Homotaurine, a safe blood-brain barrier permeable GABAA-R-specific agonist, ameliorates disease in mouse models of multiple sclerosis.

There is a need for treatments that can safely promote regulatory lymphocyte responses. T cells express GABA receptors (GABAA-Rs) and GABA administration can inhibit Th1-mediated processes such as type 1 diabetes and rheumatoid arthritis in mouse models. Whether GABAA-R agonists can also inhibit Th17-driven processes such as experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), is an open question. GABA does not pass through the blood-brain barrier (BBB) making it ill-suited to inhibit the spreading of autoreactivity within the CNS. Homotaurine is a BBB-permeable amino acid that antagonizes amyloid fibril formation and was found to be safe but ineffective in long-term Alzheimer's disease clinical trials. Homotaurine also acts as GABAA-R agonist with better pharmacokinetics than that of GABA. Working with both monophasic and relapsing-remitting mouse models of EAE, we show that oral administration of homotaurine can (1) enhance CD8+CD122+PD-1+ and CD4+Foxp3+ Treg, but not Breg, responses, (2) inhibit autoreactive Th17 and Th1 responses, and (3) effectively ameliorate ongoing disease. These observations demonstrate the potential of BBB-permeable GABAA-R agonists as a new class of treatment to enhance CD8+ and CD4+ Treg responses and limit Th17 and Th1-medaited inflammation in the CNS

A novel homozygous SLC2A9 mutation associated with renal-induced hypouricemia

Hereditary renal hypouricemia (RHUC) is a genetically heterogenous disorder characterized by defective uric acid (UA) reabsorption resulting in hypouricemia and increased fractional excretion of UA; acute kidney injury (AKI) and nephrolithiasis are recognized complications. Type 1 (RHUC1) is caused by mutations in the SLC22A12 gene, whereas RHUC2 is caused by mutations in the SLC2A9 gene. Patient ethnicity is diverse but only few Caucasian families with an SLC2A9 mutation have been reported. The current report describes the clinical history, biochemical and molecular genetics findings of a native Austrian family with RHUC2. The propositus presented with 2 episodes of exercise-induced AKI and exhibited profound hypouricemia. Mutational screening of the SLC22A12 and SLC2A9 genes was performed. The molecular analyses revealed the homozygous c.512G>A transition that leads to the p.Arg171His missense substitution in SLC2A9, confirming the diagnosis of RHUC2. Segregation study of the causal mutation revealed that the mother and elder sister were heterozygous carriers, whereas the younger sister was found to be homozygous. We report the identification of a novel mutation in SLC2A9 as the cause of RHUC2 in a native Austrian family. We show that glucose transporter 9 mutations cause severe hypouricemia in homozygous individuals and confirm the high risk of AKI in male individuals harbouring these mutations. In our literature review, we provide an overview of the putative underlying pathophysiology, potential renal complications, findings on kidney biopsy as well as potential long-time renal sequela

Altitude Investigation of Performance of Turbine-propeller Engine and Its Components

An investigation was conducted on a turbine-propeller engine in the NACA Lewis altitude wind tunnel at altitudes from 5000 to 35,000 feet. The applicability of generalized parameters to turbine-propeller engine data, analyses of the compressor, the combustion chambers, and the turbine, and a study of the over-all engine performance are reported. Engine performance data obtained at sea-level static conditions could be used to predict static performance at altitudes up to 35,000 feet by use of the standard generalized parameters

PREDICTORS OF AVERAGE WAIT TIME AT AN INTERSECTION USING ARTIFICIAL NEURAL NETWORK

This paper reports the results of the studies on identifying the predictors of average wait times of vehicles at intersections. The strength and direction of the relationship of these predictors were gauged from the values and sign of the predictor. Simulated data obtained using a JavaScript algorithm were used. The variables tested for predictability included the traffic light time (seconds), traffic density per minute, number of input tracks (1 or 2), and number of output tacks (1 or 2). The program can then simulate the average wait time in seconds for an intersection (down, right, up, and left). The programme simulated the average wait times for the four directions of traffic flows at the intersection. These data were used in an artificial neural network algorithm. About 70% of the data were used for training and the remaining 30% were used for testing. The ANN model used is called a multi-layer perceptron (MLP). All the 4 models developed have one input layer, one hidden layer, and one output layer. The results indicated that density as the strongest predictor accounting for 100% importance among the variables tested. In some situations, traffic light times or the number of input or output tracks in some directions could also predict wait times to a lesser extent. Density was positively related to the wait times. These findings have been largely supported by the published literature when linked to traffic flow and travel times

DATA MANAGEMENT IN INDUSTRIAL COMPANIES: THE CASE OF AUSTRIA

Data has become the most critical asset that companies have. Companies often lack the experience to generate the highest possible value from their data. Most current studies on this topic were not restricted to the participants' geographical location or industrial sector. The originality of this research is that a survey is sent to industrial companies in Austria solely. This article intends to answer the following research question: 'What is the current state regarding data management in Austrian industrial companies? It should start a discussion in the community if Austrian and European companies are behind their international competitors in company-wide data management. It should also give an overview of standardized KPIs, responsibilities, problems, data storage technology, and decision-making. While most industrial companies in Austria stated that their KPIs are standardized within the company and strategic decisions are based on data, Austrian companies lack behind their international competitors in terms of C-level positions for data management and a company-wide data management strategy

Patients with Cancer and Family Caregivers: Management of symptoms caused by Cancer or Cancer Therapy at Home

People are diagnosed with cancer sooner nowadays thanks to increased awareness and improvements in cancer screenings. Patients are able to live longer due to cancer treatment regimens; however, they suffer the consequences of living with cancer and therapy-related symptoms. Symptom management is challenging for both patients and family caregivers. Therefore, family members must be integrated in the patient’s care plan. For this review, a literature search was conducted to determine what types of interventions were available that involved family members of cancer patients with the management of cancer and therapy-related symptoms. The following interventions were found that were designed for the family caregivers or both the patient and caregiver to aide with symptom management: pain intervention program, massage therapy, telephone intervention, self-efficacy improvement, coping enhancement and a multidimensional intervention. A positive effect was noted in all the studies, but several had no significance in the patient intervention group but did in the caregiver intervention group. However, studies indicated decreased symptom intensity for various symptoms, decreased symptom distress for both the patient and caregiver, increased self-efficacy of the family member, and increased satisfaction with certain interventions. Further research should be conducted on both existing interventions to better determine their effect and on family symptom management of cancer patients as they need support from healthcare professionals as well

Monitoring body temperature during moderate intensity exercise and inactive recovery in the cold: a pilot study

Exposure to cold ambient conditions during outdoor recreation can lead to significant heat loss. It is unknown how fast body temperature decreases or how fast a person could become hypothermic in cold temperatures. We present a series of pilot tests involving moderate intensity exercise and inactive recovery in the cold to monitor how body temperature changes with exposure to -10°C. The primary aim of this pilot study was to test the feasibility of the proposed protocol with the intention to design a main study. The primary questions were: (i) to what degree does body temperature increase or decrease with this protocol, (ii) whether epitympanic temperature is a suitable measure of core temperature using a recently developed, non-invasive device and (iii) if participants are able to tolerate the cold during inactive recovery. This pilot series included seven participants. After an acclimatization phase (15 minutes), participants exercised at 60% peak heart rate (20 minutes) followed by a seated, inactive recovery phase (15 minutes) in the cold. The mean ambient conditions were -10.0±0.4°C and 66.1±8.6% relative humidity and no wind. The primary findings based on the feasibility criteria were that body temperature increased while exercising at an intensity of 60% HRpeak and decreased during inactive recovery by -0.3±0.1°C (epitympanic temperature). Secondly, the agreement between epitympanic and esophageal temperature (mean difference 0.2°C, 95% confidence interval -0.5 to 0.0, p=0.095) was better than in previous studies. Finally, all participants were able to tolerate the cold and complete the study despite thermal discomfort and shivering in the recovery phase. This protocol was successful in showing small changes in body temperature during exercise and recovery in the cold, though some modifications to the current protocol are recommended to elicit a larger effect size

Preliminary Altitude Operational Characteristics of a J57-P1 Turbojet Engine

The operational characteristics of a J57-P1 turbojet engine have been investigated at altitudes between 15,000 and 66,000 feet in the Lewis altitude wind tunnel. Included in this study is a discussion of fuel nozzle coking, the altitude operating limits with and without the standard engine control, the compressor surge characteristics, and the engine starting and windmilling characteristics. Severe circumferential turbine outlet temperature gradients which occurred at high altitude as a result of fuel nozzle coking were alleviated by the manufacturer's change in the fuel flow divider schedule and in a nozzle gasket material. Compressor air bleed is required to prevent surge of the outboard compressor in the low engine speed region. The maximum altitude at which the engine was operated without the control was about 66,000 feet at 0.8 flight Mach number and at a reduced engine speed to avoid compressor surge; with the engine control in operation, the altitude operating limit is reduced to approximately 59,000 feet. The maximum altitude at which the engine was started was about 40,000 feet