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Geophytes are hardy, resilient plants that are tolerant of cold temperatures and drought and are well documented as a reliable food source for hunter-gatherers worldwide. Human settlement patterns and foraging behaviors have long been associated with the use of nutrient-dense geophytes rich in carbohydrates, fiber, vitamins, and minerals. Indigenous communities in the northern Great Basin developed cultural practices centered around gathering, preparing, and consuming important geophytic plants. These practices became deeply embedded in their cultural identity, forming rituals, stories, and traditions that persist today. Although there is strong ethnographic precedent for the significance of geophytes, finding evidence of their use in the archaeological record remains a challenge. This study analyzed archaeological starch residue extracted from bedrock metates in the uplands of Warner Valley, Oregon. Systematic studies of starch granules collected from extant plant communities growing near archaeological sites were applied to the identification of archaeological granules. Starch granules from geophytes, specifically Lomatium spp. (biscuitroot), were identified on metate surfaces at all sites, thus providing direct evidence for the collection and processing of geophyte vegetables. Evidence of geophyte plant processing on bedrock metates contributes to archaeological theories about subsistence strategies, food-processing technologies, social organization, and cultural practices in past human societies.
Clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) for treatment of treatment-resistant depression (TRD) vary widely and there is no mood rating scale that is standard for assessing rTMS outcome. It remains unclear whether TMS is as efficacious in older adults with late-life depression (LLD) compared to younger adults with major depressive disorder (MDD). This study examined the effect of age on outcomes of rTMS treatment of adults with TRD. Self-report and observer mood ratings were measured weekly in 687 subjects ages 16–100 years undergoing rTMS treatment using the Inventory of Depressive Symptomatology 30-item Self-Report (IDS-SR), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item, and Hamilton Depression Rating Scale 17-item (HDRS). All rating scales detected significant improvement with treatment; response and remission rates varied by scale but not by age (response/remission ≥ 60: 38%–57%/25%–33%; <60: 32%–49%/18%–25%). Proportional hazards models showed early improvement predicted later improvement across ages, though early improvements in PHQ and HDRS were more predictive of remission in those < 60 years (relative to those ≥ 60) and greater baseline IDS burden was more predictive of non-remission in those ≥ 60 years (relative to those < 60). These results indicate there is no significant effect of age on treatment outcomes in rTMS for TRD, though rating instruments may differ in assessment of symptom burden between younger and older adults during treatment.
Maintaining attention underlies many aspects of cognition and becomes compromised early in neurodegenerative diseases like Alzheimer’s disease (AD). The consistency of maintaining attention can be measured with reaction time (RT) variability. Previous work has focused on measuring such fluctuations during in-clinic testing, but recent developments in remote, smartphone-based cognitive assessments can allow one to test if these fluctuations in attention are evident in naturalistic settings and if they are sensitive to traditional clinical and cognitive markers of AD.
Method:
Three hundred and seventy older adults (aged 75.8 +/− 5.8 years) completed a week of remote daily testing on the Ambulatory Research in Cognition (ARC) smartphone platform and also completed clinical, genetic, and conventional in-clinic cognitive assessments. RT variability was assessed in a brief (20-40 seconds) processing speed task using two different measures of variability, the Coefficient of Variation (CoV) and the Root Mean Squared Successive Difference (RMSSD) of RTs on correct trials.
Results:
Symptomatic participants showed greater variability compared to cognitively normal participants. When restricted to cognitively normal participants, APOE ε4 carriers exhibited greater variability than noncarriers. Both CoV and RMSSD showed significant, and similar, correlations with several in-clinic cognitive composites. Finally, both RT variability measures significantly mediated the relationship between APOE ε4 status and several in-clinic cognition composites.
Conclusions:
Attentional fluctuations over 20–40 seconds assessed in daily life, are sensitive to clinical status and genetic risk for AD. RT variability appears to be an important predictor of cognitive deficits during the preclinical disease stage.
Background: The late-onset cerebellar ataxias (LOCAs) have until recently resisted molecular diagnosis. Contributing to this diagnostic gap is that non-coding structural variations, such as repeat expansions, are not fully accessible to standard short-read sequencing analysis. Methods: We combined bioinformatics analysis of whole-genome sequencing and long-read sequencing to search for repeat expansions in patients with LOCA. We enrolled 66 French-Canadian, 228 German, 20 Australian and 31 Indian patients. Pathogenic mechanisms were studied in post-mortem cerebellum and induced pluripotent stem cell (iPSC)-derived motor neurons from 2 patients. Results: We identified 128 patients who carried an autosomal dominant GAA repeat expansion in the first intron of the FGF14 gene. The expansion was present in 61%, 18%, 15% and 10% of patients in the French-Canadian, German, Australian and Indian cohorts, respectively. The pathogenic threshold was determined to be (GAA)≥250, although incomplete penetrance was observed in the (GAA)250-300 range. Patients developed a slowly progressive cerebellar syndrome at an average age of 59 years. Patient-derived post-mortem cerebellum and induced motor neurons both showed reduction in FGF14 RNA and protein expression compared to controls. Conclusions: This intronic, dominantly inherited GAA repeat expansion in FGF14 represents one of the most common genetic causes of LOCA uncovered to date.
Smartphones have the potential for capturing subtle changes in cognition that characterize preclinical Alzheimer’s disease (AD) in older adults. The Ambulatory Research in Cognition (ARC) smartphone application is based on principles from ecological momentary assessment (EMA) and administers brief tests of associative memory, processing speed, and working memory up to 4 times per day over 7 consecutive days. ARC was designed to be administered unsupervised using participants’ personal devices in their everyday environments.
Methods:
We evaluated the reliability and validity of ARC in a sample of 268 cognitively normal older adults (ages 65–97 years) and 22 individuals with very mild dementia (ages 61–88 years). Participants completed at least one 7-day cycle of ARC testing and conventional cognitive assessments; most also completed cerebrospinal fluid, amyloid and tau positron emission tomography, and structural magnetic resonance imaging studies.
Results:
First, ARC tasks were reliable as between-person reliability across the 7-day cycle and test-retest reliabilities at 6-month and 1-year follow-ups all exceeded 0.85. Second, ARC demonstrated construct validity as evidenced by correlations with conventional cognitive measures (r = 0.53 between composite scores). Third, ARC measures correlated with AD biomarker burden at baseline to a similar degree as conventional cognitive measures. Finally, the intensive 7-day cycle indicated that ARC was feasible (86.50% approached chose to enroll), well tolerated (80.42% adherence, 4.83% dropout), and was rated favorably by older adult participants.
Conclusions:
Overall, the results suggest that ARC is reliable and valid and represents a feasible tool for assessing cognitive changes associated with the earliest stages of AD.
Wet winter conditions can create animal welfare issues in feedlots if the pen surface becomes a deep, wet, penetrable substrate. Feedlot pens with a clay and gravel base (N = 30) bedded with 150 mm (W15) and 300 mm (W30) depth of woodchips were compared to a control treatment with no bedding over a 109-day feeding period, while irrigated to supplement natural rainfall. The pad substrate was measured for variables which would affect cattle comfort and value of the substrate for composting. The penetrable depth of control pens was higher than both woodchip-bedded treatments from week 2, and increased until the end of the experiment. Meanwhile these scores were steady for W30 throughout the experiment, and increased for W15 only after week 10. Moisture content of the pad was higher throughout the experiment in the control pens than in the woodchip-bedded pens. In the control pens, the force required to pull a cattle leg analogue out of the pen substrate was three times that required in woodchip-bedded treatments. The W15 treatment increased C : N in the substrate to the upper limit of suitability for composting, and in W30, C : N was too high for composting after a 109-day feeding period. Overall, providing feedlot cattle with 150 or 300 mm of woodchip bedding during a 109-day feeding period improved the condition of the pad substrate for cattle comfort by reducing penetrable depth and moisture content of the substrate surface stratum, but composting value decreased in W30 over this feeding period duration.
Bloodstream infections (BSIs) are a frequent cause of morbidity in patients with acute myeloid leukemia (AML), due in part to the presence of central venous access devices (CVADs) required to deliver therapy.
Objective:
To determine the differential risk of bacterial BSI during neutropenia by CVAD type in pediatric patients with AML.
Methods:
We performed a secondary analysis in a cohort of 560 pediatric patients (1,828 chemotherapy courses) receiving frontline AML chemotherapy at 17 US centers. The exposure was CVAD type at course start: tunneled externalized catheter (TEC), peripherally inserted central catheter (PICC), or totally implanted catheter (TIC). The primary outcome was course-specific incident bacterial BSI; secondary outcomes included mucosal barrier injury (MBI)-BSI and non-MBI BSI. Poisson regression was used to compute adjusted rate ratios comparing BSI occurrence during neutropenia by line type, controlling for demographic, clinical, and hospital-level characteristics.
Results:
The rate of BSI did not differ by CVAD type: 11 BSIs per 1,000 neutropenic days for TECs, 13.7 for PICCs, and 10.7 for TICs. After adjustment, there was no statistically significant association between CVAD type and BSI: PICC incident rate ratio [IRR] = 1.00 (95% confidence interval [CI], 0.75–1.32) and TIC IRR = 0.83 (95% CI, 0.49–1.41) compared to TEC. When MBI and non-MBI were examined separately, results were similar.
Conclusions:
In this large, multicenter cohort of pediatric AML patients, we found no difference in the rate of BSI during neutropenia by CVAD type. This may be due to a risk-profile for BSI that is unique to AML patients.
Mitral valve perforation is an uncommon aetiology of mitral regurgitation in the paediatric population. We present a case where 3-dimensional echocardiography assisted in the diagnosis of the source of mitral regurgitation and the surgical correlation.
In order to inform core performance projections and divertor design, the baseline SPARC tokamak plasma discharge is evaluated for its expected H-mode access, pedestal pressure and edge-localized mode (ELM) characteristics. A clear window for H-mode access is predicted for full field DT plasmas, with the available 25 MW of design auxiliary power. Additional alpha heating is likely needed for H-mode sustainment. Pressure pedestal predictions in the developed H-mode are surveyed using the EPED model. The projected SPARC pedestal would be limited dominantly by peeling modes and may achieve pressures in excess of 0.3 MPa at a density of approximately 3 × 1020 m−3. High pedestal pressure is partially enabled by strong equilibrium shaping, which has been increased as part of recent design iterations. Edge-localized modes (ELMs) with >1 MJ of energy are projected, and approaches for reducing the ELM size, and thus the peak energy fluence to divertor surfaces, are under consideration. The high pedestal predicted for SPARC provides ample margin to satisfy its high fusion gain (Q) mission, so that even if ELM mitigation techniques result in a 2× reduction of the pedestal pressure, Q > 2 is still predicted.
This project will work closely with existing service partners involved in street level services and focus on testing and evaluating three approaches for street level interventions for youth who are homeless and who have severe or moderate mentally illness. Youth will be asked to choose their preferred service approach:
Housing First related initiatives focused on interventions designed to move youth to appropriate and available housing and ongoing housing supports.
Treatment First initiatives to provide Mental Health/Addiction supports and treatment solutions, and; Simultaneous attention to both Housing and Treatment Together
Our primary objective is to understand the service delivery preferences of homeless youth and understand the outcomes of these choices. Our research questions include:
1. Which approaches to service are chosen by youth?
2. What are the differences and similarities between groups choosing each approach?
3. What are the critical ingredients needed to effectively implement services for homeless youth from the perspectives of youth, families and service providers?
Focus groups with staff and family members will occur to assist in understanding the nature of each of service approach, changes that evolve within services, & facilitators and barriers to service delivery. This work will be important in determining which approach is chosen by youth and why. Evaluating the outcomes with each choice will provide valuable information about outcomes for the service options chosen by youth. This assist in better identifying weaknesses in the services offered and inform further development of treatment options that youth will accept.
We hypothesized an increase in dorsolateral prefrontal cortex (DLPFC) glutamate levels would occur after three weeks of repetitve transcranial magnetic stimulation (rTMS) treatment and a decrease in major depressive disorder (MDD) symptoms.
Method:
We report six cases (four females) 15–21 years of age with treatment-resistant MDD. Participants had a mean age of 18.7 years and a mean IQ of 102.3. Short echo proton magnetic resonance spectroscopy (H-MRS) was used to quantify glutamate levels in the left DLPFC (4.5cc) before and after rTMS treatment. rTMS was localized to the left DLPFC and applied for 15 consecutive weekdays. Treatment response was defined as a greater than 50% reduction in Hamilton Depression Rating Scale scores (Ham-D).1H-MRS data was analyzed with LCModel to determine glutamate concentration.
Results:
Following rTMS, treatment responders (N=4) showed an increase (relative to baseline) in left DLPFC glutamate levels (11%), which corresponded to an improvement in depressive symptom severity (68% Ham-D score reduction). Treatment non-responders (N=2) had elevated baseline glutamate levels compared to responders in that same region, which decreased with rTMS (−10%). Procedures were generally well tolerated with no adverse events.
Conclusions:
rTMS is feasible and possibly efficacious in adolescents with MDD. In responders, rTMS may act by Induced elevations in elevating DFPLC glutamate levels in the left DLPFC, thereby leading to symptom improvement. Transcranial Magnetic Stimulation for Adolescent Depression (TMSAD)
Observation of the ion source generated background has been an area of focus during our routine analytical work. It is noted that the results of very-low-ratio samples are dependent upon the particular procedures for measurement using the present-day Cs+ sputter ion sources. When measured without excessive Cs+ fluxes and without interleafing with other higher-ratio samples and references, the accelerator mass spectrometry (AMS) sensitivity can be somewhat improved. In some cases, it appears possible to assess old radiocarbon (14C) samples to beyond the long-standing 60 kyr limit. A number of observational studies are made for the sole purpose of minimizing the final contamination to the rare isotopes that is generated within the ion source.
Intrauterine growth restriction (IUGR) has adverse effects on metabolic health and early life, whereas physical activity is protective against later development of metabolic disease. Relationships between birth weight and physical activity in humans, and effects of IUGR on voluntary activity in rodents, are mixed and few studies have measured physical activity in a free-ranging environment. We hypothesized that induced restriction of placental growth and function (PR) in sheep would decrease spontaneous ambulatory activity (SAA) in free-ranging adolescent and young adult progeny from multi-fetal pregnancies. To test this hypothesis, we used Global Positioning System watches to continuously record SAA between 1800 and 1200 h the following day, twice during a 16-day recording period, in progeny of control (CON, n=5 males, 9 females) and PR pregnancies (n=9 males, 10 females) as adolescents (30 weeks) and as young adults (43 weeks). PR reduced size at birth overall, but not in survivors included in SAA studies. In adolescents, SAA did not differ between treatments and females were more active than males overall and during the day (each P<0.001). In adults, daytime SAA was greater in PR than CON females (P=0.020), with a similar trend in males (P=0.053) and was greater in females than males (P=0.016). Adult SAA was negatively correlated with birth weight in females only. Contrary to our hypothesis, restricted placental function and small size at birth did not reduce progeny SAA. The mechanisms for increased daytime SAA in adult female PR and low birth weight sheep require further investigation.
We present here the low-dispersion optical spectra of 295 QSO candidates. The great majority of the objects were originally selected as QSOs from the Parkes 2700 MHz radio survey, although we have also included spectra of several optically selected QSOs. A few of the QSO candidates are now better described as radio galaxies and BL Lac objects. This collection of spectra is not suitable for statistical studies unless due consideration is given to selection effects.
A recent outbreak of Q fever was linked to an intensive goat and sheep dairy farm in Victoria, Australia, 2012-2014. Seventeen employees and one family member were confirmed with Q fever over a 28-month period, including two culture-positive cases. The outbreak investigation and management involved a One Health approach with representation from human, animal, environmental and public health. Seroprevalence in non-pregnant milking goats was 15% [95% confidence interval (CI) 7–27]; active infection was confirmed by positive quantitative PCR on several animal specimens. Genotyping of Coxiella burnetii DNA obtained from goat and human specimens was identical by two typing methods. A number of farming practices probably contributed to the outbreak, with similar precipitating factors to the Netherlands outbreak, 2007-2012. Compared to workers in a high-efficiency particulate arrestance (HEPA) filtered factory, administrative staff in an unfiltered adjoining office and those regularly handling goats and kids had 5·49 (95% CI 1·29–23·4) and 5·65 (95% CI 1·09–29·3) times the risk of infection, respectively; suggesting factory workers were protected from windborne spread of organisms. Reduction in the incidence of human cases was achieved through an intensive human vaccination programme plus environmental and biosecurity interventions. Subsequent non-occupational acquisition of Q fever in the spouse of an employee, indicates that infection remains endemic in the goat herd, and remains a challenge to manage without source control.
Accumulating evidence links childhood adversity to negative health outcomes in adulthood. However, most of the available evidence is retrospective and subject to recall bias. Published reports have sometimes focused on specific childhood exposures (e.g. abuse) and/or specific outcomes (e.g. major depression). Other studies have linked childhood adversity to a large and diverse number of adult risk factors and health outcomes such as cardiovascular disease. To advance this literature, we undertook a broad examination of data from two linked surveys. The goal was to avoid retrospective distortion and to provide a descriptive overview of patterns of association.
Methods.
A baseline interview for the Canadian National Longitudinal Study of Children and Youth collected information about childhood adversities affecting children aged 0–11 in 1994. The sampling procedures employed in a subsequent study called the National Population Health Survey (NPHS) made it possible to link n = 1977 of these respondents to follow-up data collected later when respondents were between the ages of 14 and 27. Outcomes included major depressive episodes (MDE), some risk factors and educational attainment. Cross-tabulations were used to examine these associations and adjusted estimates were made using the regression models. As the NPHS was a longitudinal study with multiple interviews, for most analyses generalized estimating equations (GEE) were used. As there were multiple exposures and outcomes, a statistical procedure to control the false discovery rate (Benjamini–Hochberg) was employed.
Results.
Childhood adversities were consistently associated with a cluster of potentially related outcomes: MDE, psychotropic medication use and smoking. These outcomes may be related to one another since psychotropic medications are used in the treatment of major depression, and smoking is strongly associated with major depression. However, no consistent associations were observed for other outcomes examined: physical inactivity, excessive alcohol consumption, binge drinking or educational attainment.
Conclusions.
The conditions found to be the most strongly associated with childhood adversities were a cluster of outcomes that potentially share pathophysiological connections. Although prior literature has suggested that a very large number of adult outcomes, including physical inactivity and alcohol-related outcomes follow childhood adversity, this analysis suggests a degree of specificity with outcomes potentially related to depression. Some of the other reported adverse outcomes (e.g. those related to alcohol use, physical inactivity or more distal outcomes such as obesity and cardiovascular disease) may emerge later in life and in some cases may be secondary to depression, psychotropic medication use and smoking.
In the present study, we examined the association between maternal education and unhealthy eating behaviour (the consumption of snack and sugar-sweetened beverages (SSB)) and explored environmental factors that might mediate this association in 11-year-old children. These environmental factors include home availability of snacks and SSB, parental rules about snack and SSB consumption, parental intake of snacks and SSB, peer sensitivity and children's snack-purchasing behaviour. Data were obtained from the fourth wave of the INPACT (IVO Nutrition and Physical Activity Child cohorT) study (2011), in which 1318 parent–child dyads completed a questionnaire. Data were analysed using multivariate regression models. Children of mothers with an intermediate educational level were found to consume more snacks than those of mothers with a high educational level (B= 1·22, P= 0·02). This association was not mediated by environmental factors. Children of mothers with a low educational level were found to consume more SSB than those of mothers with a high educational level (B= 0·63, P< 0·01). The association between maternal educational level and children's SSB consumption was found to be mediated by parental intake of snacks and SSB and home availability of SSB. The home environment seems to be a promising setting for interventions on reducing socio-economic inequalities in children's SSB consumption.
Considerable evidence now links childhood adversity to a variety of adult health problems. Unfortunately, almost all of these studies have relied upon retrospective assessment of childhood events, creating a vulnerability to bias. In this study, we sought to examine three associations using data sources that allowed for both prospective and retrospective assessment of childhood events.
Methods.
Methods. A 1994 national survey of children between the ages of 0 and 11 collected data from a ‘person most knowledgeable’ (usually the mother) about a child. It was possible to link data for n = 1977 of these respondents to data collected from the same people in a subsequent adult study. The latter survey included retrospective reports of childhood adversity. We examined three adult health outcomes in relation to prospectively and retrospectively assessed childhood adversity: major depressive episodes, excessive alcohol consumption and painful conditions.
Results.
Results. A strong association between childhood adversities (as assessed by both retrospective and prospective methods) and major depression was identified although the association with retrospective assessment was stronger. Weaker associations were found for painful conditions, but these did not depend on the method of assessment. Associations were not found for excessive alcohol consumption irrespective of the method of assessment.
Conclusions.
These findings help to allay concerns that associations between childhood adversities and health outcomes during adulthood are merely artefacts of recall bias. In this study, retrospective and prospective assessment strategies produced similar results.
The application of metabolomics in multi-centre studies is increasing. The aim of the present study was to assess the effects of geographical location on the metabolic profiles of individuals with the metabolic syndrome. Blood and urine samples were collected from 219 adults from seven European centres participating in the LIPGENE project (Diet, genomics and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis). Nutrient intakes, BMI, waist:hip ratio, blood pressure, and plasma glucose, insulin and blood lipid levels were assessed. Plasma fatty acid levels and urine were assessed using a metabolomic technique. The separation of three European geographical groups (NW, northwest; NE, northeast; SW, southwest) was identified using partial least-squares discriminant analysis models for urine (R2X: 0·33, Q2: 0·39) and plasma fatty acid (R2X: 0·32, Q2: 0·60) data. The NW group was characterised by higher levels of urinary hippurate and N-methylnicotinate. The NE group was characterised by higher levels of urinary creatine and citrate and plasma EPA (20 : 5 n-3). The SW group was characterised by higher levels of urinary trimethylamine oxide and lower levels of plasma EPA. The indicators of metabolic health appeared to be consistent across the groups. The SW group had higher intakes of total fat and MUFA compared with both the NW and NE groups (P≤ 0·001). The NE group had higher intakes of fibre and n-3 and n-6 fatty acids compared with both the NW and SW groups (all P< 0·001). It is likely that differences in dietary intakes contributed to the separation of the three groups. Evaluation of geographical factors including diet should be considered in the interpretation of metabolomic data from multi-centre studies.