Quantitative Gait and Balance Outcomes for Ataxia Trials: Consensus Recommendations by the Ataxia Global Initiative Working Group on Digital-Motor Biomarkers

\ua9 2023, The Author(s).With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid, finely granulated, digital health measures are highly warranted to augment clinical and patient-reported outcome measures. Gait and balance disturbances most often present as the first signs of degenerative cerebellar ataxia and are the most reported disabling features in disease progression. Thus, digital gait and balance measures constitute promising and relevant performance outcomes for clinical trials. This narrative review with embedded consensus will describe evidence for the sensitivity of digital gait and balance measures for evaluating ataxia severity and progression, propose a consensus protocol for establishing gait and balance metrics in natural history studies and clinical trials, and discuss relevant issues for their use as performance outcomes

Quantitative gait and balance outcomes for ataxia trials: consensus recommendations by the Ataxia Global Initiative Working Group on Digital-Motor Biomarkers

With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid, finely granulated, digital health measures are highly warranted to augment clinical and patient-reported outcome measures. Gait and balance disturbances most often present as the first signs of degenerative cerebellar ataxia and are the most reported disabling features in disease progression. Thus, digital gait and balance measures constitute promising and relevant performance outcomes for clinical trials.This narrative review with embedded consensus will describe evidence for the sensitivity of digital gait and balance measures for evaluating ataxia severity and progression, propose a consensus protocol for establishing gait and balance metrics in natural history studies and clinical trials, and discuss relevant issues for their use as performance outcomes

An overview of burst, buckling, durability and corrosion analysis of lightweight FRP composite pipes and their applicability

© 2019 Elsevier Ltd. All rights reserved.The main aim of this review article was to address the performance of filament wound fibre reinforced polymer (FRP) composite pipes and their critical properties, such as burst, buckling, durability and corrosion. The importance of process parameters concerning merits and demerits of the manufacturing methods was discussed for the better-quality performance. Burst analysis revealed that the winding angle of ±55° was observed to be optimum with minimum failure mechanisms, such as matrix cracking, whitening, leakage and fracture. The reduction of buckling effect was reported in case of lower hoop stress value in the hoop to axial stress ratio against axial, compression and torsion. A significant improvement in energy absorption was observed in the hybrid composite pipes with the effect of thermal treatment. However, the varying winding angle in FRP pipe fabrication was reported as an influencing factor affecting all the aforementioned properties. Almost 90% of the reviewed studies was done using E-glass/epoxy materials for the composite pipe production. By overcoming associated limitations, such as replacing synthetic materials, designing new material combinations and cost-benefit analysis, the production cost of the lightweight FRP composite pipes can be decreased for the real-time applications.Peer reviewe

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Management of late anemia in Rhesus hemolytic disease: Use of recombinant human erythropoietin (A pilot study)

The management of (Rhesus) hemolytic disease of the fetus and newborn includes intrauterine transfusions to prevent the development of hydrops, treatment of the possible hyperbilirubinemia in the immediate postnatal period, and treatment of late anemia. Low levels of serum erythropoietin due to suppression of the bone marrow by multiple intrauterine transfusions is a suggested mechanism for this anemia. The aim of our study was to test whether recombinant human erythropoietin reduced the need for erythrocyte transfusions in these infants. Twenty infants with Rhesus isoimmunization were blindly randomized to treatment and control groups at the 2nd wk of life. The number of intrauterine and exchange transfusions and demographic data were similar in both groups. The infants in the treatment group received recombinant human erythropoietin, s.c. 200 U/kg of body weight three times a week for a period of 6 wk, whereas the infants in the control group received a placebo for the same period. In the treatment group, the mean number of erythrocyte transfusions was significantly lower than that of the control group (1.8 versus 4.2). The reticulocyte counts and Hb levels rose earlier in the treatment group. The platelet and neutrophil counts were similar in both groups throughout the study. This study demonstrates that recombinant human erythropoietin treatment decreases the need for erythrocyte transfusions in the late anemia of infants with Rh isoimmunization. Considering the risks of blood transfusions, this decrease in the donor exposure is worthwhile

Effects of recombinant human erythropoietin in infants with very low birth weights

Anaemia of prematurity, a postnatal fall in haemoglobin concentration and haematocrit, is particularly common in those born at less than 32 weeks of gestation. Experimental and clinical data implicate inadequate erythropoietin production as an important reason. In this study recombinant human erythropoietin (r-HuEpo) was used in an attempt to treat or prevent this anaemia and thereby provide an alternative to erythrocyte transfusions. Premature infants (birth weight less than or equal to 1250 g and gestational age less than or equal to 32 weeks), who were likely to need transfusions, were randomly assigned to receive 4 weeks of treatment with either subcutaneously administered r-HuEpo (200 U; n = 12) or placebo (n = 12), three times weekly. All patients had oral supplements of elemental iron at a dose of 3 mg/kg/day. Treatment was started in the third week of life. Reticulocyte counts were significantly raised (P < 0.05) in the group treated with r-HuEpo at the end of treatment. The neonates in the group treated with r-HuEpo needed fewer erythrocyte transfusions than those in the placebo group during treatment. There were no toxic effects attributable to r-HuEpo. The results indicate that treatment of infants with very low birth weights with r-HuEpo will reduce their need for erythrocyte transfusions

Neonatal septicemia in a neonatal intensive care unit - Results of four years

The outcome of congenital and nosocomial septicemia has been documented in infants who were admitted to a neonatal intensive care unit over a four-year period. The overall incidence of neonatal septicemia in the neonatal intensive care unit was 5.4 percent. Common causes of neonatal septicemia were gram-negative bacilli and staphylococci. Gram-positive microorganisms were the major causative agents for early-onset septicemia. Since the most common pathogen in cases of nosocomial sepsis was gram-negative bacillus, higher mortality rates were observed in nosocomial sepsis. The overall mortality rate in neonatal sepsis was 44.2 percent. The mortality rate in infants in whom nosocomial septicemia developed was significantly higher than in the infants in whom early-onset septicemia developed. However, as gram-negative colonization of the nursery recently changed to gram-positive microorganisms, the mortality rate is hoped to decrease

HIGH-DOSE INTRAVENOUS IMMUNOGLOBULIN THERAPY FOR RHESUS HEMOLYTIC-DISEASE

Rhesus haemolytic disease is a continuing problem in the newborn especially in countries where the use of anti-D immunoglobulin is not prevalent. The fetuses may need intrauterine transfusions to prevent hydrops faetalis and they also may need exchange transfusions to treat the hyperbilirubinaemia that develops after birth. These interventions expose the baby to several blood donors, hence the risk of infection and exchange transfusions, This study was performed to test whether the use of high-dose intravenous immunoglobulin soon after the birth of these infants reduced the need for exchange transfusions. After randomization, intravenous immunoglobulin was given at a dose of 500 mg/kg to 22 infants in the treatment group. Nothing was given to the 19 controls. The number of exchange transfusions needed decreased significantly in the treatment group. No side-effects of intravenous immunoglobulins were seen

Isoniazid and hypoglycaemia in a premature infant

Severe hypoglycaemia requiring more than 20 mg/kg per minute glucose infusion was seen in a premature infant. The infant was born to a woman with active tuberculosis, and she was on prophylactic isoniazid. Discontinuation of isoniazid resulted in prompt recovery of hypoglycaemia. Further pharmacological studies may be needed to establish a cause and effect relationship