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To develop and validate the Discrepancy-based Evidence for Loss of Thinking Abilities (DELTA) score. The DELTA score characterizes the strength of evidence for cognitive decline on a continuous spectrum using well-established psychometric principles for improving detection of cognitive changes.
DELTA score development used neuropsychological test scores from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort (two tests each from Memory, Executive Function, and Language domains). We derived regression-based normative reference scores using age, gender, years of education, and word-reading ability from robust cognitively normal ADNI participants. Discrepancies between predicted and observed scores were used for calculating the DELTA score (range 0–15). We validated DELTA scores primarily against longitudinal Clinical Dementia Rating-Sum of Boxes (CDR-SOB) and Functional Activities Questionnaire (FAQ) scores (baseline assessment through Year 3) using linear mixed models and secondarily against cross-sectional Alzheimer’s biomarkers.
There were 1359 ADNI participants with calculable baseline DELTA scores (age 73.7 ± 7.1 years, 55.4% female, 100% white/Caucasian). Higher baseline DELTA scores (stronger evidence of cognitive decline) predicted higher baseline CDR-SOB (ΔR2 = .318) and faster rates of CDR-SOB increase over time (ΔR2 = .209). Longitudinal changes in DELTA scores tracked closely and in the same direction as CDR-SOB scores (fixed and random effects of mean + mean-centered DELTA, ΔR2 > .7). Results were similar for FAQ scores. High DELTA scores predicted higher PET-Aβ SUVr (ρ = 324), higher CSF-pTau/CSF-Aβ ratio (ρ = .460), and demonstrated PPV > .9 for positive Alzheimer’s disease biomarker classification.
Data support initial development and validation of the DELTA score through its associations with longitudinal functional changes and Alzheimer’s biomarkers. We provide several considerations for future research and include an automated scoring program for clinical use.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
To understand how exposure to victimization during adolescence and the presence of comorbid psychological conditions influence substance use treatment entry and substance use disorder diagnosis from 14 to 25 years old among serious juvenile offenders, this study included 1,354 serious juvenile offenders who were prospectively followed over 7 years. Growth mixture modeling was used to assess profiles of early victimization during adolescence (14–17 years). Discrete time survival mixture analysis was used to assess time to treatment entry and substance use disorder diagnosis. Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) were used as predictors of survival time. Mixture models revealed three profiles of victimization: sustained poly-victimization, moderate/decreasing victimization, and low victimization. Youth in the sustained poly-victimization class were more likely to enter treatment earlier and have a substance use diagnosis earlier than other classes. PTSD was a significant predictor of treatment entry for youth in the sustained poly-victimization class, and MDD was a significant predictor of substance use disorder diagnosis for youth in the moderate/decreasing victimization class. Therefore, substance use prevention programming targeted at youth experiencing poly-victimization in early adolescence—especially those who have PTSD or MDD—is needed.
The objective of this study was to investigate the impact of the most commonly cited factors that may have influenced infants’ gut microbiota profiles at one year of age: mode of delivery, breastfeeding duration and antibiotic exposure. Barcoded V3/V4 amplicons of bacterial 16S-rRNA gene were prepared from the stool samples of 52 healthy 1-year-old Australian children and sequenced using the Illumina MiSeq platform. Following the quality checks, the data were processed using the Quantitative Insights Into Microbial Ecology pipeline and analysed using the Calypso package for microbiome data analysis. The stool microbiota profiles of children still breastfed were significantly different from that of children weaned earlier (P<0.05), independent of the age of solid food introduction. Among children still breastfed, Veillonella spp. abundance was higher. Children no longer breastfed possessed a more ‘mature’ microbiota, with notable increases of Firmicutes. The microbiota profiles of the children could not be differentiated by delivery mode or antibiotic exposure. Further analysis based on children’s feeding patterns found children who were breastfed alongside solid food had significantly different microbiota profiles compared to that of children who were receiving both breastmilk and formula milk alongside solid food. This study provided evidence that breastfeeding continues to influence gut microbial community even at late infancy when these children are also consuming table foods. At this age, any impacts from mode of delivery or antibiotic exposure did not appear to be discernible imprints on the microbial community profiles of these healthy children.
The aim of this retrospective review was to assess the overall burden and trend in spinal tuberculosis (TB) at tertiary hospitals in the Western Cape Province of South Africa. All spinal TB cases seen at the province's three tertiary hospitals between 2012 and 2015 were identified and clinical records of each case assessed. Cases were subsequently classified as bacteriologically confirmed or clinically diagnosed and reported with accompanying clinical and demographic information. Odds ratios (OR) for severe spinal disease and corrective surgery in child vs. adult cases were calculated. A total of 393 cases were identified (319 adults, 74 children), of which 283 (72%) were bacteriologically confirmed. Adult cases decreased year-on-year (P = 0.04), however there was no clear trend in child cases. Kyphosis was present in 60/74 (81%) children and 243/315 (77%) adults with available imaging. Corrective spinal surgery was performed in 35/74 (47%) children and 80/319 (25%) adults (OR 2.7, 95% confidence interval 1.6–4.5, P = 0.0003). These findings suggest that Western Cape tertiary hospitals have experienced a substantial burden of spinal TB cases in recent years with a high proportion of severe presentation, particularly among children. Spinal TB remains a public health concern with increased vigilance required for earlier diagnosis, especially of child cases.
Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.
We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.
Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.
Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.
The development of laser wakefield accelerators (LWFA) over the past several years has led to an interest in very compact sources of X-ray radiation – such as “table-top” free electron lasers. However, the use of conventional undulators using permanent magnets also implies system sizes which are large. In this work, we assess the possibilities for the use of novel mini-undulators in conjunction with a LWFA so that the dimensions of the undulator become comparable with the acceleration distances for LWFA experiments (i.e., centimeters). The use of a prototype undulator using laser machining of permanent magnets for this application is described and the emission characteristics and limitations of such a system are determined. Preliminary electron propagation and X-ray emission measurements are taken with a LWFA electron beam at the University of Michigan.
Salmonella prevalence in UK pigs is amongst the highest in Europe, highlighting the need to investigate pig farms which have managed to maintain a low Salmonella seroprevalence. A total of 19 pig farms that had a consistently low (<10%) seroprevalence over 4 years (named Platinum farms) were compared against 38 randomly selected Control farms, chosen to match the same distribution of production types and geographical distribution of the Platinum farms. Each farm was visited and floor faeces and environmental samples were collected. It was shown that Control farms had a significantly higher median percentage of pooled faecal samples positive for Salmonella compared with the Platinum farms (12.1% and 0.4% for pooled faecal samples, respectively) and were more likely to have serovars of public health importance detected (S. Typhimurium/ monophasic variants or S. Enteritidis). Considering the comprehensive on-farm sampling, the identification of farms negative for Salmonella, along with the identification of those that had maintained low prevalence over a long period is important. The risk factor analyses identified pelleted feed, feed deliveries crossing farm perimeter and regular antibiotic use as associated with being a Control farm. Performance data indicated that Platinum farms were performing better for slaughter live weight than Controls. Limited assessments of available pig movement records suggested that the source of pigs was not key to Platinum status, but further study would be needed to confirm this finding. These results emphasise that maintaining very low prevalence on UK farms is achievable.
The Taipan galaxy survey (hereafter simply ‘Taipan’) is a multi-object spectroscopic survey starting in 2017 that will cover 2π steradians over the southern sky (δ ≲ 10°, |b| ≳ 10°), and obtain optical spectra for about two million galaxies out to z < 0.4. Taipan will use the newly refurbished 1.2-m UK Schmidt Telescope at Siding Spring Observatory with the new TAIPAN instrument, which includes an innovative ‘Starbugs’ positioning system capable of rapidly and simultaneously deploying up to 150 spectroscopic fibres (and up to 300 with a proposed upgrade) over the 6° diameter focal plane, and a purpose-built spectrograph operating in the range from 370 to 870 nm with resolving power R ≳ 2000. The main scientific goals of Taipan are (i) to measure the distance scale of the Universe (primarily governed by the local expansion rate, H0) to 1% precision, and the growth rate of structure to 5%; (ii) to make the most extensive map yet constructed of the total mass distribution and motions in the local Universe, using peculiar velocities based on improved Fundamental Plane distances, which will enable sensitive tests of gravitational physics; and (iii) to deliver a legacy sample of low-redshift galaxies as a unique laboratory for studying galaxy evolution as a function of dark matter halo and stellar mass and environment. The final survey, which will be completed within 5 yrs, will consist of a complete magnitude-limited sample (i ⩽ 17) of about 1.2 × 106 galaxies supplemented by an extension to higher redshifts and fainter magnitudes (i ⩽ 18.1) of a luminous red galaxy sample of about 0.8 × 106 galaxies. Observations and data processing will be carried out remotely and in a fully automated way, using a purpose-built automated ‘virtual observer’ software and an automated data reduction pipeline. The Taipan survey is deliberately designed to maximise its legacy value by complementing and enhancing current and planned surveys of the southern sky at wavelengths from the optical to the radio; it will become the primary redshift and optical spectroscopic reference catalogue for the local extragalactic Universe in the southern sky for the coming decade.
Anecdotal evidence has suggested that outdoor-kept pigs show an improvement to health and productivity after being moved to a new site. This study explores whether Salmonella occurrence reduced and was sustained after moving to a new site. Nine farms were followed for a year in which four sampling visits were completed. The highest detection of Salmonella was from pooled faecal dropping from pigs, run-off/ pooled water, rodents and wild birds. Descriptive summaries showed that the prevalence of both all Salmonella and serovars of public health importance were lower at all visits after the move. Some variability was shown in results from individual farms, but a year after the move, six farms still maintained a lower prevalence. A risk factor model showed that the prevalence at visits 2 and 3 after the move was significantly lower than baseline, after accounting for a number of significant factors that were included in the model. These were sample type and seasonality (included as a priori), presence of coughing in the sampled group and Glasser's disease on the farm, and the use of tent or kennel accommodation. This finding provides important evidence that more frequent site moves may help reduce Salmonella prevalence in outdoor herds.
Individuals with chronic respiratory conditions may be at increased risk for pertussis. We conducted a retrospective administrative claims analysis to examine the incidence and economic burden of diagnosed pertussis among adolescents and adults in the USA with chronic obstructive pulmonary disease (COPD) or asthma. Patients aged ⩾11 years with diagnosed pertussis and pre-existing COPD (n = 343) or asthma (n = 1041) were matched 1:1 to patients with diagnosed pertussis but without COPD or asthma. Differences in all-cause costs (‘excess’ costs) during the 45-day and 3-month and 6-month periods before and after the pertussis index date were calculated; adjusted excess costs were estimated via multivariate regressions. The incidence of diagnosed pertussis was higher among patients with COPD or asthma than among matched patients. Compared with matched patients, patients with pertussis and pre-existing COPD or asthma accrued greater all-cause adjusted costs across study periods ($3694 and $1193 more, respectively, in the 45-day period; $4173 and $1301 more in the 3-month period; and $6154 and $1639 more in the 6-month period; all P < 0·0001). Patients with pre-existing COPD or asthma experience an increased economic burden after diagnosed pertussis and may especially benefit from targeted tetanus, diphtheria, and acellular pertussis vaccination strategies.
We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38–17·40), prior MRSA infection (OR 3·59; 95% CI 1·05–12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7–159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08–0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.
The staffing of ambulances with different levels of Emergency Medical Service (EMS) providers is a difficult decision with evidence being mixed on the benefit of each model.
The objective of this study was to describe a pilot program evaluating alternative staffing on two ambulances utilizing the paramedic-basic (PB) model (staffed with one paramedic and one emergency medical technician[EMT]).
This was a retrospective study conducted from September 17, 2013 through December 31, 2013. The PB ambulances were compared to geographically matched ambulances staffed with paramedic-paramedic (PP ambulances). One PP and one PB ambulance were based at Station A; one PP and one PB ambulance were based at Station B. The primary outcome was total on-scene time. Secondary outcomes included time-to-electrocardiogram (EKG), time-to-intravenous (IV) line insertion, IV-line success rate, and percentage of protocol violations. Inclusion criteria were all patients requesting prehospital services that were attended to by these teams. Patients were excluded if they were not attended to by the study ambulance vehicles. Descriptive statistics were reported as medians and interquartile ranges (IQR). Proportions were reported with 95% confidence intervals (CI). The Mann-Whitley U test was used for significance testing (P<.05).
Median on-scene times at Station A for the PP ambulance were shorter than the PB ambulance team (PP: 10.1 minutes, IQR 6.0-15; PB: 13.0 minutes, IQR 8.1-18; P=.01). This finding also was noted at Station B (PP: 13.5 minutes, IQR 8.5-19; PB: 14.3 minutes, IQR 9.9-20; P=.01). There were no differences between PP and PB ambulance teams at Station A or Station B in time-to-EKG, time-to-IV insertion, IV success rate, and protocol violation rates.
In the setting of a well-developed EMS system utilizing an all-Advanced Life Support (ALS) response, this study suggests that PB ambulance teams may function well when compared to PP ambulances. Though longer scene times were observed, differences in time to ALS interventions and protocol violation rates were not different. Hybrid ambulance teams may be an effective staffing alternative, but decisions to use this model must address clinical and operational concerns.
CortezEJ, PanchalAR, DavisJE, KesegDP. The Effect of Ambulance Staffing Models in a Metropolitan, Fire-Based EMS System. Prehosp Disaster Med. 2017;32(2):175–179.
TiO2 nanotubular structures were formed on titanium foils through anodic oxidation using an electrolyte of Ethyleneglycol-H2O (97:3 Vol %)+0.25 M NH4F at a constant voltage of 60V. The anodized samples were analyzed in a FE-SEM obtaining the geometric parameters of the nanotubular arrays. The diameter and the length of the nanotubes were 112 nm and 65µm |respectively, whereas the wall thickness was 44 nm. Crystalline phase of TiO2 nanotubular films (TNTF) were determined by XRD after annealing at 500°C for 2 h, resulting high intensity peaks of anatase and low intensity peaks of rutile. Then, the crystallized samples were characterized from an optical, photoelectrochemical and photocatalytic point of view. The photoelectrochemical measurements were carried out in 0.5 M Na2SO4 solution using an 8 W UV lamp at a λ= 365 nm, which results were recorded at 0 bias during 10 min under darkness and illumination intervals of 1 min each. Photocatalytic performance of the TNTF was explored with a 10 mg/L methyl orange solution using an UV light at a wavelength of 365 nm. The changes in the concentration of the MO solution was determined from the calibration curve determined from the absorption spectra at different concentrations of MO (from 0.1 mg/L to 20 mg/L). It was observed an efficiency yield of 99.8% in the photocatalytic performance in presence of the TNTF.
Behavioral traits generally show moderate to strong genetic influence, with heritability estimates of around 50%. Some recent research has suggested that trust may be an exception because it is more strongly influenced by social interactions. In a sample of over 7,000 adolescent twins from the United Kingdom's Twins Early Development Study, we found broad sense heritability estimates of 57% for generalized trust and 51% for trust in friends. Genomic-relatedness-matrix restricted maximum likelihood (GREML) estimates in the same sample indicate that 21% of the narrow sense genetic variance can be explained by common single nucleotide polymorphisms for generalized trust and 43% for trust in friends. As expected, this implies a large amount of unexplained heritability, although power is low for estimating DNA-based heritability. The missing heritability may be accounted for by interactions between DNA and the social environment during development or via gene–environment correlations with rare variants. How these genes and environments correlate seem especially important for the development of trust.
Medulloblastoma (MB) is the most common malignant pediatric brain tumour, and is categorized into four molecular subgroups, with Group 3 MB having the worst prognosis due to the highest rate of metastatic dissemination and relapse. In this work, we describe the epigenetic regulator Bmi1 as a novel therapeutic target for treatment of recurrent Group 3 MB. Through comparative profiling of primary and recurrent MB, we show that Bmi1 defines a treatment-refractory cell population that is uniquely targetable by a novel class of small molecule inhibitors. We have optimized an in vivo mouse-adapted therapy model that has the advantage of generating recurrent, human, treatment-refractory MBs. Our preliminary studies showed that although chemoradiotherapy administered to mice engrafted with human MB showed reduction in tumour size, Bmi1 expression was enriched in the post-treatment residual tumour. Furthermore, we found that knockdown of Bmi1 in human recurrent MB cells decreases proliferation and self-renewing capacities of MB cells in vitro as well as both tumour size and extent of spinal leptomeningeal metastases in vivo. Oral administration of a potent Bmi1 inhibitor, PTC 028, resulted in a marked reduction in tumour burden and an increased survival in treatment cohort. Bmi1 inhibitors showed high specificity for MB cells and spared normal human neural stem cells, when treated with doses relevant for MB cells. As Group 3 medulloblastoma is often metastatic and uniformly fatal at recurrence, with no current or planned trials of targeted therapy, an efficacious agent such as Bmi1 inhibitor could be rapidly transitioned to clinical trials.
To determine the impact of total household decolonization with intranasal mupirocin and chlorhexidine gluconate body wash on recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection among subjects with MRSA skin and soft-tissue infection.
Three-arm nonmasked randomized controlled trial.
Five academic medical centers in Southeastern Pennsylvania.
Adults and children presenting to ambulatory care settings with community-onset MRSA skin and soft-tissue infection (ie, index cases) and their household members.
Enrolled households were randomized to 1 of 3 intervention groups: (1) education on routine hygiene measures, (2) education plus decolonization without reminders (intranasal mupirocin ointment twice daily for 7 days and chlorhexidine gluconate on the first and last day), or (3) education plus decolonization with reminders, where subjects received daily telephone call or text message reminders.
MAIN OUTCOME MEASURES
Owing to small numbers of recurrent infections, this analysis focused on time to clearance of colonization in the index case.
Of 223 households, 73 were randomized to education-only, 76 to decolonization without reminders, 74 to decolonization with reminders. There was no significant difference in time to clearance of colonization between the education-only and decolonization groups (log-rank P=.768). In secondary analyses, compliance with decolonization was associated with decreased time to clearance (P=.018).
Total household decolonization did not result in decreased time to clearance of MRSA colonization among adults and children with MRSA skin and soft-tissue infection. However, subjects who were compliant with the protocol had more rapid clearance