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Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.
Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria.
When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure.
The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.
Seasonal influenza virus epidemics have a major impact on healthcare systems. Data on population susceptibility to emerging influenza virus strains during the interepidemic period can guide planning for resource allocation of an upcoming influenza season. This study sought to assess the population susceptibility to representative emerging influenza virus strains collected during the interepidemic period. The microneutralisation antibody titers (MN titers) of a human serum panel against representative emerging influenza strains collected during the interepidemic period before the 2018/2019 winter influenza season (H1N1-inter and H3N2-inter) were compared with those against influenza strains representative of previous epidemics (H1N1-pre and H3N2-pre). A multifaceted approach, incorporating both genetic and antigenic data, was used in selecting these representative influenza virus strains for the MN assay. A significantly higher proportion of individuals had a ⩾four-fold reduction in MN titers between H1N1-inter and H1N1-pre than that between H3N2-inter and H3N2-pre (28.5% (127/445) vs. 4.9% (22/445), P < 0.001). The geometric mean titer (GMT) of H1N1-inter was significantly lower than that of H1N1-pre (381 (95% CI 339–428) vs. 713 (95% CI 641–792), P < 0.001), while there was no significant difference in the GMT between H3N2-inter and H3N2-pre. Since A(H1N1) predominated the 2018–2019 winter influenza epidemic, our results corroborated the epidemic subtype.
In this paper, we develop the isogeometric analysis of the dual boundary element method (IGA-DBEM) to solve the potential problem with a degenerate boundary. The non-uniform rational B-Spline (NURBS) based functions are employed to interpolate the geometry and physical function. To deal with the rank-deficiency problem due to the degenerate boundary, the hypersingular integral equation is introduced to promote the full rank for the influence matrix in the dual BEM. Finally, three numerical examples are given to verify the accuracy of our proposed method. Both circular and square domains subjected to the Dirichlet boundary condition are considered. The engineering problem containing a degenerate boundary is considered, e.g., a seepage flow problem with a sheet pile. Numerical results of the IGA-DBEM agree well with these of the exact solution and the original dual boundary element method.
Non-tuberculous mycobacterium encephalitis is rare. Since 2013, a global outbreak of Mycobacterium chimaera infection has been attributed to point-source contamination of heater cooler units used in cardiac surgery. Disseminated M. chimaera infection has presented many unique challenges, including non-specific clinical presentations with delays in diagnosis, and a high mortality rate among predominantly immunocompetent adults. Here, we describe three patients with fatal disseminated Mycobacterium chimaera infection showing initially non-specific, progressively worsening neurocognitive decline, including confusion, delirium, depression and apathy. Autopsy revealed widespread granulomatous encephalitis of the cerebrum, brain stem and spinal cord, along with granulomatous chorioretinitis. Cerebral involvement and differentiation between mycobacterial granulomas and microangiopathic changes can be assessed best on MRI with contrast enhancement. The prognosis of M. chimaera encephalitis appears to be very poor, but might be improved by increased awareness of this new syndrome and timely antimicrobial treatment.
This presentation will enable the learner to:
1.Describe the clinical, radiological and neuropathological findings of Mycobacterium chimaera encephalitis
2.Be aware of this rare form of encephalitis, and explain its diagnosis, prognosis and management
Global inequity in access to and availability of essential mental health services is well recognized. The mental health treatment gap is approximately 50% in all countries, with up to 90% of people in the lowest-income countries lacking access to required mental health services. Increased investment in global mental health (GMH) has increased innovation in mental health service delivery in LMICs. Situational analyses in areas where mental health services and systems are poorly developed and resourced are essential when planning for research and implementation, however, little guidance is available to inform methodological approaches to conducting these types of studies. This scoping review provides an analysis of methodological approaches to situational analysis in GMH, including an assessment of the extent to which situational analyses include equity in study designs. It is intended as a resource that identifies current gaps and areas for future development in GMH. Formative research, including situational analysis, is an essential first step in conducting robust implementation research, an essential area of study in GMH that will help to promote improved availability of, access to and reach of mental health services for people living with mental illness in low- and middle-income countries (LMICs). While strong leadership in this field exists, there remain significant opportunities for enhanced research representing different LMICs and regions.
Copy number variations (CNVs), as an important source of genetic variation, can affect a wide range of phenotypes by diverse mechanisms. The somatostatin receptor 2 (SSTR2) gene plays important roles in cell proliferation and apoptosis. Recently, this gene was mapped to a CNV region, which encompasses quantitative trait loci of cattle economic traits including body weight, marbling score, etc. Therefore, SSTR2 CNV may exhibit phenotypic effects on cattle growth traits. In the current study, distribution of SSTR2 gene CNVs was investigated in six Chinese cattle breeds (XN, QC, NY, JA, LX and PN), and the results showed higher CNV polymorphisms in XN, QC and NY cattle. Next, association analysis between growth traits and SSTR2 CNV was performed for XN, QC and NY cattle. In NY, individuals with fewer copies showed better performance than those with more copies. Further, the effects of SSTR2 CNV on the SSTR2 mRNA level were also investigated, but revealed no significant correlation in either muscle or adipose tissue of adult NY cattle. The results suggested the potential for use of SSTR2 CNV as a marker for the molecular breeding of NY cattle.
Imprinted genes uniquely drive and support fetoplacental growth by controlling the allocation of maternal resources to the fetus and affecting the newborn’s growth. We previously showed that alterations of the placental imprinted gene expression are associated with suboptimal perinatal growth and respond to environmental stimuli including socio-economic determinants. At the same time, maternal psychosocial stress during pregnancy (MPSP) has been shown to affect fetal growth. Here, we set out to test the hypothesis that placental imprinted gene expression mediates the effects of MPSP on fetal growth in a well-characterized birth cohort, the Stress in Pregnancy (SIP) Study. We observed that mothers experiencing high MPSP deliver infants with lower birthweight (P=0.047). Among the 109 imprinted genes tested, we detected panels of placental imprinted gene expression of 23 imprinted genes associated with MPSP and 26 with birthweight. Among these genes, five imprinted genes (CPXM2, glucosidase alpha acid (GAA), GPR1, SH3 and multiple ankyrin repeat domains 2 (SHANK2) and THSD7A) were common to the two panels. In multivariate analyses, controlling for maternal age and education and gestational age at birth and infant gender, two genes, GAA and SHANK2, each showed a 22% mediation of MPSP on fetal growth. These data provide new insights into the role that imprinted genes play in translating the maternal stress message into a fetoplacental growth pattern.
An experiment was conducted to determine the effects of supplementing different amounts of daidzein in a diet on the growth performance, blood biochemical parameters and meat quality of finishing beef cattle. Thirty finishing Xianan steers were distributed in three groups equilibrated by weight and fed three different dietary treatments (concentrate ratio = 80%): (1) control; (2) 500 mg/kg daidzein and (3) 1000 mg/kg daidzein, respectively. Steers were slaughtered after an 80-day feeding trial. Results showed that daidzein supplementation had no effect on the final body weight, average daily gain and feed conversion rate of steers. Steers fed with 1000 mg/kg daidzein had greater dry matter intake than those fed with control diets. Compared with the control group, the 1000 mg/kg daidzein group had a higher fat thickness, lower shear force and lightness. The pH, drip loss, cooking loss, redness (a*), yellowness (b*), moisture, ash, crude protein and intramuscular fat of the Longissimus dorsi muscle were unaffected by daidzein supplementation. Compared with the control group, the 1000 mg/kg daidzein group significantly increased the serum concentrations of insulin, free fatty acid and Glutamic-pyruvic transaminase. The 500 mg/kg daidzein group significantly increased the serum concentration of tetraiodothyronine compared with the control group. Supplemental daidzein did not affect the blood antioxidant ability and blood immune parameters in serum. In conclusion, daidzein supplementation above 500 mg/day modifies feed intake and metabolic and hormonal profile, with positive and negative effects on meat quality.
To determine the burden of skin and soft tissue infections (SSTI), the nature of antimicrobial prescribing and factors contributing to inappropriate prescribing for SSTIs in Australian aged care facilities, SSTI and antimicrobial prescribing data were collected via a standardised national survey. The proportion of residents prescribed ⩾1 antimicrobial for presumed SSTI and the proportion whose infections met McGeer et al. surveillance definitions were determined. Antimicrobial choice was compared to national prescribing guidelines and prescription duration analysed using a negative binomial mixed-effects regression model. Of 12 319 surveyed residents, 452 (3.7%) were prescribed an antimicrobial for a SSTI and 29% of these residents had confirmed infection. Topical clotrimazole was most frequently prescribed, often for unspecified indications. Where an indication was documented, antimicrobial choice was generally aligned with recommendations. Duration of prescribing (in days) was associated with use of an agent for prophylaxis (rate ratio (RR) 1.63, 95% confidence interval (CI) 1.08–2.52), PRN orders (RR 2.10, 95% CI 1.42–3.11) and prescription of a topical agent (RR 1.47, 95% CI 1.08–2.02), while documentation of a review or stop date was associated with reduced duration of prescribing (RR 0.33, 95% CI 0.25–0.43). Antimicrobial prescribing for SSTI is frequent in aged care facilities in Australia. Methods to enhance appropriate prescribing, including clinician documentation, are required.
Identifying routes of transmission among hospitalized patients during a healthcare-associated outbreak can be tedious, particularly among patients with complex hospital stays and multiple exposures. Data mining of the electronic health record (EHR) has the potential to rapidly identify common exposures among patients suspected of being part of an outbreak.
We retrospectively analyzed 9 hospital outbreaks that occurred during 2011–2016 and that had previously been characterized both according to transmission route and by molecular characterization of the bacterial isolates. We determined (1) the ability of data mining of the EHR to identify the correct route of transmission, (2) how early the correct route was identified during the timeline of the outbreak, and (3) how many cases in the outbreaks could have been prevented had the system been running in real time.
Correct routes were identified for all outbreaks at the second patient, except for one outbreak involving >1 transmission route that was detected at the eighth patient. Up to 40 or 34 infections (78% or 66% of possible preventable infections, respectively) could have been prevented if data mining had been implemented in real time, assuming the initiation of an effective intervention within 7 or 14 days of identification of the transmission route, respectively.
Data mining of the EHR was accurate for identifying routes of transmission among patients who were part of the outbreak. Prospective validation of this approach using routine whole-genome sequencing and data mining of the EHR for both outbreak detection and route attribution is ongoing.
In several lately published studies, the association between single-nucleotide polymorphism (SNP, rs12252) of IFITM3 and the risk of influenza is inconsistent. To further understand the association between the SNP of IFITM3 and the risk of influenza, we searched related studies in five databases including PubMed published earlier than 9 November 2017. Ten sets of data from nine studies were included and data were analysed by Revman 5.0 and Stata 12.0 in our updated meta-analysis, which represented 1365 patients and 5425 no-influenza controls from four different ethnicities. Here strong association between rs12252 and influenza was found in all four genetic models. The significant differences in the allelic model (C vs. T: odds ratio (OR) = 1.35, 95% confidence interval (CI) (1.03–1.79), P = 0.03) and homozygote model (CC vs. TT: OR = 10.63, 95% CI (3.39–33.33), P < 0.00001) in the Caucasian subgroup were discovered, which is very novel and striking. Also novel discoveries were found in the allelic model (C vs. T: OR = 1.37, 95% CI (1.08–1.73), P = 0.009), dominant model (CC + CT vs. TT: OR = 1.48, 95% CI (1.08–2.02), P = 0.01) and homozygote model (CC vs. TT: OR = 2.84, 95% CI (1.36–5.92), P = 0.005) when we compared patients with mild influenza with healthy individuals. Our meta-analysis suggests that single-nucleotide T to C polymorphism of IFITM3 associated with increasingly risk of severe and mild influenza in both Asian and Caucasian populations.
This study investigated Echinococcus genotypes in patients with hydatidosis that reside in Inner Mongolia, Tibet or Qinghai Province by partially sequencing the cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase 1 (nad1) genes. Cyst fluids were collected from 23 patients with hydatidosis and DNA was extracted. Portions of the cox1 and nad1 genes were amplified and subsequently sequenced. Sequencing analysis determined that one of the isolates contained Echinococcus multilocularis, and the other 22 isolates contained E. granulosus sensu lato. The isolates were then further classified based on genotype, and E. granulosus sensu stricto (s.s.) G1 (n = 20), E. granulosus s.s. G3 (n = 1) and E. canadensis G6/7 (n = 1) were identified. Additionally, the sequences were concatenated (pcox1 + pnad1) and 11 haplotypes were identified among the E. granulosus s.s. isolates (G1 and G3), with a shared common haplotype (H1) identified. Overall, these findings provide further understanding of the genetic patterns of Echinococcus in western and northern China.
The increasing tropospheric ozone concentration [O3] strongly affects plant growth. However, the response of belowground processes in rice (Oryza sativa L.) systems to higher O3 is not well understood. The grain production, belowground biomass partitioning, root morphology and activity of rice (cv. Shanyou 63) were investigated in a free-air O3 enrichment platform at four key growth stages. Elevated O3 (EO3, 50% above the ambient O3) significantly decreased the grain yield and total biomass at the grain milky mature stage, root biomass at the tillering stage and root to shoot ratios (RRS) at the flowering and grain filling stages. The effects of EO3 on root morphology and activity varied among rice growth stage. EO3 significantly decreased root length, density, area, diameter and volume at the flowering stage, but EO3 significantly decreased various root morphological indices at the tillering, grain filling and milky mature stages. EO3 significantly increased the specific root respiration rate (root activity) and root respiration rate (autotrophic respiration) at grain filling and milky mature stages. Higher root autotrophic respiration and lower RRS in response to EO3 would reduce allocation of assimilated carbon to root growth, adversely affecting rice productivity. Our findings are critical for understanding the O3-induced impairment of belowground processes and carbon cycling in rice cropping systems and breeding of O3-tolerant cultivars under higher [O3] scenarios.
Introduction: The ECG diagnosis of acute coronary occlusion (ACO) in the setting of ventricular paced rhythm (VPR) is purported to be impossible. However, VPR has a similar ECG morphology to LBBB. The validated Smith-modified Sgarbossa criteria (MSC) have high sensitivity (Sens) and specificity (Spec) for ACO in LBBB. MSC consist of 1 of the following in 1 lead: concordant ST Elevation (STE) 1 mm, concordant ST depression 1 mm in V1-V3, or ST/S ratio <−0.25 (in leads with 1 mm STE). We hypothesized that the MSC will have higher Sens for diagnosis of ACO in VPR when compared to the original Sgarbossa criteria. We report preliminary findings of the Paced Electrocardiogram Requiring Fast Emergency Coronary Therapy (PERFECT) study Methods: The PERFECT study is a retrospective, multicenter, international investigation of ED patients from 1/2008 - 12/2016 with VPR on the ECG and symptoms suggestive of acute coronary syndrome (e.g. chest pain or shortness of breath). Data from four sites are presented. Acute myocardial infarction (AMI) was defined by the Third Universal Definition of AMI. A blinded cardiologist adjudicated ACO, defined as thrombolysis in myocardial infarction score 0 or 1 on coronary angiography; a pre-defined subgroup of ACO patients with peak cardiac troponin (cTn) >100 times the 99% upper reference limit (URL) of the cTn assay was also analyzed. Another blinded physician measured all ECGs. Statistics were by Mann Whitney U, Chi-square, and McNemars test. Results: The ACO and No-AMI groups consisted of 15 and 79 encounters, respectively. For the ACO and No-AMI groups, median age was 78 [IQR 72-82] vs. 70 [61-75] and 13 (86%) vs. 48 (61%) patients were male. The median peak cTn ratio (cTn/URL) was 260 [33-663] and 0.5 [0-1.3] for ACO vs. no-AMI. The Sens and Spec for the MSC and the original Sgarbossa criteria were 67% (95%CI 39-87) vs. 46% (22-72; p=0.25) and 99% (92-100) vs. 99% (92-100; p=0.5). In pre-defined subgroup analysis of ACO patients with peak cTn >100 times the URL (n=10), the Sens was 90% (54-100) for the MSC vs. 60% (27- 86) for original Sgarbossa criteria (p=0.25). Conclusion: ACO in VPR is an uncommon condition. The MSC showed good Sens for diagnosis of ACO in the presence of VPR, especially among patients with high peak cTn, and Spec was excellent. These methods and results are consistent with studies that have used the MSC to diagnose ACO in LBBB.
In this essay, we discuss the under-representation of women in leadership positions in global health (GH) and the importance of mentorship to advance women's standing in the field. We then describe the mentorship model of GROW, Global Research for Women. We describe the theoretical origins of the model and an adapted theory of change explaining how the GROW model for mentorship advances women's careers in GH. We present testimonials from a range of mentees who participated in a pilot of the GROW model since 2015. These mentees describe the capability-enhancing benefits of their mentorship experience with GROW. Thus, preliminary findings suggest that the GROW mentorship model is a promising strategy to build women's leadership in GH. We discuss supplemental strategies under consideration and next steps to assess the impact of GROW, providing the evidence to inform best practices for curricula elsewhere to build women's leadership in GH.
Multiple human immunodeficiency virus (HIV)-1 genotypes in China were first discovered in Yunnan Province before disseminating throughout the country. As the HIV-1 epidemic continues to expand in Yunnan, genetic characteristics and transmitted drug resistance (TDR) should be further investigated among the recently infected population. Among 2828 HIV-positive samples newly reported in the first quarter of 2014, 347 were identified as recent infections with BED-captured enzyme immunoassay (CEIA). Of them, 291 were successfully genotyped and identified as circulating recombinant form (CRF)08_BC (47.4%), unique recombinant forms (URFs) (18.2%), CRF01_AE (15.8%), CRF07_BC (14.4%), subtype C (2.7%), CRF55_01B (0.7%), subtype B (0.3%) and CRF64_BC (0.3%). CRF08_BC and CRF01_AE were the predominant genotypes among heterosexual and homosexual infections, respectively. CRF08_BC, URFs, CRF01_AE and CRF07_BC expanded with higher prevalence in central and eastern Yunnan. The recent common ancestor of CRF01_AE, CRF07_BC and CRF08_BC dated back to 1983.1, 1992.1 and 1989.5, respectively. The effective population sizes (EPS) for CRF01_AE and CRF07_BC increased exponentially during 1991–1999 and 1994–1999, respectively. The EPS for CRF08_BC underwent two exponential growth phases in 1994–1998 and 2001–2002. Lastly, TDR-associated mutations were identified in 1.8% of individuals. These findings not only enhance our understanding of HIV-1 evolution in Yunnan but also have implications for vaccine design and patient management strategies.
With the rapid development of telescopes, both temporal cadence and the spatial resolution of observations are increasing. This in turn generates vast amount of data, which can be efficiently searched only with automated detections in order to derive the features of interest in the observations. A number of automated detection methods and algorithms have been developed for solar activities, based on the image processing and machine learning techniques. In this paper, after briefly reviewing some automated detection methods, we describe our efficient and versatile automated detection method for solar filaments. It is able not only to recognize filaments, determine the features such as the position, area, spine, and other relevant parameters, but also to trace the daily evolution of the filaments. It is applied to process the full disk Hα data observed in nearly three solar cycles, and some statistic results are presented.
We present a variational optimization method that can identify the most efficient kinematic dynamo in a sphere, where efficiency is based on the value of a magnetic Reynolds number that uses enstrophy to characterize the inductive effects of the fluid flow. In this large-scale optimization, we restrict the flow to be steady and incompressible, and the boundary of the sphere to be no-slip and electrically insulating. We impose these boundary conditions using a Galerkin method in terms of specifically designed vector field bases. We solve iteratively for the flow field and the accompanying magnetic eigenfunction in order to find the minimal critical magnetic Reynolds number
for the onset of a dynamo. Although nonlinear, this iteration procedure converges to a single solution and there is no evidence that this is not a global optimum. We find that
is at least three times lower than that of any published example of a spherical kinematic dynamo generated by steady flows, and our optimal dynamo clearly operates above the theoretical lower bounds for dynamo action. The corresponding optimal flow has a spatially localized helical structure in the centre of the sphere, and the dominant components are invariant under rotation by