Reinforced metallic composites Patent

High strength reinforced metallic composites for applications over wide temperature rang

Weight Gain Is Associated with Medial Contact Site of Subthalamic Stimulation in Parkinson's Disease

The aim of our study was to assess changes in body-weight in relation to active electrode contact position in the subthalamic nucleus. Regular body weight measurements were done in 20 patients with advanced Parkinson's disease within a period of 18 months after implantation. T1-weighted (1.5T) magnetic resonance images were used to determine electrode position in the subthalamic nucleus and the Unified Parkinson's disease rating scale (UPDRS-III) was used for motor assessment. The distance of the contacts from the wall of the third ventricle in the mediolateral direction inversely correlated with weight gain (r = −0.55, p<0.01) and with neurostimulation-related motor condition expressed as the contralateral hemi-body UPDRS-III (r = −0.42, p<0.01). Patients with at least one contact within 9.3 mm of the wall experienced significantly greater weight gain (9.4±(SD)4.4 kg, N = 11) than those with both contacts located laterally (3.9±2.7 kg, N = 9) (p<0.001). The position of the active contact is critical not only for motor outcome but is also associated with weight gain, suggesting a regional effect of subthalamic stimulation on adjacent structures involved in the central regulation of energy balance, food intake or reward

Protocols for calibrating multibeam sonar

Author Posting. © Acoustical Society of America, 2005. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 117 (2005): 2013-2027, doi:10.1121/1.1869073.Development of protocols for calibrating multibeam sonar by means of the standard-target method is documented. Particular systems used in the development work included three that provide the water-column signals, namely the SIMRAD SM2000/90- and 200-kHz sonars and RESON SeaBat 8101 sonar, with operating frequency of 240 kHz. Two facilities were instrumented specifically for the work: a sea well at the Woods Hole Oceanographic Institution and a large, indoor freshwater tank at the University of New Hampshire. Methods for measuring the transfer characteristics of each sonar, with transducers attached, are described and illustrated with measurement results. The principal results, however, are the protocols themselves. These are elaborated for positioning the target, choosing the receiver gain function, quantifying the system stability, mapping the directionality in the plane of the receiving array and in the plane normal to the central axis, measuring the directionality of individual beams, and measuring the nearfield response. General preparations for calibrating multibeam sonars and a method for measuring the receiver response electronically are outlined. Advantages of multibeam sonar calibration and outstanding problems, such as that of validation of the performance of multibeam sonars as configured for use, are mentioned.Support by the National Science Foundation through Award No. OCE-0002664, NOAA through Grant No. NA97OG0241, and the Cooperative Institute for Climate and Ocean Research (CICOR) through NOAA Contract No. NA17RJ1223 is acknowledged

Dystonia in neurodegeneration with brain iron accumulation: outcome of bilateral pallidal stimulation

Neurodegeneration with brain iron accumulation encompasses a heterogeneous group of rare neurodegenerative disorders that are characterized by iron accumulation in the brain. Severe generalized dystonia is frequently a prominent symptom and can be very disabling, causing gait impairment, difficulty with speech and swallowing, pain and respiratory distress. Several case reports and one case series have been published concerning therapeutic outcome of pallidal deep brain stimulation in dystonia caused by neurodegeneration with brain iron degeneration, reporting mostly favourable outcomes. However, with case studies, there may be a reporting bias towards favourable outcome. Thus, we undertook this multi-centre retrospective study to gather worldwide experiences with bilateral pallidal deep brain stimulation in patients with neurodegeneration with brain iron accumulation. A total of 16 centres contributed 23 patients with confirmed neurodegeneration with brain iron accumulation and bilateral pallidal deep brain stimulation. Patient details including gender, age at onset, age at operation, genetic status, magnetic resonance imaging status, history and clinical findings were requested. Data on severity of dystonia (Burke Fahn Marsden Dystonia Rating Scale—Motor Scale, Barry Albright Dystonia Scale), disability (Burke Fahn Marsden Dystonia Rating Scale—Disability Scale), quality of life (subjective global rating from 1 to 10 obtained retrospectively from patient and caregiver) as well as data on supportive therapy, concurrent pharmacotherapy, stimulation settings, adverse events and side effects were collected. Data were collected once preoperatively and at 2–6 and 9–15 months postoperatively. The primary outcome measure was change in severity of dystonia. The mean improvement in severity of dystonia was 28.5% at 2–6 months and 25.7% at 9–15 months. At 9–15 months postoperatively, 66.7% of patients showed an improvement of 20% or more in severity of dystonia, and 31.3% showed an improvement of 20% or more in disability. Global quality of life ratings showed a median improvement of 83.3% at 9–15 months. Severity of dystonia preoperatively and disease duration predicted improvement in severity of dystonia at 2–6 months; this failed to reach significance at 9–15 months. The study confirms that dystonia in neurodegeneration with brain iron accumulation improves with bilateral pallidal deep brain stimulation, although this improvement is not as great as the benefit reported in patients with primary generalized dystonias or some other secondary dystonias. The patients with more severe dystonia seem to benefit more. A well-controlled, multi-centre prospective study is necessary to enable evidence-based therapeutic decisions and better predict therapeutic outcomes

Pathogenic <i>SPTBN1</i> variants cause an autosomal dominant neurodevelopmental syndrome

SPTBN1 encodes βII-spectrin, the ubiquitously expressed β-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal βII-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of βII-spectrin in the central nervous system

Genetic Determinants of Time Perception Mediated by the Serotonergic System

Background: The present study investigates neurobiological underpinnings of individual differences in time perception. Methodology: Forty-four right-handed Russian Caucasian males (18–35 years old) participated in the experiment. The polymorphism of the genes related to the activity of serotonin (5-HT) and dopamine (DA)-systems (such as 5-HTT, 5HT2a, MAOA, DAT, DRD2, COMT) was determined upon the basis of DNA analysis according to a standard procedure. Time perception in the supra-second range (mean duration 4.8 s) was studied, using the duration discrimination task and parametric fitting of psychometric functions, resulting in individual determination of the point of subjective equality (PSE). Assuming the ‘dual klepsydra model ’ of internal duration representation, the PSE values were transformed into equivalent values of the parameter k (kappa), which is a measure of the ‘loss rate ’ of the duration representation. An association between time representation parameters (PSE and k, respectively) and 5-HT-related genes was found, but not with DArelated genes. Higher ‘loss rate ’ (k) of the cumulative duration representation were found for the carriers of genotypes characterized by higher 5-HT transmission, i.e., 1) lower 5-HT reuptake, known for the 5-HTTLPR SS polymorphism compared with LL, 2) lower 5-HT degradation, described for the ‘low expression ’ variant of MAOA VNTR gene compared with ‘high expression ’ variant, and 3) higher 5-HT2a receptor density, proposed for the TT polymorphism of 5-HT2a T102C gene compared with CC

Loss-of-Function Variants in HOPS Complex Genes VPS16 and VPS41 Cause Early Onset Dystonia Associated with Lysosomal Abnormalities.

OBJECTIVES: The majority of people with suspected genetic dystonia remain undiagnosed after maximal investigation, implying that a number of causative genes have not yet been recognized. We aimed to investigate this paucity of diagnoses. METHODS: We undertook weighted burden analysis of whole-exome sequencing (WES) data from 138 individuals with unresolved generalized dystonia of suspected genetic etiology, followed by additional case-finding from international databases, first for the gene implicated by the burden analysis (VPS16), and then for other functionally related genes. Electron microscopy was performed on patient-derived cells. RESULTS: Analysis revealed a significant burden for VPS16 (Fisher's exact test p value, 6.9 × 109 ). VPS16 encodes a subunit of the homotypic fusion and vacuole protein sorting (HOPS) complex, which plays a key role in autophagosome-lysosome fusion. A total of 18 individuals harboring heterozygous loss-of-function VPS16 variants, and one with a microdeletion, were identified. These individuals experienced early onset progressive dystonia with predominant cervical, bulbar, orofacial, and upper limb involvement. Some patients had a more complex phenotype with additional neuropsychiatric and/or developmental comorbidities. We also identified biallelic loss-of-function variants in VPS41, another HOPS-complex encoding gene, in an individual with infantile-onset generalized dystonia. Electron microscopy of patient-derived lymphocytes and fibroblasts from both patients with VPS16 and VPS41 showed vacuolar abnormalities suggestive of impaired lysosomal function. INTERPRETATION: Our study strongly supports a role for HOPS complex dysfunction in the pathogenesis of dystonia, although variants in different subunits display different phenotypic and inheritance characteristics. ANN NEUROL 2020;88:867-877

Twenty important research questions in microbial exposure and social equity

Social and political policy, human activities, and environmental change affect the ways in which microbial communities assemble and interact with people. These factors determine how different social groups are exposed to beneficial and/or harmful microorganisms, meaning microbial exposure has an important socioecological justice context. Therefore, greater consideration of microbial exposure and social equity in research, planning, and policy is imperative. Here, we identify 20 research questions considered fundamentally important to promoting equitable exposure to beneficial microorganisms, along with safeguarding resilient societies and ecosystems. The 20 research questions we identified span seven broad themes, including the following: (i) sociocultural interactions; (ii) Indigenous community health and well-being; (iii) humans, urban ecosystems, and environmental processes; (iv) human psychology and mental health; (v) microbiomes and infectious diseases; (vi) human health and food security; and (vii) microbiome-related planning, policy, and outreach. Our goal was to summarize this growing field and to stimulate impactful research avenues while providing focus for funders and policymakers

Correlation between Early Season Insecticide Control of Pink Bollworm and Other Pests and Subsequent Whitefly Applications near Gila Bend, AZ, 1997

Cotton pesticide application histories in the Gila Basin were followed from 27 April through 20 September. The main interest was the effect of early season applications to control pink bollworm, Pectinophora gossypiella, and other pests on subsequent whitefly applications. Categories explored include, transgenic and non transgenic cotton, planting dates, and location within the valley. Regression analysis shows a significant effect due to the early season control for either P. gossypiella, or other pests (P > 0.009) but lower for them together (P > 0.026). Early applications for either PBW or other pest resulted in increased application for whitefly