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Nonsuicidal self-injury (NSSI) is a common but poorly understood phenomenon in adolescents. This study examined the Sustained Threat domain in female adolescents with a continuum of NSSI severity (N = 142). Across NSSI lifetime frequency and NSSI severity groups (No + Mild NSSI, Moderate NSSI, Severe NSSI), we examined physiological, self-reported and observed stress during the Trier Social Stress Test; amygdala volume; amygdala responses to threat stimuli; and resting-state functional connectivity (RSFC) between amygdala and medial prefrontal cortex (mPFC). Severe NSSI showed a blunted pattern of cortisol response, despite elevated reported and observed stress during TSST. Severe NSSI showed lower amygdala–mPFC RSFC; follow-up analyses suggested that this was more pronounced in those with a history of suicide attempt for both moderate and severe NSSI. Moderate NSSI showed elevated right amygdala activation to threat; multiple regressions showed that, when considered together with low amygdala–mPFC RSFC, higher right but lower left amygdala activation predicted NSSI severity. Patterns of interrelationships among Sustained Threat measures varied substantially across NSSI severity groups, and further by suicide attempt history. Study limitations include the cross-sectional design, missing data, and sampling biases. Our findings highlight the value of multilevel approaches in understanding the complexity of neurobiological mechanisms in adolescent NSSI.
The Old Copper Complex (OCC) refers to the production of heavy copper-tool technology by Archaic Native American societies in the Lake Superior region. To better define the timing of the OCC, we evaluated 53 (eight new and 45 published) radiocarbon (14C) dates associated with copper artifacts and mines. We compared these dates to six lake sediment-based chronologies of copper mining and annealing in the Michigan Copper District. 14C dates grouped by archaeological context show that cremation remains, and wood and cordage embedded in copper artifacts have ages that overlap with the timing of high lead (Pb) concentrations in lake sediment. In contrast, dates in stratigraphic association and from mines are younger than those from embedded and cremation materials, suggesting that the former groups reflect the timing of processes that occurred post-abandonment. The comparatively young dates obtained from copper mines therefore likely reflect abandonment and infill of the mines rather than active use. Excluding three anomalously young samples, the ages of embedded organic material associated with 15 OCC copper artifacts range from 8500 to 3580 cal BP, confirming that the OCC is among the oldest known metalworking societies in the world.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Most measures of anxious avoidance are limited to disorder-specific mechanisms and ignore the measurement of courage/approach responding in confronting fearful situations.
The purpose of the present study was to construct and validate a self-report assessment of the tendency towards avoidant or approach responding in fearful situations, the Response to Fearful Situations Scale (RFSS).
Method and Results:
In Study 1 (n = 241), exploratory factor analysis resulted in two factors, avoidance and approach. Study 2 (n = 423) replicated the two-factor structure and established test–re-test reliability. In Study 3 (n = 44), the RFSS demonstrated predictive validity on a behavioural avoidance task. In Studies 4 (n = 253) and 5 (n = 256), the RFSS was associated with clinical symptoms above existing measures of avoidance.
These results validate the use of the RFSS as a transdiagnostic measure of avoidance and approach.
It is important to be able to compare and evaluate different solutions early in development. This paper proposes a method for structuring historical data into a data model that can support the evaluation of new design concepts. The data is contextualized by linking it to a hierarchical decomposition of existing products. Two case studies were conducted to evaluate the value of using historical data when evaluating new concepts. The cases confirm that the proposed method is useful for evaluation of new concepts.
Treatment of alcohol addiction remains challenging, since only half of all patients achieve long-term abstinence by currently available therapies.
In the last 2 years, there have been promising reports on deep brain stimulation (DBS) of NAc in addiction (animal models, one case report of a patient with severe anxiety disorder and secondary addiction). Our group treated 5 patients with treatment resistant alcohol addiction with DBS so far. Our initial data of the first 3 patients has just been published. However, these very positive results arise from a continuous open stimulation and have not been placebo controlled.
To assess the impact of discontinuation of bilateral DBS of the NAc on craving for alcohol in patients whose addiction remitted after initiation of DBS.
Crossover, double-blinded phase of 2 × 4 weeks with sham-stimulation in one and stimulation in the other 4 weeks.
Until now, one patient finished the 8 weeks of study (remaining patients will finish experiment in December 2009). In this patient, stimulation was continued in the first and stopped in the latter 4 weeks. While he experienced no changes or side effects in the first part, he showed a massive craving for alcohol one day after discontinuation, which again remitted when the experiment was stopped and the stimulator was turned on again after 3 days.
DBS of NAc seems to selectively alleviate craving for alcohol thus enabling patients to remain abstinent. These results justify clinical studies in larger samples of patients with treatment resistant alcohol addiction.
Neuroendocrine changes of the stress hormone system and REM sleep abnormalities are potential vulnerability markers for depression. Investigating underlying genetics provides new insights into the molecular pathways of these endophenotypes and into the pathophysiology of depression vulnerability. We selected a high-risk linkage and endophenotype approach, i.e., we investigated REM sleep abnormalities (REM density) and altered stress hormone regulation (dex/CRH test) in families with a high prevalence of major depression.
Eleven families were so far included, comprising 82 high risk family members. 32 of them were unaffected, 33 remitted, and 17 suffered from an affective disorder at the time of the investigation. Illumina Infinium Whole Genome genotyping with 100k bead chips was performed. Variance component (VC), and a quantitative trait linkage analysis (QTL) on polysomnographic (REM density) and neuroendocrine vulnerability markers (dex/CRH test) were applied.
Linkage analysis (VC, QTL) revealed suggestive linkage (LOD score > 2) for altered REM density at loci of the chromosomes 2, 4, 8 and X. The linkage results on chromosomes 2 and X correspond to previous findings. No results were obtained with a classical diagnosis based linkage approach.
The use of quantitative vulnerability markers in a high risk family study and a SNP based whole genome approach revealed a number of loci with suggestive linkage, that were not detectable with the classical linkage approach. Our findings suggest the suitability of investigating vulnerability marker in combination with a SNP based whole genome approach in complex disorders like depression.
Community-based breeding programs (CBBPs) for small ruminants have been suggested as alternatives to centralised, government-controlled breeding schemes which have been implemented in many developing countries. An innovative methodological framework on how to design, implement and sustain CBBPs was tested in three sites in Ethiopia: Bonga, Horro and Menz. In these CBBPs, the main selection trait identified through participatory approaches was 6-month weight in all three sites. In Horro and Bonga, where resources such as feed and water permitted larger litter sizes, twinning rate was included. Ten-year (2009 to 2018) performance data from the breeding programs were analysed using Average Information Restricted Maximum Likelihood method (AI-REML). Additionally, the socioeconomic impact of CBBPs was assessed. Results indicated that 6-month weight increased over the years in all breeds. In Bonga, the average increase was 0.21 ± 0.018 kg/year, followed by 0.18 ± 0.007 and 0.11 ± 0.003 kg/year in Horro and Menz, respectively. This was quite substantial in an on-farm situation. The birth weight of lambs did not improve over the years in Bonga and Horro sheep but significant increases occurred in Menz. Considering that there was no direct selection on birth weight in the community flock, the increased weights observed in Menz could be due to correlated responses, but this was not the case in Bonga and Horro. The genetic trend for prolificacy over the years in both Bonga and Horro flocks was positive and significant (P < 0.01). This increase in litter size, combined with the increased 6-month body weight, increased income by 20% and farm-level meat consumption from slaughter of one sheep per year to three. The results show that CBBPs are technically feasible, result in measurable genetic gains in performance traits and impact the livelihoods of farmers.
AFM-based nanoelectrical modes have numerous
applications in fields ranging from semiconductors
to biology. The data produced have traditionally
been in the form of a 2D map, generated in contact
mode, with a single electrical data point per
XY location. Electrical ramps
or spectra would be generated at a few, carefully
selected locations. This article discusses a new
approach to nanoelectrical imaging that creates an
electrical data cube and a correlated nanomechanical
data cube while operating at normal imaging speeds.
This approach avoids contact mode imaging, thus
extending electrical measurements to soft and
fragile samples and improving measurement
consistency. Moreover, this is a general approach
that is applicable to most nanoelectrical modes and
The pathophysiological mechanisms underlying the seasonal dynamic and epidemic occurrence of bacterial meningitis in the African meningitis belt remain unknown. Regular seasonality (seasonal hyperendemicity) is observed for both meningococcal and pneumococcal meningitis and understanding this is critical for better prevention and modelling. The two principal hypotheses for hyperendemicity during the dry season imply (1) an increased risk of invasive disease given asymptomatic carriage of meningococci and pneumococci; or (2) an increased transmission of these bacteria from carriers and ill individuals. In this study, we formulated three compartmental deterministic models of seasonal hyperendemicity, featuring one (model1-‘inv’ or model2-‘transm’), or a combination (model3-‘inv-transm’) of the two hypotheses. We parameterised the models based on current knowledge on meningococcal and pneumococcal biology and pathophysiology. We compared the three models' performance in reproducing weekly incidences of suspected cases of acute bacterial meningitis reported by health centres in Burkina Faso during 2004–2010, through the meningitis surveillance system. The three models performed well (coefficient of determination R2, 0.72, 0.86 and 0.87, respectively). Model2-‘transm’ and model3-‘inv-transm’ better captured the amplitude of the seasonal incidence. However, model2-‘transm’ required a higher constant invasion rate for a similar average baseline transmission rate. The results suggest that a combination of seasonal changes of the risk of invasive disease and carriage transmission is involved in the hyperendemic seasonality of bacterial meningitis in the African meningitis belt. Consequently, both interventions reducing the risk of nasopharyngeal invasion and the bacteria transmission, especially during the dry season are believed to be needed to limit the recurrent seasonality of bacterial meningitis in the meningitis belt.
Knowledge of the effects of burial depth and burial duration on seed viability and, consequently, seedbank persistence of Palmer amaranth (Amaranthus palmeri S. Watson) and waterhemp [Amaranthus tuberculatus (Moq.) J. D. Sauer] ecotypes can be used for the development of efficient weed management programs. This is of particular interest, given the great fecundity of both species and, consequently, their high seedbank replenishment potential. Seeds of both species collected from five different locations across the United States were investigated in seven states (sites) with different soil and climatic conditions. Seeds were placed at two depths (0 and 15 cm) for 3 yr. Each year, seeds were retrieved, and seed damage (shrunken, malformed, or broken) plus losses (deteriorated and futile germination) and viability were evaluated. Greater seed damage plus loss averaged across seed origin, burial depth, and year was recorded for lots tested at Illinois (51.3% and 51.8%) followed by Tennessee (40.5% and 45.1%) and Missouri (39.2% and 42%) for A. palmeri and A. tuberculatus, respectively. The site differences for seed persistence were probably due to higher volumetric water content at these sites. Rates of seed demise were directly proportional to burial depth (α=0.001), whereas the percentage of viable seeds recovered after 36 mo on the soil surface ranged from 4.1% to 4.3% compared with 5% to 5.3% at the 15-cm depth for A. palmeri and A. tuberculatus, respectively. Seed viability loss was greater in the seeds placed on the soil surface compared with the buried seeds. The greatest influences on seed viability were burial conditions and time and site-specific soil conditions, more so than geographical location. Thus, management of these weed species should focus on reducing seed shattering, enhancing seed removal from the soil surface, or adjusting tillage systems.
Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.
Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.
HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.
Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.
Mild behavioral impairment (MBI) describes later life acquired, sustained neuropsychiatric symptoms (NPS) in cognitively normal individuals or those with mild cognitive impairment (MCI), as an at-risk state for incident cognitive decline and dementia. We developed an operational definition of MBI and tested whether the presence of MBI was related to caregiver burden in patients with subjective cognitive decline (SCD) or MCI assessed at a memory clinic.
MBI was assessed in 282 consecutive memory clinic patients with SCD (n = 119) or MCI (n = 163) in accordance with the International Society to Advance Alzheimer's Research and Treatment – Alzheimer's Association (ISTAART–AA) research diagnostic criteria. We operationalized a definition of MBI using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Caregiver burden was assessed using the Zarit caregiver burden scale. Generalized linear regression was used to model the effect of MBI domains on caregiver burden.
While MBI was more prevalent in MCI (85.3%) than in SCD (76.5%), this difference was not statistically significant (p = 0.06). Prevalence estimates across MBI domains were affective dysregulation (77.8%); impulse control (64.4%); decreased motivation (51.7%); social inappropriateness (27.8%); and abnormal perception or thought content (8.7%). Affective dysregulation (p = 0.03) and decreased motivation (p=0.01) were more prevalent in MCI than SCD patients. Caregiver burden was 3.35 times higher when MBI was present after controlling for age, education, sex, and MCI (p < 0.0001).
MBI was common in memory clinic patients without dementia and was associated with greater caregiver burden. These data show that MBI is a common and clinically relevant syndrome.
As a result of the selection for genotypes with greater sow prolificacy, litter size increased and, concomitantly, average litter birth weight and early postnatal survival rates of low birth weight (L-BtW) offspring decreased. This study compared the impact of l-carnitine (CAR) and l-arginine (ARG) supplemented with a milk replacer and fed to L-BtW piglets born from large litters from days 7 to 28 of age on growth performance, carcass composition, organ and Semitendinosus muscle (STM) development. A total of 30 female and castrated Swiss Large White piglets weaned at 7 days of age were assigned to three milk replacer diets containing either no supplement (CON), CAR (0.40 g/piglet per day) or ARG (1.08 g/kg BW per day). Piglets were kept in pairs in rescue decks (0.54 m2). They were weighed daily and daily allowance of both, feed and ARG, was adjusted accordingly. Thus, feed allowance depended on growth. Each day, the milk replacer was prepared with water (1:4). Feed (allowance: 60 g dry matter/kg BW per day) was offered daily in six equal rations. Feed intake and feed efficiency was assessed for the pairs and apparent total tract-energy and -protein digestibility was determined from days 21 to 28 of age. On day 28, piglets were euthanized, blood samples were collected and the whole STM and organs were weighed. In STM, the size and metabolic properties of myofibers were determined. No difference in growth performance was found between dietary treatments, but piglets from the CAR group tended (P<0.10) to grow faster during the 1st experimental week and consume more feed from days 14 to 21 as compared with piglets of the CON group. A setback in growth in the last week in the CAR group coincided with the lower (P<0.05) energy and protein digestibility. Dietary treatments had no effect on STM and organ weight and myofiber size. Compared with the other groups, there were trends (P<0.10) for blood serum urea and glucose level to be greater in CAR and for non-esterified fatty acid level to be greater in ARG piglets. The greater (P<0.05) ratio of lactate dehydrogenase to either citrate synthase or β-hydroxyacyl-CoA dehydrogenase indicated that the relative importance of the glycolytic compared with the oxidative pathway was greater in STM of CAR and ARG compared with CON piglets. These results suggest that ARG and CAR supplements were beneficial for muscle maturation whereas findings on phenotypic traits were rather unsystematic.
Synthetic rubbers, synthetic plastic polymers (polyvinyl chlorides [PVC]), polyurethane blends, and polyethylene blends make up modern-day agricultural spray hoses. The objective of this study was to determine whether agricultural hose types would differ with respect to 3,6-dichloro-2-methoxybenzoic acid (dicamba) sequestration. Field and greenhouse studies were conducted to evaluate the sequestration potential of dicamba within five agricultural hose types when cleaned with different cleanout procedures. Rinsate solutions were applied to soybean, which was used as a bio-indicator to test for cleanout efficiency. Differences among hose types and cleanout procedures exist with observations including soybean injury, height reduction, dry matter, yield, and part per million by volume (ppmv) analyte retained. The makeup of PVC polyurethane-blend and synthetic rubber–blend hoses increased retention of dicamba analyte when compared with the polyethylene blend hose. No differences were observed after the addition of ammonia to the cleanout solution when compared with water alone. Differences in a hose type’s ability to sequester the dicamba analyte may have more to do with the hose’s internal chemical composition, manufacturing process, and composition breakdown. Scanning electron microscopy revealed imperfections in new PVC polyurethane and synthetic rubber hoses that eventually lead to inner wall depletion of these hose types. This is in contrast to what was found in the polyethylene-blend hose type, in which the inner wall is smooth and free of imperfections.
Streptococcus pneumoniae (Spn) is a leading cause of community-acquired pneumonia (CAP), yet existing diagnostic tools remain inadequate. We aimed to evaluate laboratory and radiological methods for detecting pneumococcal aetiology in CAP patients and to estimate Spn prevalence in this group. All-aged patients hospitalized with clinically defined CAP in northern Togo were enrolled during 2010–2013. Latent class analysis pooled results of semi-automated blood culture (SABC), whole blood lytA real-time polymerase chain reaction (rt-PCR), serum C-reactive protein (CRP), and chest radiography (CXR) and categorized patients as likely pneumococcal or non-pneumococcal CAP. We enrolled 1684 patients; 1501 had results for all tests. CXR, SABC, lytA rt-PCR and CRP >71·2 mg/l had sensitivities of 94% [95% confidence interval (CI) 87–100], 13% (95% CI 10–16), 17% (95% CI 14–21) and 78% (95% CI 75–80), and specificities of 88% (95% CI 84–93), 100% (95% CI 99–100), 97% (95% CI 96–99) and 77% (95% CI 75–79), respectively. Pneumococcal attributable proportion was 34% (95% CI 32–37), increasing with age and in men. We estimated that Spn caused one third of CAP. Whole blood lytA rt-PCR was more sensitive than SABC; both had low sensitivity and high specificity. Conversely CXR was highly sensitive and reasonably specific; it could be a useful tool for epidemiological studies aiming to define Spn pneumonia incidence across all ages.