ML-Based Analysis of Particle Distributions in High-Intensity Laser Experiments: Role of Binning Strategy.

When entering the phase of big data processing and statistical inferences in experimental physics, the efficient use of machine learning methods may require optimal data preprocessing methods and, in particular, optimal balance between details and noise. In experimental studies of strong-field quantum electrodynamics with intense lasers, this balance concerns data binning for the observed distributions of particles and photons. Here we analyze the aspect of binning with respect to different machine learning methods (Support Vector Machine (SVM), Gradient Boosting Trees (GBT), Fully-Connected Neural Network (FCNN), Convolutional Neural Network (CNN)) using numerical simulations that mimic expected properties of upcoming experiments. We see that binning can crucially affect the performance of SVM and GBT, and, to a less extent, FCNN and CNN. This can be interpreted as the latter methods being able to effectively learn the optimal binning, discarding unnecessary information. Nevertheless, given limited training sets, the results indicate that the efficiency can be increased by optimizing the binning scale along with other hyperparameters. We present specific measurements of accuracy that can be useful for planning of experiments in the specified research area.

Characteristics and microgeographic variation of whistles from the vocal repertoire of beluga whales (Delphinapterus leucas) from the White Sea.

The beluga whale (Delphinapterus leucas) produces a variety of sounds, including whistles as well as pulsed, noisy, and biphonic vocalizations. This study presents the fine-scale, microgeographic characteristics of beluga whistles from data collected in four locations across Onega Bay and Dvina Bay in the White Sea, Russia. Ten parameters were measured from 1232 whistles. The whistles had a fundamental frequency from 0.4 to 25.0 kHz and duration from 0.04 to 3.93 s. Although two distinct types could be recognized in the White Sea beluga's whistle repertoire, other whistles formed a graded continuum. Among them, "flat" whistle contours with no inflection points appear to be the most common (39.7%), to be followed by frequency-modulated whistles: ascending (27.1%) and descending (15.6%). Non-linear phenomena detected in the whistles included frequency jumps (23.1%), biphonations (13.2%), sidebands (5.2%), and subharmonics (0.5%). The whistles varied in frequency parameters and duration across the locations, while those recorded in the same location in different years showed minimal difference. Beluga whistles appear to be an extremely diverse class of vocalizations. This, together with the lack of clear correlations between the behavior of whales and whistle production suggests whistles may perform multiple functions within the beluga whale communication system.

A beluga whale socialized with bottlenose dolphins imitates their whistles.

The research on imitation in the animal kingdom has more than a century-long history. A specific kind of imitation, auditory-vocal imitation, is well known in birds, especially among songbirds and parrots, but data for mammals are limited to elephants, marine mammals, and humans. Cetaceans are reported to imitate various signals, including species-specific calls, artificial sounds, and even vocalizations from other species if they share the same habitat. Here we describe the changes in the vocal repertoire of a beluga whale that was housed with a group of bottlenose dolphins. Two months after the beluga's introduction into a new facility, we found that it began to imitate whistles of the dolphins, whereas one type of its own calls seemed to disappear. The case reported here may be considered as an interesting phenomenon of vocal accommodation to new social companions and cross-species socialization in cetaceans.

Development of Human Hair Reference Material Supporting the Biomonitoring of Methylmercury.

A certified reference material, NIMD-01, was developed for the analysis of mercury speciation in human hair. We collected the hair of Vietnamese males from a barbershop in Hanoi in 2016 and prepared 1200 bottles containing 3 g of sieved and blended hair powder. The certified value was given on a dry-mass basis, with the moisture content obtained by drying at 85°C for 4 h. Certified values with the expanded uncertainties (coverage factor, k = 2) were as follows: methylmercury, 0.634 ± 0.071 mg kg-1 as mercury; total mercury, 0.794 ± 0.050 mg kg-1; copper, 12.8 ± 1.4 mg kg-1; zinc, 234 ± 29 mg kg-1; selenium, 1.52 ± 0.29 mg kg-1. An indicative arsenic concentration of 0.17 ± 0.03 mg kg-1 was measured. Extended uncertainties were estimated by sample homogeneity, long- and short-term stabilities, and a characterization from measurements made by collaborating laboratories.

New insights and long-term safety of tocilizumab in rheumatoid arthritis.

Rheumatoid arthritis is a leading musculoskeletal cause of disability in Western society. Therapeutic options have expanded rapidly with the advent of biological agents as treatment options. One of these, tocilizumab, targets the interleukin-6 receptor and has been approved since the late 2000s in many jurisdictions. This approval was based on 6-12 month trials. It is now appropriate to look at longer-term studies and what new insights they have provided into this agent. Data are based largely on observational studies with their well-known limitations as well as some further randomized trials and provide a number of important observations regarding both efficacy and safety. In conclusion, the longer-term data suggest tocilizumab efficacy increases over time for both signs and symptoms and radiographic change. It is also corticosteroid sparing. The safety data are consistent with the shorter-term trials and are largely reassuring but some questions still remain over cardiovascular safety and cancer risk.

Guideline development for the management of gout: role of combination therapy with a focus on lesinurad.

The aim of this review was to summarize the evidence for combination therapy to achieve serum urate (SUA) target levels in gout. Within this overarching aim, a second aim was to evaluate the evidence for a new uricosuric agent lesinurad, which inhibits urate transport in the kidney. In summary, this review indicates that there are a number of ways to approach patients who do not achieve a target serum urate with allopurinol (APL) monotherapy. These include higher doses of APL up to 600-800 mg/d, switching to febuxostat, or adding in a uricosuric. For the latter option, controlled supporting evidence is available for benzbromarone, probenecid, and lesinurad. All options appear similar in terms of success rates, so the choice of option comes down to physician and patient choice, cost, experience, and strength of the evidence base. Increasing the dose of APL is the cheapest option, while febuxostat is consistently superior to standard doses of APL. The strongest evidence for the uricosuric option is available for lesinurad as trials of other agents are either nonexistent or based on small single-centre trials. It is suggested that guidelines should be expanded to consider all of these evidence-based options in the not-uncommon occurrence of APL inadequate response.

Benefit-risk assessment of diacerein in the treatment of osteoarthritis.

Osteoarthritis (OA) is the leading musculoskeletal cause of disability. Despite this, there is no consensus on the precise definition of OA and what is the best treatment to improve symptoms and slow disease progression. Current pharmacological treatments include analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX) inhibitors. None of those treatments are disease-modifying agents that target the core pathological processes in OA. Diacerein, a semi-synthetic anthraquinone derivative, inhibits the interleukin-1-beta (IL-1ß) cytokine which, according to animal studies, plays a key role in the pathogenesis of OA. Diacerein was synthesized in 1980 and licensed in some European Union and Asian countries for up to 20 years. It has shown modest efficacy and acceptable tolerability in a number of trials of low to moderate quality. Early this year, the European Medicines Agency (EMA) conducted a review and restricted the use of diacerein-containing medicines. This was because of major concerns about the frequency and severity of diarrhoea and liver disorders in OA patients. In addition, the EMA's Pharmacovigilance Risk Assessment Committee (PRAC) questioned the limited clinical benefits of diacerein, which, in their view, did not outweigh its risks. The aim of this review is to provide a benefit-risk assessment of diacerein in the treatment of OA, based on asystematic evaluation of the published efficacy and safety data. Overall, there is evidence that diacerein is modestly effective for symptoms and possibly for radiographic changes, but this needs to be balanced against higher rates of gastrointestinal toxicity.