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Given the challenges in accurately identifying unexposed controls in case–control studies of diarrhoea, we examined diarrhoea incidence, subclinical enteric infections and growth stunting within a reference population in the Global Enteric Multicenter Study, Kenya site. Within ‘control’ children (0–59 months old without diarrhoea in the 7 days before enrolment, n = 2384), we examined surveys at enrolment and 60-day follow-up, stool at enrolment and a 14-day post-enrolment memory aid for diarrhoea incidence. At enrolment, 19% of controls had ⩾1 enteric pathogen associated with moderate-to-severe diarrhoea (‘MSD pathogens’) in stool; following enrolment, many reported diarrhoea (27% in 7 days, 39% in 14 days). Controls with and without reported diarrhoea had similar carriage of MSD pathogens at enrolment; however, controls reporting diarrhoea were more likely to report visiting a health facility for diarrhoea (27% vs. 7%) or fever (23% vs. 16%) at follow-up than controls without diarrhoea. Odds of stunting differed by both MSD and ‘any’ (including non-MSD pathogens) enteric pathogen carriage, but not diarrhoea, suggesting control classification may warrant modification when assessing long-term outcomes. High diarrhoea incidence following enrolment and prevalent carriage of enteric pathogens have implications for sequelae associated with subclinical enteric infections and for design and interpretation of case–control studies examining diarrhoea.
The present study aimed to identify the factors that affect immediate (within 24 h after farrowing onset) postnatal piglet mortality in litters with hyperprolific sows, and investigate their associations with behaviour of postpartum sows in two different farrowing housing systems. A total of 30 sows were housed in: (1) CRATE (n=15): the farrowing crate closed (0.80×2.20 m) within a pen (2.50×1.70 m), and (2) OPEN (n=15): the farrowing crate open (0.80×2.20×1.80 m) within a pen (2.50×2.40 m) with a provision of 20 ls of hay in a rack. A total of 518 live born piglets, produced from the 30 sows, were used for data analyses during the first 24 h after the onset of parturition (T24). Behavioural observations of the sows were assessed via video analyses during T24. Total and crushed piglet mortality rates were higher in OPEN compared with CRATE (P<0.01, for both). During T24, the OPEN sows tended to show higher frequency of postural changes (P=0.07) and duration of standing (P=0.10), and showed higher frequencies of bar-biting (P<0.05) and piglet trapping (P<0.01), when compared with the CRATE sows. During T24, the mortality rates caused by crushing were correlated with the piglet trapping event (r=0.93, P<0.0001), postural changes (r=0.37, P<0.01), duration of standing (r=0.32, P<0.01) and frequency of bar-biting behaviour (r=0.51, P<0.01) of the sows (n=30). In conclusion, immediate postnatal piglet mortality, mainly due to crushing, may be associated with potential increases in frequency of postural changes, duration of standing and incidence of piglet trapping in postpartum sows in the open crate system with large litters.
The dynamics of two rectangular, flexible plates of low aspect ratio
(height/width = 4) was experimentally investigated in tandem arrangements under uniform flows at various Cauchy numbers
is the fluid density,
is the incoming flow velocity,
is the Young’s modulus and
is the second moment of the area) and spacings
, 1 and 2. Planar particle image velocimetry (PIV) and particle tracking velocimetry (PTV) were used to characterize the surrounding flow field and oscillations of the wall-mounted structures. Results show that the oscillations of the upstream plate were dominated by its natural frequency. However, the motions of the downstream plate were significantly modulated by the induced flow and coherent motions shed from the upstream structure. Such modulation led to highly correlated motions between the plates with similar amplitude in the case
, to comparatively larger oscillation amplitude of the downstream plate in the intermediate separation
, and roughly decoupled interaction for
. Despite that the intensity of the oscillations of the upstream plate increased monotonically with
, this was not the case for the downstream plate at
and 2 due to flow fluctuations, vortex shedding and large structure deformation; as a result, it exhibited a local minimum. Supported with measurements, a mathematical model was derived to quantitatively explain this behaviour.
Background: In RRMS patients with inadequate response to prior therapy, 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved outcomes versus SC IFNB-1a over 2 years (CARE-MS II [NCT00548405]). Efficacy remained durable in a 4-year extension (NCT00930553); patients could receive as-needed alemtuzumab retreatment (≥12 months apart) for disease activity, or another disease-modifying therapy (DMT). Through Year 6, 88% remained on study; 50% received neither alemtuzumab retreatment nor another DMT; 16% received ≥4 courses; 3% received ≥5 courses. We evaluated Course 4 (C4) efficacy in patients receiving ≥4 courses. Methods: Annualized relapse rate (ARR); improved/stable Expanded Disability Status Scale (EDSS) score (versus baseline); 6-month confirmed disability improvement (CDI). 11% of patients met inclusion criteria: ≥4 courses within 60 months of baseline; no DMT. Those receiving C5 were censored at that time. Results: ARR decreased after C4 (12 months pre-C4 [-12M]: 0.75; 12 months post-C4 [+12M]: 0.19; P<0.0001), remaining low (0.23) at Year 3 post-C4. More patients had stable/improved EDSS scores +12M (67.5%) versus at C4 administration (53.5%). Percentage with CDI increased post-C4 (-12M: 10.0%; +12M: 26.7%). Conclusions: C4 reduced relapses and stabilized/improved disability in patients with disease activity after initial treatment (C1, C2) plus one additional course (C3).
Background: To determine whether exosomal microRNAs (miRNAs) in CSF of patients with FTD can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic FTD Initiative (GENFI) cohort and in sporadic FTD. Methods: GENFI participants were either carriers of a pathogenic mutation or at risk of carrying a mutation because a first-degree relative was a symptomatic mutation carrier. Exosomes were isolated from CSF of 23 -pre-symptomatic and 15 symptomatic mutation carriers, and 11 healthy non-mutation carriers. Expression of miRNAs was measured using qPCR arrays. MiRNAs differentially expressed in symptomatic compared to pre-symptomatic mutation carriers were evaluated in 17 patients with sporadic FTD, 13 patients with sporadic Alzheimer’s disease (AD), and 10 healthy controls (HCs). Results: In the GENFI cohort, miR-204-5p and miR-632 were significantly decreased in symptomatic compared to pre-symptomatic mutation carriers. Decrease of miR-204-5p and miR-632 revealed receiver operator characteristics with an area of 0.89 [90% CI: 0.79-0.98] and 0.81 [90% CI: 0.68-0.93], and when combined an area of 0.93 [90% CI: 0.87-0.99]. In sporadic FTD, only miR-632 was significantly decreased compared to sporadic AD and HCs. Decrease of miR-632 revealed an area of 0.89 [90% CI: 0.80-0.98]. Conclusions: Exosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD.
Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector (RRV). RRVs selectively infect cancer cells due to innate and adaptive immune response defects in cancers that allow virus replication, and the requirement for cell division for virus integration into the genome. Toca 511 spreads through tumors, stably delivering an optimized yeast cytosine deaminase gene that converts the prodrug Toca FC (investigational, extended-release 5-FC) into 5-FU within the tumor microenvironment. 5-FU kills infected dividing cancer cells and surrounding tumor, myeloid derived suppressor cells, and tumor associated macrophages, resulting in long-term tumor immunity in preclinical models. Data from a Phase 1 resection trial showed six durable CRs and extended mOS compared to historical controls. The FDA granted Breakthrough Therapy Designation for Toca 511 & Toca FC in the treatment of patients with rHGG. Toca 5 is an international, randomized, open-label Phase 3 trial (NCT02414165) of Toca 511 & Toca FC versus SOC in patients undergoing resection for first or second recurrence of rHGG. Patients will be stratified by IDH1 status, KPS, and geographic region. Primary endpoint is OS, and secondary endpoints are durable response rate, durable clinical benefit rate, duration of durable response, and 12-month survival rate. Key inclusion criteria are histologically proven GBM or AA, tumor size ≥1cm and ≤5cm, and KPS ≥70. Immune monitoring and molecular profiling will be performed. Approximately 380 patients will be randomized. An IDMC is commissioned to review the safety and efficacy data which includes 2 interim analyses. Enrollment is ongoing.
Introduction: Patients with Heart failure (HF) experience frequent decompensation necessitating multiple emergency department (ED) visits and hospitalizations. If patients are able to receive timely interventions and optimize self-management, recurrent ED visits may be reduced. In this feasibility study, we piloted the application of home telemonitoring to support the discharge of HF patients from hospital to home. We hypothesized that TEC4Home would decrease ED revisits and hospital admissions and improve patient health outcomes. Methods: Upon discharge from the ED or hospital, patients with HF received a blood pressure cuff, weight scale, pulse oximeter, and a touchscreen tablet. Participants submitted measurements and answered questions on the tablet about their HF symptoms daily for 60 days. Data were reviewed by a monitoring nurse. From November 2016 to July 2017, 69 participants were recruited from Vancouver General Hospital (VGH), St. Pauls Hospital (SPH) and Kelowna General Hospital (KGH). Participants completed pre-surveys at enrollement and post-surveys 30 days after monitoring finished. Administrative data related to ED visits and hospital admissions were reviewed. Interviews were conducted with the monitoring nurses to assess the impact of monitoring on patient health outcomes. Results: A preliminary analysis was conducted on a subsample of participants (n=22) enrolled across all 3 sites by March 31, 2017. At VGH and SPH (n=14), 25% fewer patients required an ED visit in the post-survey reporting compared to pre-survey. During the monitoring period, the monitoring nurse observed seven likely avoided ED admissions due to early intervention. In total, admissions were reduced by 20% and total hospital length of stay reduced by 69%. At KGH (n=8), 43% fewer patients required an ED visit in the post-survey reporting compared to the pre-survey. Hospital admissions were reduced by 20% and total hospital length of stay reduced by 50%. Overall, TEC4Home participants from all sites showed a significant improvement in health-related quality of life and in self-care behaviour pre- to 90 days post-monitoring. A full analysis of the 69 patients will be complete in February 2018. Conclusion: Preliminary findings indicate that home telemonitoring for HF patients can decrease ED revisits and improve patient experience. The length of stay data may also suggest the potential for early discharge of ED patients with home telemonitoring to avoid or reduce hospitalization. A stepped-wedge randomized controlled trial of TEC4Home in 22 BC communities will be conducted in 2018 to generate evidence and scale up the service in urban, regional and rural communities. This work is submitted on behalf of the TEC4Home Healthcare Innovation Community.
Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.
This study evaluated the annual prevalence of anogenital warts (AGW) caused by human papillomavirus (HPV) and analysed the trend in annual per cent changes (APC) by using national claims data from the Health Insurance Review and Assessment of Korea, 2007–2015. We also estimated the socio-economic burden and co-morbidities of AGW. All analyses were performed based on data for primary A63.0, the specific diagnosis code for AGW. The socio-economic cost of AGW was calculated based on the direct medical cost, direct non-medical cost and indirect cost. The overall AGW prevalence and socio-economic burden has increased during the last 9 years. However, the prevalence of AGW differed significantly by sex. The female prevalence increased until 2012, and decreased thereafter (APC + 3·6%). It would fall after the introduction of routine HPV vaccination, principally for females, in Korea. The male prevalence increased continuously over time (APC + 11·6%), especially in those aged 20–49 years. Referring to the increasing AGW prevalence and its disease burden, active HPV infection control surveillance and prevention in males are worth consideration.
The overall objective of our work is to assess the relative contributions of plant enzymes and rumen microbes to rumen degradation of freshly-ingested herbage. In situ techniques have been used extensively to compare rumen degradation characteristics of feeds, though there remain technical problems associated with microbial contamination of residues after incubation. We hypothesised that techniques to study microbial contamination might also provide insights into microbial colonisation. Our earlier studies (Lee et al., 1999) identified distinctive odd-chain fatty acids that could be used as microbial markers. A dacron bag study was conducted to examine the influence of dacron bag rinsing techniques on DM disappearance and microbial contamination in residues from fresh grass, assessed using odd-chain fatty acids as markers.
We describe the design and performance of the Engineering Development Array, which is a low-frequency radio telescope comprising 256 dual-polarisation dipole antennas working as a phased array. The Engineering Development Array was conceived of, developed, and deployed in just 18 months via re-use of Square Kilometre Array precursor technology and expertise, specifically from the Murchison Widefield Array radio telescope. Using drift scans and a model for the sky brightness temperature at low frequencies, we have derived the Engineering Development Array’s receiver temperature as a function of frequency. The Engineering Development Array is shown to be sky-noise limited over most of the frequency range measured between 60 and 240 MHz. By using the Engineering Development Array in interferometric mode with the Murchison Widefield Array, we used calibrated visibilities to measure the absolute sensitivity of the array. The measured array sensitivity matches very well with a model based on the array layout and measured receiver temperature. The results demonstrate the practicality and feasibility of using Murchison Widefield Array-style precursor technology for Square Kilometre Array-scale stations. The modular architecture of the Engineering Development Array allows upgrades to the array to be rolled out in a staged approach. Future improvements to the Engineering Development Array include replacing the second stage beamformer with a fully digital system, and to transition to using RF-over-fibre for the signal output from first stage beamformers.
We sought to comprehensively assess the prevalence and outcomes of complications associated with Staphylococcus aureus bacteremia (SAB) in children. Secondarily, prevalence of methicillin resistance and outcomes of complications from methicillin-resistant S. aureus (MRSA) vs. methicillin-susceptible S. aureus SAB were assessed. This is a single-center cross-sectional study of 376 patients ⩽18 years old with SAB in 1990–2014. Overall, 197 (52%) patients experienced complications, the most common being osteomyelitis (33%), skin and soft tissue infection (31%), and pneumonia (25%). Patients with complications were older (median 3 vs. 0·7 years, P = 0·05) and more had community-associated SAB (66% vs. 34%, P = 0·001). Fewer patients with complications had a SAB-related emergency department or hospital readmission (10% vs. 19%, P = 0·014). Prevalence of methicillin resistance increased from 1990–1999 to 2000–2009, but decreased in 2010–2014. Complicated MRSA bacteremia resulted in more intensive care unit admissions (66% vs. 47%, P = 0·03) and led to increased likelihood of having ⩾2 foci (58% vs. 26%, P < 0·001). From multivariate analysis, community-associated SAB increased risk and concurrent infections decreased risk of complications (odds ratio (OR) 1·82 (1·1–3·02), P = 0·021) and (OR 0·58 (0·34–0·97), P = 0·038), respectively. In conclusion, children with SAB should be carefully evaluated for complications. Methicillin resistance remains associated with poor outcomes but have decreased in overall prevalence.
The Yale–Potsdam Stellar Isochrones (YaPSI) cover the low and intermediate stellar mass regime (0.15 to 5.0 M⊙) for a wide range of solar-scaled chemical compositions (metallicity from −0.5 to +0.3; helium mass fraction from 0.25 to 0.37, assigned independently of each other). The tracks are finely spaced in mass, to allow for accurate interpolation. The models feature state-of-the-art input physics relevant to low-mass stars modeling (surface boundary conditions, equation of state), thus updating the faint end of the Yonsei-Yale (YY) isochrones. Utility codes, such as an isochrone interpolator in age, metallicity and helium content, are also provided. The YaPSI isochrones are in good agreement with the empirical mass–luminosity and mass–radius relations available to date, and provide satisfactory fitting of the color-magnitude diagrams of well-studied open clusters.
Introduction: ST-elevation myocardial infarction (STEMI) presenting to the ED is a significant health burden. The provision of IV morphine with doses titrated to provide comfort is recommended in the AHA STEMI Guidelines, yet there is limited evidence of safety in this setting. The primary objective of this study was to measure potential harm associated with the provision of IV morphine in STEMI patients presenting to the ED. Methods: This was a two centre retrospective chart review from an urban, inner city, academic ED with an annual census of 85,000 visits, and an affiliated community hospital with 35,000 annual visits. Consecutive patients from April 2009 to January 2015 presenting to the 2 EDs with a diagnosis of STEMI were identified in the ED database. Eight trained research assistants, blinded to the study hypothesis, used standardized data collection templates. The primary investigator double collected 20% of all data to ensure completeness and accuracy. Results: We included 311 patients with STEMI (124 received morphine [M]; 187 no morphine [nM]). The ages of the two groups were similar (mean 64 yrs [M] & 67 yrs [nM]; median 63 yrs [M] & 66 yrs [nM]; IQR 45-81 [M] and 45.5-86.5 [nM]); as were the proportion of female patients (21.0% [M] & 23.5% [nM]. The pre-STEMI Charlson comorbidity scores (mean 2.6), median time to first ECG (11 min [M] & 16 min [nM]), and mean time-to-needle for PCI (96.8 min [M] & 92.0 min [nM]) were similar between groups. The mean CCU length of stay (LOS) (9.3 days vs 6.3 days) and hospital LOS (7.4 days vs 4.6 days) were longer for patients receiving morphine than those not receiving morphine. Rates of congestive heart failure, acute kidney injury and cardiac arrest in hospital were unchanged between the groups. Unadjusted mortality was similar (10.5% [M] vs 13.3% [nM]) between groups. Binary logistic regression controlling for age, Charlson score, first and peak troponin values demonstrated an association between receiving morphine in the ED and an increased risk of death at 30 days (OR 8.1; 95% CI 7.1.-9.1). Conclusion: The provision of morphine to patients with STEMI in the ED may be associated with increased CCU and hospital LOS. When controlling for age, pre-STEMI Charlson score, first and peak troponin values, receiving morphine was associated with an increased risk of death at 30 days. Further research to elucidate this association is warranted.
Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset.
Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA.
Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) < 0.01]. The structure of EPDS responses significantly differed between Europe and the USA (∆*CFI > 0.01), but not between European countries (∆*CFI < 0.01).
Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.
The Antarctic Roadmap Challenges (ARC) project identified critical requirements to deliver high priority Antarctic research in the 21st century. The ARC project addressed the challenges of enabling technologies, facilitating access, providing logistics and infrastructure, and capitalizing on international co-operation. Technological requirements include: i) innovative automated in situ observing systems, sensors and interoperable platforms (including power demands), ii) realistic and holistic numerical models, iii) enhanced remote sensing and sensors, iv) expanded sample collection and retrieval technologies, and v) greater cyber-infrastructure to process ‘big data’ collection, transmission and analyses while promoting data accessibility. These technologies must be widely available, performance and reliability must be improved and technologies used elsewhere must be applied to the Antarctic. Considerable Antarctic research is field-based, making access to vital geographical targets essential. Future research will require continent- and ocean-wide environmentally responsible access to coastal and interior Antarctica and the Southern Ocean. Year-round access is indispensable. The cost of future Antarctic science is great but there are opportunities for all to participate commensurate with national resources, expertise and interests. The scope of future Antarctic research will necessitate enhanced and inventive interdisciplinary and international collaborations. The full promise of Antarctic science will only be realized if nations act together.