The IceCube Neutrino Observatory, located under 1.4 km of Antarctic ice, instruments a cubic kilometer of ice with 5,160 optical modules that detect Cherenkov radiation originating from neutrino ...interactions. The more densely instrumented center, DeepCore, aims to detect atmospheric neutrinos at 10 GeV scales to improve important measurements of fundamental neutrino properties such as the oscillation parameters and to search for non-standard interactions. Sensitivity to oscillation parameters, dependent on the distance traveled over the neutrino energy (L/E), is limited in IceCube by the resolution of the arrival angle (which determines L) and energy (E). Event reconstruction improvements can therefore directly lead to advancements in oscillation results. This work uses a Convolutional Neural Network (CNN) to reconstruct the energy of 10 GeV scale neutrino events in IceCube, providing results with competitive resolutions and faster runtimes than previous likelihood-based methods.
A large number of studies have reported on spontaneous viral clearance rates in acute hepatitis C infection, however most have been small, and reported rates have varied quite widely. To improve the ...precision of the estimated rate of spontaneous viral clearance, a systematic review was conducted of longitudinal studies. Factors associated with viral clearance were also examined. Inclusion criteria for studies were: longitudinal assessment from time of acute hepatitis C; hepatitis C virus RNA analysis as determinant of viral clearance; untreated for acute hepatitis C. Information on study population, and factors that may influence viral clearance were extracted from each study. Viral clearance was defined among individuals with at least 6 months follow‐up following acute hepatitis C. The number of subjects with viral clearance was expressed as a proportion for each study and a weighted mean for proportion was calculated. A total of 31 studies were examined. Study populations included nine studies of post‐transfusion hepatitis, 19 of acute clinical hepatitis, and three of sero‐incident cases. In total, data was available for 675 subjects and the mean study population was 22 (range 4–67). The proportion with viral clearance ranged from 0.0 to 0.8, with a weighted mean of 0.26 (95% CI 0.22–0.29). Factors associated with viral clearance were female gender and acute clinical hepatitis C study population. Further studies are required to more clearly define predictors of clearance and guide therapeutic intervention strategies.
Among antibiotics, Central Nervous System (CNS) adverse drug reactions (ADRs) are often under-suspected and overlooked. Cephalosporins are an important cause of drug-induced CNS ADRs but the ...characteristics of such ADR have not been fully explored. We aimed to characterize the profile of cephalosporins serious CNS ADRs.
We performed an analysis of serious reports recorded in the French Pharmacovigilance database from 1987 to 2017.
A total of 511 serious ADRs reports was analyzed. Patients had a mean age of 67.1 years and were mainly men (52.5%), with a mean creatinine clearance of 32.9 ml/min. The most involved molecules were cefepime (33.1%), ceftriaxone (29.7%), ceftazidime (19.6%), cefotaxime (9%) and cefazoline (2.9%), mostly administered intravenously (87.3%). A CNS history was observed in 25% of the reports (n = 128). Patients exhibited encephalopathy (30.3%), confusional state (19.4%), convulsion (15.1%), myoclonia (9.4%), status epilepticus (9.2%), coma (6.3%) and hallucination (4.3%). The mean time of onset was 7.7 days and the mean duration was 6 days. Cephalosporin plasma levels were recorded for 153 patients (29.9%) and 107 were above the standards including 62 (57.9%) related to renal impairment. Electroencephalograms were performed in 38.2% (n = 195) of the patients and 81% (n = 158) were abnormal.
This study characterizes an off-target CNS ADRs of several cephalosporins. Ceftriaxone represented a large part of our reports after cefepime and it would be relevant to warn healthcare professionals. Investigations (EEG, though plasma levels and renal function) can be precious tools for clinicians to make a prompt diagnosis and improve patients' outcomes.
•Central nervous system adverse effects provided by cephalosporins are under-suspected and can lead to death.•Central nervous system adverse effects can be neurologic and psychiatric.•Ceftriaxone is widely represented with several deaths, an awareness should be important for clinicians.
To examine the time course of alteration in neural process (spinal loop properties) during prolonged tennis playing, 12 competitive players performed a series of neuromuscular tests every 30 min ...during a 3‐h match protocol. Muscle activation (twitch interpolation) and normalized EMG activity were assessed during maximal voluntary contraction (MVC) of plantar flexors. Spinal reflexes and M‐waves were evoked at rest (i.e., Hmax and Mmax, respectively) and during MVC (i.e., Hsup, V‐wave, Msup, respectively). MVC torque declined significantly (P<0.001) across the match protocol, due to decrease (P<0.001) in muscle activation and in normalized EMG activity. The impairment in MVC was significantly correlated (r=0.77; P<0.05) with the decline in muscle activation. Hmax/Mmax (P<0.001), Hsup/Msup (P<0.01) and V/Msup (P<0.05) ratios were depressed with fatigue and decreased by ∼80%, 46% and 61% at the end of exercise, respectively. Simultaneously, peak twitch torque and M‐wave amplitude were significantly (P<0.01) altered with exercise, suggesting peripheral alterations. During prolonged tennis playing, the compromised voluntary strength capacity is linked to a reduced neural input to the working muscles. This central activation deficit partly results from a modulation in spinal loop properties.
Évaluer les effets d’une préparation physique proprioceptive sur l’équilibre statique et dynamique du véliplanchiste.
Le protocole expérimental était composé de 11 sujets de haut niveau qui ont été ...partagés en deux groupes (GP=6 et GT=5), un groupe proprioception (GP) effectuant une préparation physique proprioceptive sur surface instable et un groupe témoin (GT) conservant une préparation physique « classique ». La période d’expérimentation a duré six semaines et l’équilibre a été évalué de deux façons en pré- et post-entraînement : équilibre statique à l’aide d’une plateforme de force et équilibre dynamique à l’aide d’un accéléromètre.
À l’issue du protocole, seul GP a amélioré significativement son équilibre statique en appui unipodal et son équilibre dynamique. Il en ressort qu’un entraînement proprioceptif décontextualisé améliore significativement la perception de l’équilibre en planche à voile olympique. Ces résultats suggèrent la prise en compte de l’importance de développer les habiletés perceptives dans une pratique telle que la voile.
Evaluation of the effects of a physical and proprioceptive training on the static and dynamic balance in Olympic windsurfers.
The experimental protocol consisted of 11 high level participants who were divided into two groups (PG=6 and TG=5), a proprioception group (PG) performing a proprioceptive conditioning on an unstable surface and a control group (TG) using a traditional conditioning. The period of experimentation lasted 6 weeks and balance was evaluated before and after training with two different tests: static balance on a force platform and dynamic balance with an accelerometer.
At the end of the protocol only the PG significantly improved their static balance in the unipodal position, as well as their dynamic balance.
It can be concluded that unspecific proprioceptive training significantly improves the perception of balance in Olympic windsurfers. These results revealed that the importance of developing these perceptual skills in a sport such as sailing should be taken into account.
Summary
Background
Inhibitors of dipeptidyl peptidase (DPP)‐IV have been suspected in the onset of bullous pemphigoid for several years now. However, comparative studies assessing the link between ...DPP‐IV inhibitor exposure and bullous pemphigoid have not yet been performed.
Objectives
To detect, from the French Pharmacovigilance Database (FPVD), a signal of risk of bullous pemphigoid during DPP‐IV inhibitor exposure by comparative study.
Methods
All spontaneous reports of DPP‐IV inhibitor‐related bullous pemphigoid recorded in the FPVD between April 2008 and August 2014 were described. We conducted disproportionality analyses (case–noncase method) to assess the link between DPP‐IV inhibitors and bullous pemphigoid, calculating reporting odds ratios (RORs). We also compared DPP‐IV inhibitor‐induced bullous pemphigoid reports rated per million defined daily doses dispensed during the study period.
Results
Among 217 331 spontaneous adverse drug reaction reports registered in the FPVD, 1297 involved DPP‐IV inhibitors. Among these observations, 42 were bullous pemphigoid (vildagliptin, n = 31; sitagliptin, n = 10; saxagliptin, n = 1). The ROR for pooled DPP‐IV inhibitors was 67·5 95% confidence interval (CI) 47·1–96·9. Disproportionality was also observed for each DPP‐IV inhibitor: vildagliptin (ROR 225·3, 95% CI 148·9–340·9), sitagliptin (ROR 17·0, 95% CI 8·9–32·5) and saxagliptin (ROR 16·5, 95% CI 2·3–119·1). Analyses adjusted on dispensing data led to similar results.
Conclusions
These data confirm a strong signal for an increased risk of bullous pemphigoid during DPP‐IV inhibitor exposure. This adverse drug reaction is observed for each DPP‐IV inhibitor, suggesting a class effect. The signal was higher with vildagliptin than with the other DPP‐IV inhibitors.
What's already known about this topic?
Implication of dipeptidyl peptidase (DPP)‐IV inhibitors in bullous pemphigoid occurrence has been suggested in several case reports.
What does this study add?
There is a significant signal for an increased risk of bullous pemphigoid during DPP‐IV inhibitor exposure.
This signal is outlined for each DPP‐IV inhibitor, suggesting a class effect.
The signal of risk of bullous pemphigoid is higher with vildagliptin than with other DPP‐IV inhibitors.
Research into the biomechanical manifestation of fatigue during exhaustive runs is increasingly popular but additional understanding of the adaptation of the spring-mass behaviour during the course ...of strenuous, self-paced exercises continues to be a challenge in order to develop optimized training and injury prevention programs. This study investigated continuous changes in running mechanics and spring-mass behaviour during a 5-km run. 12 competitive triathletes performed a 5-km running time trial (mean performance: ̴17 min 30 s) on a 200 m indoor track. Vertical and anterior-posterior ground reaction forces were measured every 200 m by a 5-m long force platform system, and used to determine spring-mass model characteristics. After a fast start, running velocity progressively decreased (- 11.6%; P<0.001) in the middle part of the race before an end spurt in the final 400-600 m. Stride length (- 7.4%; P<0.001) and frequency (- 4.1%; P=0.001) decreased over the 25 laps, while contact time (+ 8.9%; P<0.001) and total stride duration (+ 4.1%; P<0.001) progressively lengthened. Peak vertical forces (- 2.0%; P<0.01) and leg compression (- 4.3%; P<0.05), but not centre of mass vertical displacement (+ 3.2%; P>0.05), decreased with time. As a result, vertical stiffness decreased (- 6.0%; P<0.001) during the run, whereas leg stiffness changes were not significant (+ 1.3%; P>0.05). Spring-mass behaviour progressively changes during a 5-km time trial towards deteriorated vertical stiffness, which alters impact and force production characteristics.
The aim of this study was to characterize the effect of a 5 km running time trial on the neuromuscular properties of the plantar flexors. Eleven well-trained triathletes performed a series of ...neuromuscular tests before and immediately after the run on a 200 m indoor track. Muscle activation (twitch interpolation) and normalized EMG activity were assessed during maximal voluntary contraction (MVC) of plantar flexors. Maximal
soleus
H-reflexes and M-waves were evoked at rest (i.e.
H
MAX
and
M
MAX
, respectively) and during MVC (i.e.
H
SUP
and
M
SUP
, respectively). MVC significantly declined (−27%;
P
< 0.001) after the run, due to decrease in muscle activation (−8%;
P
< 0.05) and
M
MAX
-normalized EMG activity (−13%;
P
< 0.05). Significant reductions in M-wave amplitudes (
M
MAX
: −13% and
M
SUP
: −16%;
P
< 0.05) as well as
H
MAX
/
M
MAX
(−37%;
P
< 0.01) and
H
SUP
/
M
SUP
(−25%;
P
< 0.05) ratios occurred with fatigue. Following exercise, the single twitch was characterized by lower peak torque (−16%;
P
< 0.001) as well as shorter contraction (−19%;
P
< 0.001) and half-relaxation (−24%;
P
< 0.001) times. In conclusion, the reduction in plantar flexors strength induced by a 5 km running time trial is caused by peripheral adjustments, which are attributable to a failure of the neuromuscular transmission and excitation–contraction coupling. Fatigue also decreased the magnitude of efferent motor outflow from spinal motor neurons to the plantar flexors and part of this suboptimal neural drive is the result of an inhibition of
soleus
motoneuron pool reflex excitability.
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