolerance did not differ between GC1 and GC2 on CHO and PLA. H2 peak was attenuated in GC2 (6 ± 3 ppm) compared to GC1 (13 ± 6 ppm) on CHO (P= 0.004), but not on PLA (GC1 11 ± 7 ppm, and GC2 10 ± 10 ppm). The effort bout distance was greater in GC2 (12.3 ± 1.3 km) compared with GC1 (11.7 ± 1.5 km) on CHO (P= 0.035) only. Two weeks of repetitive gut-challenge improves gastrointestinal symptoms and reduces carbohydrate malabsorption during endurance running, which may have performance implications. This article is protected by copyright. All rights reserved.

Due to gastrointestinal tract adaptability, the study aimed to determine the impact of gut-training protocol over 2 weeks on gastrointestinal status, blood glucose availability, fuel kinetics, and running performance. Endurance runners (n = 25) performed a gut-challenge trial (GC1), consisting of 2 h running exercise at 60% V̇O2maxwhilst consuming gel-discs containing 30 g carbohydrates (2:1 glucose/fructose, 10% w/v) every 20 min and a 1 h distance test. Participants were then randomly assigned to a carbohydrate gel-disc (CHO-S), carbohydrate food (CHO-F), or placebo (PLA) gut-training group for 2 weeks of repetitive gut-challenge intervention. Participants then repeated a second gut-challenge trial (GC2). Gastrointestinal symptoms reduced in GC2 on CHO-S (60%; p = 0.008) and CHO-F (63%; p = 0.046); reductions were greater than PLA (p < 0.05). H2peak was lower in GC2 on CHO-S (mean (CI): 6 (4–8) ppm) compared with CHO-F (9 (6–12) ppm) and PLA (12 (2–21) ppm) (trial × time: p < 0.001). Blood glucose concentration was higher in GC2 on CHO-S (7.2 (6.3–8.1) mmol·L−1) compared with CHO-F (6.1 (5.7–6.5) mmol·L−1) and PLA (6.2 (4.9–7.5) mmol·L−1) (trial × time: p = 0.015). No difference in oxidation rates, plasma I-FABP, and cortisol concentrations were observed between groups and trials. Distance test improved on CHO-S (5.2%) and CHO-F (4.3%) in GC2, but not on PLA (–2.1%) (trial × time: p = 0.009). Two weeks of gut-training with CHO-S and CHO-F improved gastrointestinal symptoms and running performance compared with PLA. CHO-S also reduced malabsorption and increased blood glucose availability during endurance running compared with PLA.

We report here the closed genomes of Salmonella enterica strains from the 2017–2018 multistrain, multistate kratom outbreak using single-molecule real-time DNA sequencing. Four of the genomes consist of one circular chromosome, and the fifth has a circular chromosome and a single plasmid.

Based on two linear deterministic demand models, the sales revenue function of a multivariate quadratic form is formulated in this paper to determine the optimal offline and online selling prices for a retailer in a monopolistic environment. The impacts of the uniform delivery lead time on the retailer’s optimal pricing scheme and profitability are analytically examined. A numerical study is conducted to demonstrate these impacts.

This contribution focuses on the technical design of autonomous outdoor transport systems operating on factory premises. Outdoor applications present a high degree of complexity, which is reflected in the technical design of these vehicles. The requirements they must fulfill are higher than for indoor applications. Hence, the results of the technical design are crucial to enable the correct use of such systems. Axiomatic Design hereby offers a methodological basis for the systematic derivation of solution parameters for the technical design of autonomous outdoor transport systems. Functional metrics are introduced in addition to the conventional Axiomatic Design method to support the formulation of functional requirements and to reduce the subjectivity in the design process. The technical design approach that was developed is applied in the form of a framework.

We extend our previously suggested drift-diffusion (DD)-based hot-carrier degradation model to the case of decananometer transistors. Special attention is paid to the effect of electron-electron scattering, which populates the high energy tail of the carrier distribution function, by using a rate balance equation. We compare the results of the DD-based model with the results obtained from a spherical harmonics expansion of the Boltzmann transport equation as well as experimental data. We also study the accuracy and limits of the applicability of the DD-based model and conclude that this model is able to capture hot-carrier degradation in nMOSFETs over a range of gate lengths from 65 to 300 nm with excellent accuracy.

Scholars investigating incumbent inertia have recently begun to examine the role that external constituents play in incumbents’ adoption of discontinuous technologies. However, this research stream...

This paper draws on household survey data from countries of all income levels to measure how average unemployment rates vary with income per capita. We document that unemployment is increasing with GDP per capita. Furthermore, we show that this fact is accounted for almost entirely by low-educated workers, whose unemployment rates are strongly increasing in GDP per capita, rather than by high-educated workers, whose unemployment rates are not correlated with income. To interpret these facts, we build a model with workers of heterogeneous ability and two sectors: a traditional sector, in which self-employed workers produce output without reward for ability; and a modern sector, in which firms hire in frictional labor markets, and output increases with ability. Countries differ exogenously in the productivity level of the modern sector. The model predicts that as productivity rises, the traditional sector shrinks, as progressively less-able workers enter the modern sector, leading to a rise in overall unemployment and in the ratio of low-educated to high-educated unemployment rates. Quantitatively, the model accounts for around one third of the cross-country patterns we document.

It is well established that employee spinoffs learn their parents’ technologies, but little is known about their demand-side learning. We exploit the identification in international trade data of parent markets (countries) to investigate whether exporting employee spinoffs of exporting parents have an advantage in accessing their parents’ markets over exporting comparison firms well positioned to learn those markets at arm’s length. We find that, controlling for the greater overlap of spinoffs with their parents’ export products, at entry spinoffs access 51 percent more parent markets than exporting firms in the same 4-digit industries and municipalities as the parents. This advantage shrinks monotonically with time, becoming statistically insignificant four years after entry, indicating that intrafirm learning provides spinoffs with a four-year head start over learning at arm’s length. Spinoffs do not overlap more than comparison firms with parent markets that the parents did not serve at spinoff entry, providing evidence against the alternative hypothesis that product overlap inadequately controls for greater technological similarity of spinoffs to parents. Firm entry into parent markets predicted by spinoff status does not lead to entry into “adjacent” markets the following year.

Although infrequently associated with illness in humans, Salmonella enterica, subsp. enterica serovar Kentucky is the most common non-clinical, non-human serovar reported in the United States, being largely found in poultry and poultry products, as well as being associated with cattle. This serovar is polyphyletic and can be separated into two groups, Group I and II, based on CRISPR-typing analysis. In Salmonella Kentucky isolates from human clinical samples in Pennsylvania, both lineages are equally represented. The goal of this study was to determine whether both groups were also represented in domestic food animals in Pennsylvania. We analysed the CRISPR arrays from 67 Salmonella Kentucky isolates used PCR and sequencing of CRISPR arrays or analysis of whole genome sequences to analyse the CRISPR arrays and Across a collection of 67 Salmonella Kentucky isolates that includes those collected from farms, veterinary clinical samples as well as isolates from retail meats, we show that Group I Salmonella Kentucky are the exclusive lineage present. We reveal that the specific subtype of over a quarter of these animal isolates are also found to be responsible for causing human salmonellosis in the same region over the same time period.