Automated extraction of speech and turn-taking parameters in autism allows for diagnostic classification using a multivariable prediction model.

Autism spectrum disorder (ASD) is diagnosed on the basis of speech and communication differences, amongst other symptoms. Since conversations are essential for building connections with others, it is important to understand the exact nature of differences between autistic and non-autistic verbal behaviour and evaluate the potential of these differences for diagnostics. In this study, we recorded dyadic conversations and used automated extraction of speech and interactional turn-taking features of 54 non-autistic and 26 autistic participants. The extracted speech and turn-taking parameters showed high potential as a diagnostic marker. A linear support vector machine was able to predict the dyad type with 76.2% balanced accuracy (sensitivity: 73.8%, specificity: 78.6%), suggesting that digitally assisted diagnostics could significantly enhance the current clinical diagnostic process due to their objectivity and scalability. In group comparisons on the individual and dyadic level, we found that autistic interaction partners talked slower and in a more monotonous manner than non-autistic interaction partners and that mixed dyads consisting of an autistic and a non-autistic participant had increased periods of silence, and the intensity, i.e. loudness, of their speech was more synchronous.

The role of interpersonal synchrony in forming impressions of autistic and non-autistic adults.

When people meet, they almost instantaneously form an impression of each other. First impressions of character traits and rapport are less favourable when people with autism spectrum condition (ASC) are judged compared to non-autistic people. Little is known about the behavioural differences that drive these altered impressions. In the present study, we investigated the influence of interpersonal synchrony on impression formation of autistic and non-autistic people. Specifically, we used lagged cross-correlations to assess how much each interactant's motion energy, a measure which can be determined from video recordings, influenced the other interactant's motion energy. In short, silent clips of dyadic conversations, we asked non-autistic participants to rate their impression of one of the two interactants, which was solely based on the outlines of both interactants. We expected that the amount of leading of the target interactant, their diagnostic status as well as the interaction of these factors would influence impression formation. We found that while the amount of leading had a positive effect on the impressions of non-autistic interactants, this was not true for interactants with ASC. This suggests that interpersonal synchrony of motion energy is one driver of less favourable impressions of autistic compared to non-autistic people.

Thoracic sarcopenia as a predictive factor of SARS-COV2 evolution.

PURPOSE: Evaluation of CT sarcopenia as a predictor of intensive care hospitalization during SARS-COV2 infection. MATERIALS AND METHODS: Single-center retrospective study of patients admitted to hospital with SARS-COV2 infection. The estimation of muscle mass (skeletal muscle index (SMI)) for sarcopenia, measurement of muscle density for muscle quality and body adiposity, were based on CT views on the T4 and L3 levels measured at admission. Demographic data, percentage of pulmonary parenchymal involvement as well as the orientation of patients during hospitalization and the risk of hospitalization in intensive care were collected. RESULTS: A total of 162 patients hospitalized for SARS-COV2 infection were included (92 men and 70 women, with an average age of 64.6 years and an average BMI of 27.4). The muscle area measured at the level of L3 was significantly associated with the patient's unfavorable evolution (124.4cm2 [97; 147] vs 141.5 cm2 [108; 173]) (p = 0.007), as was a lowered SMI (p < 0.001) and the muscle area measured in T4 (OR = 0.98 [0.97; 0.99]), (p = 0.026). Finally, an abdominal visceral fat area measured at the level of L3 was also associated with a risk of hospitalization in intensive care (249.4cm2 [173; 313] vs 147.5cm2 [93.1; 228] (p < 0.001). CONCLUSION: This study demonstrates that thoracic and abdominal sarcopenia are independently associated with an increased risk of hospitalization in an intensive care unit, suggesting the need to assess sarcopenia on admission during SARS-COV2 infection.

Post-recombination effects in confined gases photoionized at megahertz repetition rates.

Recombination-driven acoustic pulses and heating in a photoionized gas transiently alter its refractive index. Slow thermal dissipation can cause substantial heat accumulation and impair the performance and stability of gas-based laser systems operating at strong-field intensities and megahertz repetition rates. Here we study this effect by probing the pulse-by-pulse buildup of refractive index changes in gases spatially confined inside a capillary. A high-power repetition-rate-tunable femtosecond laser photoionizes the gas at its free-space focus, while a transverse-propagating probe laser interferometrically monitors the resulting time-dependent changes in refractive index. The system allows convenient exploration of the nonlinear regimes used to temporally compress pulses with durations in the ∼30 to ∼300 fs range. We observe thermal gas-density depressions, milliseconds in duration, that saturate to a level that depends on the peak intensity and repetition rate of the pulses, in good agreement with numerical modelling. The dynamics are independently confirmed by measuring the mean speed-of-sound across the capillary core, allowing us to infer that the temperature in the gas can exceed 1000 K. Finally, we explore several strategies for mitigating these effects and improving the stability of gas-based high-power laser systems at high repetition rates.

Evaluation of immunologic parameters in canine glioma patients treated with an oncolytic herpes virus.

Aim: To molecularly characterize the tumor microenvironment and evaluate immunologic parameters in canine glioma patients before and after treatment with oncolytic human IL-12-expressing herpes simplex virus (M032) and in treatment naïve canine gliomas. Methods: We assessed pet dogs with sporadically occurring gliomas enrolled in Stage 1 of a veterinary clinical trial that was designed to establish the safety of intratumoral oncoviral therapy with M032, a genetically modified oncolytic herpes simplex virus. Specimens from dogs in the trial and dogs not enrolled in the trial were evaluated with immunohistochemistry, NanoString, Luminex cytokine profiling, and multi-parameter flow cytometry. Results: Treatment-naive canine glioma microenvironment had enrichment of Iba1 positive macrophages and minimal numbers of T and B cells, consistent with previous studies identifying these tumors as immunologically "cold". NanoString mRNA profiling revealed enrichment for tumor intrinsic pathways consistent with suppression of tumor-specific immunity and support of tumor progression. Oncolytic viral treatment induced an intratumoral mRNA transcription signature of tumor-specific immune responses in 83% (5/6) of canine glioma patients. Changes included mRNA signatures corresponding with interferon signaling, lymphoid and myeloid cell activation, recruitment, and T and B cell immunity. Multiplexed protein analysis identified a subset of oligodendroglioma subjects with increased concentrations of IL-2, IL-7, IL-6, IL-10, IL-15, TNFα, GM-CSF between 14 and 28 days after treatment, with evidence of CD4+ T cell activation and modulation of IL-4 and IFNγ production in CD4+ and CD8+ T cells isolated from peripheral blood. Conclusion: These findings indicate that M032 modulates the tumor-immune microenvironment in the canine glioma model.

Efficient single-cycle pulse compression of an ytterbium fiber laser at 10†MHz repetition rate.

Over the past years, ultrafast lasers with average powers in the 100 W range have become a mature technology, with a multitude of applications in science and technology. Nonlinear temporal compression of these lasers to few- or even single-cycle duration is often essential, yet still hard to achieve, in particular at high repetition rates. Here we report a two-stage system for compressing pulses from a 1030 nm ytterbium fiber laser to single-cycle durations with 5 µJ output pulse energy at 9.6 MHz repetition rate. In the first stage, the laser pulses are compressed from 340 to 25 fs by spectral broadening in a krypton-filled single-ring photonic crystal fiber (SR-PCF), subsequent phase compensation being achieved with chirped mirrors. In the second stage, the pulses are further compressed to single-cycle duration by soliton-effect self-compression in a neon-filled SR-PCF. We estimate a pulse duration of ∼3.4 fs at the fiber output by numerically back-propagating the measured pulses. Finally, we directly measured a pulse duration of 3.8 fs (1.25 optical cycles) after compensating (using chirped mirrors) the dispersion introduced by the optical elements after the fiber, more than 50% of the total pulse energy being in the main peak. The system can produce compressed pulses with peak powers >0.6 GW and a total transmission exceeding 66%.

Spatio-temporal measurement of ionization-induced modal index changes in gas-filled PCF by prism-assisted side-coupling.

We report the use of prism-assisted side-coupling to investigate the spatio-temporal dynamics of photoionization in an Ar-filled hollow-core photonic crystal fiber. By launching four different LP core modes we are able to probe temporal and spatial changes in the modal refractive index on timescales from a few hundred picoseconds to several hundred microseconds after the ionization event. We experimentally analyze the underlying gas density waves and find good agreement with quantitative and qualitative hydrodynamic predictions. Moreover, we observe periodic modulations in the MHz-range lasting for a few microseconds, indicating nanometer-scale vibrations of the fiber structure, driven by gas density waves.

Correction: Two stable variants of Burkholderia pseudomallei strain MSHR5848 express broadly divergent in vitro phenotypes associated with their virulence differences.

[This corrects the article DOI: 10.1371/journal.pone.0171363.].

Draft Genome Sequences of Eight Crimean-Congo Hemorrhagic Fever Virus Strains.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a geographically widespread RNA virus with a high degree of genomic diversity that complicates sequence-based diagnostics. Here, we sequenced eight CCHFV strains for improved assay design and deposition into FDA-ARGOS, the FDA's pathogen database for development and verification of next generation sequencing assays.

Two stable variants of Burkholderia pseudomallei strain MSHR5848 express broadly divergent in vitro phenotypes associated with their virulence differences.

Burkholderia pseudomallei (Bp), the agent of melioidosis, causes disease ranging from acute and rapidly fatal to protracted and chronic. Bp is highly infectious by aerosol, can cause severe disease with nonspecific symptoms, and is naturally resistant to multiple antibiotics. However, no vaccine exists. Unlike many Bp strains, which exhibit random variability in traits such as colony morphology, Bp strain MSHR5848 exhibited two distinct and relatively stable colony morphologies on sheep blood agar plates: a smooth, glossy, pale yellow colony and a flat, rough, white colony. Passage of the two variants, designated "Smooth" and "Rough", under standard laboratory conditions produced cultures composed of > 99.9% of the single corresponding type; however, both could switch to the other type at different frequencies when incubated in certain nutritionally stringent or stressful growth conditions. These MSHR5848 derivatives were extensively characterized to identify variant-associated differences. Microscopic and colony morphology differences on six differential media were observed and only the Rough variant metabolized sugars in selective agar. Antimicrobial susceptibilities and lipopolysaccharide (LPS) features were characterized and phenotype microarray profiles revealed distinct metabolic and susceptibility disparities between the variants. Results using the phenotype microarray system narrowed the 1,920 substrates to a subset which differentiated the two variants. Smooth grew more rapidly in vitro than Rough, yet the latter exhibited a nearly 10-fold lower lethal dose for mice than Smooth. Finally, the Smooth variant was phagocytosed and replicated to a greater extent and was more cytotoxic than Rough in macrophages. In contrast, multiple locus sequence type (MLST) analysis, ribotyping, and whole genome sequence analysis demonstrated the variants' genetic conservation; only a single consistent genetic difference between the two was identified for further study. These distinct differences shown by two variants of a Bp strain will be leveraged to better understand the mechanism of Bp phenotypic variability and to possibly identify in vitro markers of infection.

In vitro anti-tubulin effects of mebendazole and fenbendazole on canine glioma cells.

Benzimidazole anthelmintics have reported anti-neoplastic effects both in vitro and in vivo. The purpose of this study was to evaluate the in vitro chemosensitivity of three canine glioma cell lines to mebendazole and fenbendazole. The mean inhibitory concentration (IC50 ) (±SD) obtained from performing the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay after treating J3T, G06-A, and SDT-3G cells for 72 h with mebendazole were 0.030 ± 0.003, 0.080 ± 0.015 and 0.030 ± 0.006 µM respectively, while those for fenbendazole were 0.550 ± 0.015, 1.530 ± 0.159 and 0.690 ± 0.095 µM; treatment of primary canine fibroblasts for 72 h at IC50 showed no significant effect. Immunofluorescence studies showed disruption of tubulin after treatment. Mebendazole and fenbendazole are cytotoxic in canine glioma cell lines in vitro and may be good candidates for treatment of canine gliomas. Further in vivo studies are required.

Comparison of the proliferation and excretion of Bartonella quintana between body and head lice following oral challenge.

Human body and head lice are highly related haematophagous ectoparasites but only the body louse has been shown to transmit Bartonella quintana, the causative agent of trench fever. The mechanisms by which body lice became a vector for B. quintana, however, are poorly understood. Following oral challenge, green fluorescent protein-expressing B. quintana proliferated over 9 days postchallenge with the number of bacteria being significantly higher in whole body vs. head lice. The numbers of B. quintana detected in faeces from infected lice, however, were approximately the same in both lice. Nevertheless, the viability of B. quintana was significantly higher in body louse faeces. Comparison of immune responses in alimentary tract tissues revealed that basal transcription levels of peptidoglycan recognition protein and defensins were lower in body lice and the transcription of defensin 1 was up-regulated by oral challenge with wild-type B. quintana in head but not in body lice. In addition, the level of cytotoxic reactive oxygen species generated by epithelial cells was significantly lower in body lice. Although speculative at this time, the reduced immune response is consistent with the higher vector competence seen in body vs. head lice in terms of B. quintana infection.

Isolation of Bartonella henselae, Bartonella koehlerae subsp. koehlerae, Bartonella koehlerae subsp. bothieri and a new subspecies of B. koehlerae from free-ranging lions (Panthera leo) from South Africa, cheetahs (Acinonyx jubatus) from Namibia and captive cheetahs from California.

Bartonellae are blood- and vector-borne Gram-negative bacteria, recognized as emerging pathogens. Whole-blood samples were collected from 58 free-ranging lions (Panthera leo) in South Africa and 17 cheetahs (Acinonyx jubatus) from Namibia. Blood samples were also collected from 11 cheetahs (more than once for some of them) at the San Diego Wildlife Safari Park. Bacteria were isolated from the blood of three (5%) lions, one (6%) Namibian cheetah and eight (73%) cheetahs from California. The lion Bartonella isolates were identified as B. henselae (two isolates) and B. koehlerae subsp. koehlerae. The Namibian cheetah strain was close but distinct from isolates from North American wild felids and clustered between B. henselae and B. koehlerae. It should be considered as a new subspecies of B. koehlerae. All the Californian semi-captive cheetah isolates were different from B. henselae or B. koehlerae subsp. koehlerae and from the Namibian cheetah isolate. They were also distinct from the strains isolated from Californian mountain lions (Felis concolor) and clustered with strains of B. koehlerae subsp. bothieri isolated from free-ranging bobcats (Lynx rufus) in California. Therefore, it is likely that these captive cheetahs became infected by an indigenous strain for which bobcats are the natural reservoir.

Explanation of the size dependent in-plane optical resonance of triangular silver nanoprisms.

Triangular silver nanoprisms with thicknesses of 3-5 nm and adjustable edge lengths - which can lead to nanoparticles with aspect ratios up to 1 : 50 - are quasi-two-dimensional nanoparticles. Due to high ensemble homogeneities, which are achieved by the application of a microfluid segment based preparation method, the optical properties of the silver nanoprisms can be studied directly in colloidal solution. Investigations of the shift of the longitudinal main absorption peak with varying edge length lead to a semi-empiric model in which inelastic one-photon-one-electron processes are used to explain the found absorption behavior instead of the conventional interpretation of a collective oscillation of the conduction band electrons. Independently of the inserted seed particle volumes or amounts of silver ions, all measurement series follow a linear interrelation between the spectral position of the longitudinal absorption peak and the determined edge length of the nanoprisms, which leads to the derivation of a length constant b0, which in turn can be described within the framework of the model - next to a geometry factor - exclusively by natural constants. The proposed model describes the behavior of quasi-two-dimensional noble metal nanoparticles by a dualism between the assumption of "metallic molecules" and materials with "blurred bandgaps".

[Normal and Adventitious Breath Sounds]. / Atemgeräusche und Atem-Nebengeräusche.

Auscultation of the lung is an inexpensive, noninvasive and easy-to-perform tool. It is an important part of the physical examination and is help ful to distinguish physiological respiratory sounds from pathophysiological events. Computerized lung sound analysis is a powerful tool for optimizing and quantifying electronic auscultation based on the specific lung sound spectral characteristics. The automatic analysis of respiratory sounds assumes that physiological and pathological sounds are reliably analyzed based on special algorithms. The development of automated long-term lungsound monitors enables objective assessment of different respiratory symptoms.

Cytologic Criteria for Mast Cell Tumor Grading in Dogs With Evaluation of Clinical Outcome.

A 2-tiered histologic grading scheme for canine cutaneous mast cell tumors (MCTs) is based on morphologic characteristics of neoplastic cells, including karyomegaly, multinucleation, nuclear pleomorphism, and mitotic figures. Aspirates from MCTs may provide the same information more quickly, inexpensively, and less invasively. This study used these criteria to develop a cytologic grading scheme for canine MCTs to predict outcome. Three anatomic pathologists graded histologic samples from 152 canine MCTs. Three clinical pathologists evaluated aspirates from these masses using similar criteria. A cytologic grading scheme was created based on correlation with histologic grade and evaluated with a kappa statistic. Survival was evaluated with Kaplan-Meier survival curves. Cox proportional hazards regression was used to estimate hazard ratios for tumor grades and individual grading components. Simple logistic regression tested for relationships between risk factors and mortality. The cytologic grading scheme that best correlated with histology (kappa = 0.725 ± 0.085) classified a tumor as high grade if it was poorly granulated or had at least 2 of 4 findings: mitotic figures, binucleated or multinucleated cells, nuclear pleomorphism, or >50% anisokaryosis. The cytologic grading scheme had 88% sensitivity and 94% specificity relative to histologic grading. Dogs with histologic and cytologic high grade MCTs were 39 times and 25 times more likely to die within the 2-year follow-up period, respectively, than dogs with low grade MCTs. High tumor grade was associated with increased probability of additional tumors or tumor regrowth. This study concluded that cytologic grade is a useful predictor for treatment planning and prognostication.

Neprilysin inhibition with sacubitril/valsartan in the treatment of heart failure: mortality bang for your buck.

WHAT IS KNOWN AND OBJECTIVE: Heart failure remains a leading cause of morbidity and mortality worldwide. Advanced therapies have prolonged survival in patients with advanced heart failure, but pharmacotherapeutic optimization remains the mainstay of treatment. It has been over 10 years since the last mortality-reducing medication has been approved by the Food and Drug Administration. This article reviews the background, current knowledge and data supporting the use of sacubitril/valsartan (Entresto(®) ), the newly FDA-approved medication that dually inhibits angiotensin and neprilysin, in the treatment of heart failure. METHODS: A literature search was performed (January 1980 to August 2015) using PubMed and the search terms were as follows: neprilysin inhibitor, heart failure, endopeptidase, natriuretic peptides, angiotensin, omapatrilat, LCZ696, valsartan and sacubitril. Peer-reviewed, published clinical trials, review articles, relevant treatment guidelines and prescribing information documents were identified and reviewed for relevance. Additionally, reference citations from publications identified were reviewed. RESULTS AND DISCUSSION: The inhibition of endopeptidases has been an area of extensive study for the treatment of heart failure. Previously published literature with the endopeptidase inhibitor omapatrilat failed to demonstrate a sufficient balance between clinical efficacy and safety to justify its approval. Omapatrilat blocked three pathways that break down bradykinin, leading to high rates of angioedema. Sacubitril, on the other hand, is metabolized to a form that is highly selective for neprilysin without possessing activity for the other two peptidases, ACE and APP. The combination of sacubitril with valsartan in a single formulation offers the benefit of concurrent blockade of the renin angiotensin aldosterone system and the inhibition of neprilysin while minimizing angioedema risk. When compared to ACE inhibitor therapy in systolic heart failure patients, sacubitril/valsartan demonstrated reductions in all-cause mortality and hospitalization due to heart failure while maintaining a similar safety profile. WHAT IS NEW AND CONCLUSION: A formulation that contains both sacubitril and valsartan was manufactured and approved by the FDA in July 2015 for the reduction of mortality and hospitalization in systolic heart failure patients. The new medication offers a potentially superior alternative to ACE inhibitor therapy in the management of systolic heart failure. The effects of treatment with sacubitril/valsartan in the setting of diastolic heart failure are currently under investigation in clinical trials.

Evaluation of Study and Patient Characteristics of Clinical Studies in Primary Progressive Multiple Sclerosis: A Systematic Review.

BACKGROUND: So far, clinical studies in primary progressive MS (PPMS) have failed to meet their primary efficacy endpoints. To some extent this might be attributable to the choice of assessments or to the selection of the study population. OBJECTIVE: The aim of this study was to identify outcome influencing factors by analyzing the design and methods of previous randomized studies in PPMS patients without restriction to intervention or comparator. METHODS: A systematic literature search was conducted in MEDLINE, EMBASE, BIOSIS and the COCHRANE Central Register of Controlled Trials (inception to February 2015). Keywords included PPMS, primary progressive multiple sclerosis and chronic progressive multiple sclerosis. Randomized, controlled trials of at least one year's duration were selected if they included only patients with PPMS or if they reported sufficient PPMS subgroup data. No restrictions with respect to intervention or comparator were applied. Study quality was assessed by a biometrics expert. Relevant baseline characteristics and outcomes were extracted and compared. RESULTS: Of 52 PPMS studies identified, four were selected. Inclusion criteria were notably different among studies with respect to both the definition of PPMS and the requirements for the presence of disability progression at enrolment. Differences between the study populations included the baseline lesion load, pretreatment status and disease duration. The rate of disease progression may also be an important factor, as all but one of the studies included a large proportion of patients with a low progression rate. In addition, the endpoints specified could not detect progression adequately. CONCLUSION: Optimal PPMS study methods involve appropriate patient selection, especially regarding the PPMS phenotype and progression rate. Functional composite endpoints might be more sensitive than single endpoints in capturing progression.

A Novel Inherited Cerebellar Abiotrophy in a Cohort of Related Goats.

Cerebellar abiotrophies, also known as cerebellar ataxias, are characterized by premature post-natal degeneration of cerebellar neurons. This report describes the clinical, magnetic resonance imaging (MRI), gross, histopathological and immunohistochemical features of a novel inherited cerebellar abiotrophy in a cohort of three closely related mixed-breed goats (Capra aegagrus hircus) in the southeastern USA. The animals all presented with early juvenile-onset ataxia, hypermetria, wide-based stance, head tremors and nystagmus. On MRI and at gross examination, there was moderate thinning of the cerebellar vermis and sharpening of the folia. Histologically, the vermis, paravermis and flocculonodular lobe had moderate to severe segmental loss of Purkinje cells with sparing of the hemispheres and secondary loss of granule cells and astrogliosis. Heritable cerebellar ataxias have been reported in many domestic animal species, but not, to the authors' knowledge, as a heritable condition in goats.

[Tryptophan immunoadsorption for multiple sclerosis and neuromyelitis optica: therapy option for acute relapses during pregnancy and breastfeeding]. / Tryptophan-Immunadsorption bei Multipler Sklerose und Neuromyelitis optica : Therapieoption bei akuten Schüben in der Schwangerschaft und Stillphase.

BACKGROUND: Approximately 25 % of women with multiple sclerosis (MS) suffer clinically relevant relapses during pregnancy. Almost all disease-modifying drugs are contraindicated in pregnancy. High-dose glucocorticoids have some serious risks, especially within the first trimester. Tryptophan immunoadsorption (IA) provides a safe option to treat MS relapses during pregnancy. OBJECTIVES: In this case series we describe for the first time the use of tryptophan IA for MS and neuromyelitis optica (NMO) relapses during pregnancy and breastfeeding. PATIENTS AND METHODS: In this study a total of 9 patients were retrospectively analyzed of which 7 patients received IA treatment during pregnancy, 2 during breastfeeding and 4-6 tryptophan IA treatments were performed per patient with the single use tryptophan adsorber. Primary outcome was symptom improvement of the relapse. RESULTS: In this study four patients with MS and one with NMO relapse during pregnancy were treated with IA without preceding glucocorticoid pulse therapy. The MS patients showed improvement in the expanded disability status scale (EDSS) by at least one point, the NMO patient showed significant improvement in visual acuity and two pregnant patients with steroid-refractory relapses showed clinically relevant improvement after IA. Of the patients two suffered from steroid-refractory relapses during breastfeeding and relapse symptoms improved in both cases after treatment with IA. All treatments were well tolerated and no serious adverse events occurred. CONCLUSION: Tryptophan IA was found to be safe, well-tolerated and effective in the treatment of MS and NMO relapses during pregnancy and breastfeeding, sometimes without preceding glucocorticoid pulse therapy. A binding recommendation is limited without prospective clinical studies.