Hearing-Related Quality of Life in 75 Patients With a Percutaneous Bone Conduction Device

Objective: To evaluate long-term hearing-related quality of life (HRQoL) and device use in bone conduction (BCD) users. Furthermore, to assess differences between indications and changes in HRQoL over time. Study design: Prospective questionnaire survey. Setting: Tertiary referral center. Patients: Seventy-five patients with a percutaneous BCD. Main outcome measures: Glasgow Benefit Inventory (GBI) at 3 and 12 months postoperatively, Glasgow Health Status Inventory (GHSI) preoperatively, and 6 and 36 months postoperatively, device use at 6, 12, and 36 months. Changes over time were assessed and outcomes were compared between indications. Results: After implantation, 97% of all patients reported a positive benefit on the GBI total. The GHSI total had improved with median 15 points (Interquartile range [IQR] 12). At 36 months, median device use was 15 hours/day (IQR 10) and one nonuser was reported. Patients with bilateral hearing loss (BHL) showed greater improvement on the GHSI total (median 18 vs 14, p &lt; 0.0001) and used their devices more frequently (median 16 vs 8 h/day, p &lt; 0.0001) than patients with unilateral HL (UHL). Postoperative GHSI and GBI scores were consistent over time, in the entire patient population and for every indication. Between 6 and 36 months, device use was stable over time, except for patients with single-sided deafness (SSD; median -6.4 h/day, p = 0.009). Conclusion: The BCD improves HRQoL in patients with BHL, in patients with unilateral conductive/mixed hearing loss and in patients with SSD. Patients with BHL experienced a greater improvement in hearing status compared to patients with UHL. Although use decreased over time in SSD patients, device use was high for every indication.</p

Translational evidence for two distinct patterns of neuroaxonal injury in sepsis: a longitudinal, prospective translational study

Background Brain homeostasis deteriorates in sepsis, giving rise to a mostly reversible sepsis-associated encephalopathy (SAE). Some survivors experience chronic cognitive dysfunction thought to be caused by permanent brain injury. In this study, we investigated neuroaxonal pathology in sepsis. Methods We conducted a longitudinal, prospective translational study involving (1) experimental sepsis in an animal model; (2) postmortem studies of brain from patients with sepsis; and (3) a prospective, longitudinal human sepsis cohort study at university laboratory and intensive care units (ICUs). Thirteen ICU patients with septic shock, five ICU patients who died as a result of sepsis, fourteen fluid-resuscitated Wistar rats with fecal peritonitis, eleven sham-operated rats, and three human and four rat control subjects were included. Immunohistologic and protein biomarker analysis were performed on rat brain tissue at baseline and 24, 48, and 72 h after sepsis induction and in sham-treated rats. Immunohistochemistry was performed on human brain tissue from sepsis nonsurvivors and in control patients without sepsis. The clinical diagnostics of SAE comprised longitudinal clinical data collection and magnetic resonance imaging (MRI) and electroencephalographic assessments. Statistical analyses were performed using SAS software (version 9.4; SAS Institute, Inc., Cary, NC, USA). Because of non-Gaussian distribution, the nonparametric Wilcoxon test general linear models and the Spearman correlation coefficient were used. Results In postmortem rat and human brain samples, neurofilament phosphoform, β-amyloid precursor protein, β-tubulin, and H&E stains distinguished scattered ischemic lesions from diffuse neuroaxonal injury in septic animals, which were absent in controls. These two patterns of neuroaxonal damage were consistently found in septic but not control human postmortem brains. In experimental sepsis, the time from sepsis onset correlated with tissue neurofilament levels (R = 0.53, p = 0.045) but not glial fibrillary acidic protein. Of 13 patients with sepsis who had clinical features of SAE, MRI detected diffuse axonal injury in 9 and ischemia in 3 patients. Conclusions Ischemic and diffuse neuroaxonal injury to the brain in experimental sepsis, human postmortem brains, and in vivo MRI suggest these two distinct lesion types to be relevant. Future studies should be focused on body fluid biomarkers to detect and monitor brain injury in sepsis. The relationship of neurofilament levels with time from sepsis onset may be of prognostic value

Small Molecule Enhancers of Endosome-to-Cytosol Import Augment Anti-tumor Immunity

Cross-presentation of antigens by dendritic cells (DCs) is critical for initiation of anti-tumor immune responses. Yet, key steps involved in trafficking of antigens taken up by DCs remain incompletely understood. Here, we screen 700 US Food and Drug Administration (FDA)-approved drugs and identify 37 enhancers of antigen import from endolysosomes into the cytosol. To reveal their mechanism of action, we generate proteomic organellar maps of control and drug-treated DCs (focusing on two compounds, prazosin and tamoxifen). By combining organellar mapping, quantitative proteomics, and microscopy, we conclude that import enhancers undergo lysosomal trapping leading to membrane permeation and antigen release. Enhancing antigen import facilitates cross-presentation of soluble and cell-associated antigens. Systemic administration of prazosin leads to reduced growth of MC38 tumors and to a synergistic effect with checkpoint immunotherapy in a melanoma model. Thus, inefficient antigen import into the cytosol limits antigen cross-presentation, restraining the potency of anti-tumor immune responses and efficacy of checkpoint blockers

Global Disease Outbreaks Associated with the 2015–2016 El Niño Event

Interannual climate variability patterns associated with the El Niño-Southern Oscillation phenomenon result in climate and environmental anomaly conditions in specific regions worldwide that directly favor outbreaks and/or amplification of variety of diseases of public health concern including chikungunya, hantavirus, Rift Valley fever, cholera, plague, and Zika. We analyzed patterns of some disease outbreaks during the strong 2015–2016 El Niño event in relation to climate anomalies derived from satellite measurements. Disease outbreaks in multiple El Niño-connected regions worldwide (including Southeast Asia, Tanzania, western US, and Brazil) followed shifts in rainfall, temperature, and vegetation in which both drought and flooding occurred in excess (14–81% precipitation departures from normal). These shifts favored ecological conditions appropriate for pathogens and their vectors to emerge and propagate clusters of diseases activity in these regions. Our analysis indicates that intensity of disease activity in some ENSO-teleconnected regions were approximately 2.5–28% higher during years with El Niño events than those without. Plague in Colorado and New Mexico as well as cholera in Tanzania were significantly associated with above normal rainfall (p \u3c 0.05); while dengue in Brazil and southeast Asia were significantly associated with above normal land surface temperature (p \u3c 0.05). Routine and ongoing global satellite monitoring of key climate variable anomalies calibrated to specific regions could identify regions at risk for emergence and propagation of disease vectors. Such information can provide sufficient lead-time for outbreak prevention and potentially reduce the burden and spread of ecologically coupled diseases

Factors that contribute to social media influence within an Internal Medicine Twitter learning community

Medical societies, faculty, and trainees use Twitter to learn from and educate other social media users. These social media communities bring together individuals with various levels of experience. It is not known if experienced individuals are also the most influential members. We hypothesize that participants with the greatest experience would be the most influential members of a Twitter community. We analyzed the 2013 Association of Program Directors in Internal Medicine Twitter community. We measured the number of tweets authored by each participant and the number of amplified tweets (re-tweets). We developed a multivariate linear regression model to identify any relationship to social media influence, measured by the PageRank. Faculty (from academic institutions) comprised 19% of the 132 participants in the learning community (p < 0.0001). Faculty authored 49% of all 867 tweets (p < 0.0001). Their tweets were the most likely to be amplified (52%, p < 0.01). Faculty had the greatest influence amongst all participants (mean 1.99, p < 0.0001). Being a faculty member had no predictive effect on influence (β = 0.068, p = 0.6). The only factors that predicted influence (higher PageRank) were the number of tweets authored (p < 0.0001) and number of tweets amplified (p < 0.0001) The status of “faculty member� did not confer a greater influence. Any participant who was able to author the greatest number of tweets or have more of his/her tweets amplified could wield a greater influence on the participants, regardless of his/her authority

Social media use, attitudes, behaviours and perceptions of online professionalism amongst dental students

Use of social media has increased amongst health professionals. This has benefits for patient care but also introduces risks for confidentiality and professional fitness to practise. This study aimed to examine dental student attitudes towards professional behaviour on social media. The secondary aim was to establish the extent and nature of social media use and exposure to potentially unprofessional behaviours. A cross-sectional study was carried out in one dental school. Data were collected using questionnaires to examine social media use, perceptions and attitudes towards social media and professional behaviours online. Students who responded (n=155) all used social media at least once per week; most used more than one platform. Students were aware of the relationship between social media use and professional practice. Posting drunken photographs and interacting with staff and patients online were widely considered as unprofessional. Security settings affected behaviour and most had seen inappropriate behaviours online. Students use social media extensively. Students are aware of the risks but there is a greater sense of safety in closed groups and many students are exposed to potentially inappropriate content online. This suggests that there are opportunities to reduce these risks through training to help students manage these risks

Detailed spectral and morphological analysis of the shell type SNR RCW 86

Aims: We aim for an understanding of the morphological and spectral properties of the supernova remnant RCW~86 and for insights into the production mechanism leading to the RCW~86 very high-energy gamma-ray emission. Methods: We analyzed High Energy Spectroscopic System data that had increased sensitivity compared to the observations presented in the RCW~86 H.E.S.S. discovery publication. Studies of the morphological correlation between the 0.5-1~keV X-ray band, the 2-5~keV X-ray band, radio, and gamma-ray emissions have been performed as well as broadband modeling of the spectral energy distribution with two different emission models. Results:We present the first conclusive evidence that the TeV gamma-ray emission region is shell-like based on our morphological studies. The comparison with 2-5~keV X-ray data reveals a correlation with the 0.4-50~TeV gamma-ray emission.The spectrum of RCW~86 is best described by a power law with an exponential cutoff at $E_{cut}=(3.5\pm 1.2_{stat})$ TeV and a spectral index of $\Gamma$~$1.6\pm 0.2$. A static leptonic one-zone model adequately describes the measured spectral energy distribution of RCW~86, with the resultant total kinetic energy of the electrons above 1 GeV being equivalent to $\sim$0.1\% of the initial kinetic energy of a Type I a supernova explosion. When using a hadronic model, a magnetic field of $B$~100$\mu$G is needed to represent the measured data. Although this is comparable to formerly published estimates, a standard E$^{-2}$ spectrum for the proton distribution cannot describe the gamma-ray data. Instead, a spectral index of $\Gamma_p$~1.7 would be required, which implies that ~$7\times 10^{49}/n_{cm^{-3}}$erg has been transferred into high-energy protons with the effective density $n_{cm^{-3}}=n/ 1$ cm^-3. This is about 10\% of the kinetic energy of a typical Type Ia supernova under the assumption of a density of 1~cm^-3.Comment: accepted for publication by A&

Characterizing the gamma-ray long-term variability of PKS 2155-304 with H.E.S.S. and Fermi-LAT

Studying the temporal variability of BL Lac objects at the highest energies provides unique insights into the extreme physical processes occurring in relativistic jets and in the vicinity of super-massive black holes. To this end, the long-term variability of the BL Lac object PKS 2155-304 is analyzed in the high (HE, 100 MeV 200 GeV) gamma-ray domain. Over the course of ~9 yr of H.E.S.S observations the VHE light curve in the quiescent state is consistent with a log-normal behavior. The VHE variability in this state is well described by flicker noise (power-spectral-density index {\ss}_VHE = 1.10 +0.10 -0.13) on time scales larger than one day. An analysis of 5.5 yr of HE Fermi LAT data gives consistent results ({\ss}_HE = 1.20 +0.21 -0.23, on time scales larger than 10 days) compatible with the VHE findings. The HE and VHE power spectral densities show a scale invariance across the probed time ranges. A direct linear correlation between the VHE and HE fluxes could neither be excluded nor firmly established. These long-term-variability properties are discussed and compared to the red noise behavior ({\ss} ~ 2) seen on shorter time scales during VHE-flaring states. The difference in power spectral noise behavior at VHE energies during quiescent and flaring states provides evidence that these states are influenced by different physical processes, while the compatibility of the HE and VHE long-term results is suggestive of a common physical link as it might be introduced by an underlying jet-disk connection.Comment: 11 pages, 16 figure

Structure–property relation and relevance of beam theories for microtubules: a coupled molecular and continuum mechanics study

Quasi-one-dimensional microtubules (MTs) in cells enjoy high axial rigidity but large transverse flexibility due to the inter-protofilament (PF) sliding. This study aims to explore the structure–property relation for MTs and examine the relevance of the beam theories to their unique features. A molecular structural mechanics (MSM) model was used to identify the origin of the inter-PF sliding and its role in bending and vibration of MTs. The beam models were then fitted to the MSM to reveal how they cope with the distinct mechanical responses induced by the inter-PF sliding. Clear evidence showed that the inter-PF sliding is due to the soft inter-PF bonds and leads to the length-dependent bending stiffness. The Euler beam theory is found to adequately describe MT deformation when the inter-PF sliding is largely prohibited. Nevertheless, neither shear deformation nor the nonlocal effect considered in the ‘more accurate’ beam theories can fully capture the effect of the inter-PF sliding. This reflects the distinct deformation mechanisms between an MT and its equivalent continuous body

Partition function zeros for the Ising model on complete graphs and on annealed scale-free networks

We analyze the partition function of the Ising model on graphs of two different types: complete graphs, wherein all nodes are mutually linked and annealed scale-free networks for which the degree distribution decays as $P(k)\sim k^{-\lambda}$. We are interested in zeros of the partition function in the cases of complex temperature or complex external field (Fisher and Lee-Yang zeros respectively). For the model on an annealed scale-free network, we find an integral representation for the partition function which, in the case $\lambda > 5$, reproduces the zeros for the Ising model on a complete graph. For $3<\lambda < 5$ we derive the $\lambda$-dependent angle at which the Fisher zeros impact onto the real temperature axis. This, in turn, gives access to the $\lambda$-dependent universal values of the critical exponents and critical amplitudes ratios. Our analysis of the Lee-Yang zeros reveals a difference in their behaviour for the Ising model on a complete graph and on an annealed scale-free network when $3<\lambda <5$. Whereas in the former case the zeros are purely imaginary, they have a non zero real part in latter case, so that the celebrated Lee-Yang circle theorem is violated.Comment: 36 pages, 31 figure