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Todd Lewis and co-authors discuss development and use of the People's Voice Survey for health system assessment.

The gastrointestinal and respiratory systems are closely linked in different ways, including from the embryological, anatomical, cellular, and physiological angles. The highest number (and various types) of microorganisms live in the large intestine/colon, and constitute the normal microbiota in healthy people. Adverse alterations of the microbiota or dysbiosis can lead to chronic inflammation. If this detrimental condition persists, a sequence of pathological events can occur, such as inflammatory bowel disease, dysplasia or premalignant changes, and finally, cancer. One of the most commonly identified bacteria in both inflammatory bowel disease and colon cancer is Escherichia coli. On the other hand, patients with inflammatory bowel disease are at risk of several other diseases—both intestinal (such as malnutrition and intestinal obstruction, besides cancer) and extraintestinal (such as arthritis, bronchiectasis, and cancer risk). Cancers of the lung and colon are the two most common malignancies occurring worldwide (except for female breast cancer). Like the bacterial role in colon cancer, many studies have shown a link between chronic Chlamydia pneumoniae infection and lung cancer. However, in colon cancer, genotoxic colibactin-producing E. coli belonging to the B2 phylogroup may promote tumorigenesis. Furthermore, E. coli is believed to play an important role in the dissemination of cancer cells from the primary colonic site. Currently, seven enteric pathogenic E. coli subtypes have been described. Conversely, three Chlamydiae can cause infections in humans (C. trachomatis may increase the risk of cervical and ovarian cancers). Nonetheless, striking genomic plasticity and genetic modifications allow E. coli to constantly adjust to the surrounding environment. Consequently, E. coli becomes resistant to antibiotics and difficult to manage. To solve this problem, scientists are thinking of utilizing suitable lytic bacteriophages (viruses that infect and kill bacteria). Several bacteriophages of E. coli and Chlamydia species are being evaluated for this purpose.

Fire is an integral component of ecosystems globally and a tool that humans have harnessed for millennia. Altered fire regimes are a fundamental cause and consequence of global change, impacting people and the biophysical systems on which they depend. As part of the newly emerging Anthropocene, marked by human-caused climate change and radical changes to ecosystems, fire danger is increasing, and fires are having increasingly devastating impacts on human health, infrastructure, and ecosystem services. Increasing fire danger is a vexing problem that requires deep transdisciplinary, trans-sector, and inclusive partnerships to address. Here, we outline barriers and opportunities in the next generation of fire science and provide guidance for investment in future research. We synthesize insights needed to better address the long-standing challenges of innovation across disciplines to (i) promote coordinated research efforts; (ii) embrace different ways of knowing and knowledge generation; (iii) promote exploration of fundamental science; (iv) capitalize on the "firehose" of data for societal benefit; and (v) integrate human and natural systems into models across multiple scales. Fire science is thus at a critical transitional moment. We need to shift from observation and modeled representations of varying components of climate, people, vegetation, and fire to more integrative and predictive approaches that support pathways toward mitigating and adapting to our increasingly flammable world, including the utilization of fire for human safety and benefit. Only through overcoming institutional silos and accessing knowledge across diverse communities can we effectively undertake research that improves outcomes in our more fiery future.

Summary: High-quality care is essential for improving health outcomes, although many health systems struggle to maintain good quality. We use data from the People's Voice Survey—a nationally representative survey conducted in 14 high-income, middle-income, and low-income countries—to describe user-reported quality of most recent health care in the past 12 months. We described ratings for 14 measures of care competence, system competence, and user experience and assessed the relationship between visit quality factors and user recommendation of the facility. We disaggregated the data by high-need and underserved groups. The proportion of respondents rating their most recent visit as high quality ranged from 25% in Laos to 74% in the USA. The mean facility recommendation score was 7·7 out of 10. Individuals with high needs or who are underserved reported lower-quality services on average across countries. Countries with high health expenditure per capita tended to have better care ratings than countries with low health expenditure. Visit quality factors explained a high proportion of variation in facility recommendations relative to facility or demographic factors. These results show that user-reported quality is low but increases with high national health expenditure. Elevating care quality will require monitoring and improvements on multiple dimensions of care quality, especially in public systems.

Summary: Population confidence is essential to a well functioning health system. Using data from the People's Voice Survey—a novel population survey conducted in 15 low-income, middle-income, and high-income countries—we report health system confidence among the general population and analyse its associated factors. Across the 15 countries, fewer than half of respondents were health secure and reported being somewhat or very confident that they could get and afford good-quality care if very sick. Only a quarter of respondents endorsed their current health system, deeming it to work well with no need for major reform. The lowest support was in Peru, the UK, and Greece—countries experiencing substantial health system challenges. Wealthy, more educated, young, and female respondents were less likely to endorse the health system in many countries, portending future challenges for maintaining social solidarity for publicly financed health systems. In pooled analyses, the perceived quality of the public health system and government responsiveness to public input were strongly associated with all confidence measures. These results provide a post-COVID-19 pandemic baseline of public confidence in the health system. The survey should be repeated regularly to inform policy and improve health system accountability.

Infection with the SARS-CoV-2 virus (COVID-19 disease) can cause a wide range of clinical situations – from an asymptomatic state to fatal outcomes. In cases of serious clinical manifestations, the underlying mechanisms involve a number of immune cells and stromal cells as well as their products such as pro-inflammatory interleukin-6 and tumour necrosis factor-alpha that ultimately cause the cytokine storm. The situation of overproduction of pro-inflammatory cytokines is somewhat similar to, though in a mild form, health conditions in obesity and related metabolic disorders like type-2 diabetes, which are also considered important risk factors for severe illness in COVID-19. Interestingly, neutrophils perhaps play a significant role in this pathogenesis. On the other hand, it is thought that COVID-19-related critical illness is associated with pathological hyperactivity of the complement system and coagulopathy. Although the precise molecular interactions between the complement and coagulation systems are not clear, we observe an intimate cross-talk between these two systems in critically ill COVID-19 patients. It is believed that both of these biological systems are connected with the cytokine storm in severe COVID-19 disease and actively participate in this vicious cycle. In order to hinder the pathological progression of COVID-19, a number of anticoagulation agents and complement inhibitors have been used with varying success. Among these drugs, low molecular weight heparin enoxaparin, factor Xa inhibitor apixaban, and complement C5 inhibitor eculizumab have been commonly used in patients with COVID-19. Our overall experience might help us in the future to tackle any such conditions.

Objective: With Huntington disease (HD), a fatal neurodegenerative disease where the prevalence of suicidal thoughts and behavior (STB) remains elevated as compared to other neurological disorders, it is unknown whether STB and health-related quality of life (HRQoL) affect plans for the end of life or more broadly, advance care planning (ACP). Conversely, it is unknown whether ACP would provoke future changes to STB and HRQoL. Therefore, we sought to evaluate whether STB and HRQoL patient-reported outcomes (PROs) contribute to ACP and whether ACP relates to changes in STB and HRQoL at 24 months. Methods: HD-validated clinician- and patient-assessments (i.e., HRQoL PROs) were obtained at baseline enrollment, 12 and 24 months through our multi-center study (HDQLIFE?) throughout the United States among people with premanifest, early-stage, and late-stage manifest HD. We used linear mixed-effects models to determine the relationships between STB and HRQoL at baseline and HDQLIFE End of Life Planning at follow-up. Separate linear mixed-effects models were used to assess the relationship between HDQLIFE End of Life Planning at baseline, and HRQoL and STB at 12 and 24 months. False discovery rate adjustments were used to account for multiple comparisons. Results: At baseline enrollment, STB and HRQoL were not related to HDQLIFE End of Life Planning at 12 or 24 months. Similarly, at baseline, HDQLIFE End of Life Planning demonstrated no association with STB or HRQoL at 12 or 24 months. Interpretation: STB and HRQoL PROs do not significantly affect patient engagement with ACP. Most importantly, engaging in ACP does not cause untoward effects on HRQoL or STB for this rare neurodegenerative disease where the lifetime prevalence of STB approaches 30%.

Todd Lewis and co-authors discuss development and use of the People's Voice Survey for health system assessment.

BackgroundProgressive supranuclear palsy (PSP) -Richardson's Syndrome and Corticobasal Syndrome (CBS) are the two classic clinical syndromes associated with underlying four repeat (4R) tau pathology. The PSP Rating Scale is a commonly used assessment in PSP clinical trials; there is an increasing interest in designing combined 4R tauopathy clinical trials involving both CBS and PSP.ObjectivesTo determine contributions of each domain of the PSP Rating Scale to overall severity and characterize the probable sequence of clinical progression of PSP as compared to CBS.MethodsMulticenter clinical trial and natural history study data were analyzed from 545 patients with PSP and 49 with CBS. Proportional odds models were applied to model normalized cross-sectional PSP Rating Scale, estimating the probability that a patient would experience impairment in each domain using the PSP Rating Scale total score as the index of overall disease severity.ResultsThe earliest symptom domain to demonstrate impairment in PSP patients was most likely to be Ocular Motor, followed jointly by Gait/Midline and Daily Activities, then Limb Motor and Mentation, and finally Bulbar. For CBS, Limb Motor manifested first and ocular showed less probability of impairment throughout the disease spectrum. An online tool to visualize predicted disease progression was developed to predict relative disability on each subscale per overall disease severity.ConclusionThe PSP Rating Scale captures disease severity in both PSP and CBS. Modelling how domains change in relation to one other at varying disease severities may facilitate detection of therapeutic effects in future clinical trials.

BackgroundAlterations in speech have long been identified as indicators of various neurologic conditions including traumatic brain injury, neurodegenerative diseases, and stroke. The extent to which speech errors occur in milder brain injuries, such as sports-related concussions, is unknown. The present study examined speech error rates in student athletes after a sports-related concussion compared to pre-injury speech performance in order to determine the presence and relevant characteristics of changes in speech production in this less easily detected neurologic condition.MethodsA within-subjects pre/post-injury design was used. A total of 359 Division I student athletes participated in pre-season baseline speech testing. Of these, 27 athletes (18–22 years) who sustained a concussion also participated in speech testing in the days immediately following diagnosis of concussion. Picture description tasks were utilized to prompt connected speech samples. These samples were recorded and then transcribed for identification of errors and disfluencies. These were coded by two trained raters using a 6-category system that included 14 types of error metrics.ResultsRepeated measures analysis of variance was used to compare the difference in error rates at baseline and post-concussion. Results revealed significant increases in the speech error categories of pauses and time fillers (interjections/fillers). Additionally, regression analysis showed that a different pattern of errors and disfluencies occur after a sports-related concussion (primarily time fillers) compared to pre-injury (primarily pauses).ConclusionResults demonstrate that speech error rates increase following even mild head injuries, in particular, sports-related concussion. Furthermore, the speech error patterns driving this increase in speech errors, rate of pauses and interjections, are distinct features of this neurological injury, which is in contrast with more severe injuries that are marked by articulation errors and an overall reduction in verbal output. Future studies should consider speech as a diagnostic tool for concussion.

ObjectiveTo determine the ability of CSF biomarkers to predict disease progression in progressive supranuclear palsy (PSP).MethodsWe compared the ability of baseline CSF β-amyloid1-42, tau, phosphorylated tau 181 (p-tau), and neurofilament light chain (NfL) concentrations, measured by INNO-BIA AlzBio3 or ELISA, to predict 52-week changes in clinical (PSP Rating Scale [PSPRS] and Schwab and England Activities of Daily Living [SEADL]), neuropsychological, and regional brain volumes on MRI using linear mixed effects models controlled for age, sex, and baseline disease severity, and Fisher F density curves to compare effect sizes in 50 patients with PSP. Similar analyses were done using plasma NfL measured by single molecule arrays in 141 patients.ResultsHigher CSF NfL concentration predicted more rapid decline (biomarker × time interaction) over 52 weeks in PSPRS (p = 0.004, false discovery rate-corrected) and SEADL (p = 0.008), whereas lower baseline CSF p-tau predicted faster decline on PSPRS (p = 0.004). Higher CSF tau concentrations predicted faster decline by SEADL (p = 0.004). The CSF NfL/p-tau ratio was superior for predicting change in PSPRS, compared to p-tau (p = 0.003) or NfL (p = 0.001) alone. Higher NfL concentrations in CSF or blood were associated with greater superior cerebellar peduncle atrophy (fixed effect, p ≤ 0.029 and 0.008, respectively).ConclusionsBoth CSF p-tau and NfL correlate with disease severity and rate of disease progression in PSP. The inverse correlation of p-tau with disease severity suggests a potentially different mechanism of tau pathology in PSP as compared to Alzheimer disease.

Abstract Background Dried blood spots (DBS) are a relatively inexpensive source of nucleic acids and are easy to collect, transport, and store in large-scale field surveys, especially in resource-limited settings. However, their performance in whole-genome sequencing (WGS) relative to that of venous blood DNA has not been analyzed for various downstream applications. Methods This study compares the WGS performance of DBS paired with venous blood samples collected from 12 subjects. Results Results of standard quality checks of coverage, base quality, and mapping quality were found to be near identical between DBS and venous blood. Concordance for single-nucleotide variants, insertions and deletions, and copy number variants was high between these two sample types. Additionally, downstream analyses typical of population-based studies were performed, such as mitochondrial heteroplasmy detection, haplotype analysis, mitochondrial copy number changes, and determination of telomere lengths. The absolute mitochondrial copy number values were higher for DBS than for venous blood, though the trend in sample-to-sample variation was similar between DBS and blood. Telomere length estimates in most DBS samples were on par with those from venous blood. Conclusion DBS samples can serve as a robust and feasible alternative to venous blood for studies requiring WGS analysis.

ObjectiveTo examine the utility and reliability of volumetric MRI in measuring disease progression in the 4 repeat tauopathies, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), to support clinical development of new tau-directed therapeutic agents.MethodsSix- and 12-month changes in regional MRI volumes and PSP Rating Scale scores were examined in 55 patients with PSP and 33 patients with CBS (78% amyloid PET negative) compared to 30 normal controls from a multicenter natural history study. Longitudinal voxel-based morphometric analyses identified patterns of volume loss, and region-of-interest analyses examined rates of volume loss in brainstem (midbrain, pons, superior cerebellar peduncle), cortical, and subcortical regions based on previously validated atlases. Results were compared to those in a replication cohort of 226 patients with PSP with MRI data from the AL-108-231 clinical trial.ResultsPatients with CBS exhibited greater baseline atrophy and greater longitudinal atrophy rates in cortical and basal ganglia regions than patients with PSP; however, midbrain and pontine atrophy rates were similar. Voxel-wise analyses showed distinct patterns of regional longitudinal atrophy in each group as compared to normal controls. The midbrain/pons volumetric ratio differed between diagnoses but remained stable over time. In both patient groups, brainstem atrophy rates were correlated with disease progression measured using the PSP Rating Scale.ConclusionsVolume loss is quantifiable over a period of 6 months in CBS and PSP. Future clinical trials may be able to combine CBS and PSP to measure therapeutic effects.

PurposeHuntington disease (HD) is a chronic, debilitating genetic disease that affects physical, emotional, cognitive, and social health. Existing patient-reported outcomes (PROs) of health-related quality of life (HRQOL) used in HD are neither comprehensive, nor do they adequately account for clinically meaningful changes in function. While new PROs examining HRQOL (i.e., Neuro-QoL-Quality of Life in Neurological Disorders and PROMIS-Patient-Reported Outcomes Measurement Information System) offer solutions to many of these shortcomings, they do not include HD-specific content, nor have they been validated in HD. HDQLIFE addresses this by validating 12 PROMIS/Neuro-QoL domains in individuals with HD and by using established PROMIS methodology to develop new, HD-specific content.MethodsNew item pools were developed using cognitive debriefing with individuals with HD, and expert, literacy, and translatability reviews. Existing item banks and new item pools were field tested in 536 individuals with prodromal, early-, or late-stage HD.ResultsModerate to strong relationships between Neuro-QoL/PROMIS measures and generic self-report measures of HRQOL, and moderate relationships between Neuro-QoL/PROMIS and clinician-rated measures of similar constructs supported the validity of Neuro-QoL/PROMIS in individuals with HD. Exploratory and confirmatory factor analysis, item response theory, and differential item functioning analyses were utilized to develop new item banks for Chorea, Speech Difficulties, Swallowing Difficulties, and Concern with Death and Dying, with corresponding six-item short forms. A four-item short form was developed for Meaning and Purpose.ConclusionsHDQLIFE encompasses both validated Neuro-QoL/PROMIS measures, as well as five new scales in order to provide a comprehensive assessment of HRQOL in HD.

China has pledged reduction of carbon dioxide (CO2) emissions per unit of gross domestic product (GDP) by 60 %–65 % relative to 2005 levels, and to peak carbon emissions overall by 2030. However, the lack of observational data and disagreement among the many available inventories makes it difficult for China to track progress toward these goals and evaluate the efficacy of control measures. To demonstrate the value of atmospheric observations for constraining CO2 inventories we track the ability of CO2 concentrations predicted from three different CO2 inventories to match a unique multi-year continuous record of atmospheric CO2. Our analysis time window includes the key commitment period for the Paris Agreement (2005) and the Beijing Olympics (2008). One inventory is China-specific and two are spatial subsets of global inventories. The inventories differ in spatial resolution, basis in national or subnational statistics, and reliance on global or China-specific emission factors. We use a unique set of historical atmospheric observations from 2005 to 2009 to evaluate the three CO2 emissions inventories within China's heavily industrialized and populated northern region accounting for ∼33 %–41 % of national emissions. Each anthropogenic inventory is combined with estimates of biogenic CO2 within a high-resolution atmospheric transport framework to model the time series of CO2 observations. To convert the model–observation mismatch from mixing ratio to mass emission rates we distribute it over a region encompassing 90 % of the total surface influence in seasonal (annual) averaged back-trajectory footprints (L_0.90 region). The L_0.90 region roughly corresponds to northern China. Except for the peak growing season, where assessment of anthropogenic emissions is entangled with the strong vegetation signal, we find the China-specific inventory based on subnational data and domestic field studies agrees significantly better with observations than the global inventories at all timescales. Averaged over the study time period, the unscaled China-specific inventory reports substantially larger annual emissions for northern China (30 %) and China as a whole (20 %) than the two unscaled global inventories. Our results, exploiting a robust time series of continuous observations, lend support to the rates and geographic distribution in the China-specific inventory Though even long-term observations at a single site reveal differences among inventories, exploring inventory discrepancy over all of China requires a denser observational network in future efforts to measure and verify CO2 emissions for China both regionally and nationally. We find that carbon intensity in the northern China region has decreased by 47 % from 2005 to 2009, from approximately 4 kg of CO2 per USD (note that all references to USD in this paper refer to USD adjusted for purchasing power parity, PPP) in 2005 to about 2 kg of CO2 per USD in 2009 (Fig. 9c). However, the corresponding 18 % increase in absolute emissions over the same time period affirms a critical point that carbon intensity targets in emerging economies can be at odds with making real climate progress. Our results provide an important quantification of model–observation mismatch, supporting the increased use and development of China-specific inventories in tracking China's progress as a whole towards reducing emissions. We emphasize that this work presents a methodology for extending the analysis to other inventories and is intended to be a comparison of a subset of anthropogenic CO2 emissions rates from inventories that were readily available at the time this research began. For this study's analysis time period, there was not enough spatially distinct observational data to conduct an optimization of the inventories. The primary intent of the comparisons presented here is not to judge specific inventories, but to demonstrate that even a single site with a long record of high-time-resolution observations can identify major differences among inventories that manifest as biases in the model–data comparison. This study provides a baseline analysis for evaluating emissions from a small but important region within China, as well a guide for determining optimal locations for future ground-based measurement sites.

Accurately quantifying the spatiotemporal distribution of the biological component of CO2 surface–atmosphere exchange is necessary to improve top-down constraints on China's anthropogenic CO2 emissions. We provide hourly fluxes of CO2 as net ecosystem exchange (NEE; µmol CO2 m−2 s−1) on a 0.25° × 0.25° grid by adapting the Vegetation, Photosynthesis, and Respiration Model (VPRM) to the eastern half of China for the time period from 2005 to 2009; the minimal empirical parameterization of the VPRM-CHINA makes it well suited for inverse modeling approaches. This study diverges from previous VPRM applications in that it is applied at a large scale to China's ecosystems for the first time, incorporating a novel processing framework not previously applied to existing VPRM versions. In addition, the VPRM-CHINA model prescribes methods for addressing dual-cropping regions that have two separate growing-season modes applied to the same model grid cell. We evaluate the VPRM-CHINA performance during the growing season and compare to other biospheric models. We calibrate the VPRM-CHINA with ChinaFlux and FluxNet data and scale up regionally using Weather Research and Forecasting (WRF) Model v3.6.1 meteorology and MODIS surface reflectances. When combined with an anthropogenic emissions model in a Lagrangian particle transport framework, we compare the ability of VPRM-CHINA relative to an ensemble mean of global hourly flux models (NASA CMS – Carbon Monitoring System) to reproduce observations made at a site in northern China. The measurements are heavily influenced by the northern China administrative region. Modeled hourly time series using vegetation fluxes prescribed by VPRM-CHINA exhibit low bias relative to measurements during the May–September growing season. Compared to NASA CMS subset over the study region, VPRM-CHINA agrees significantly better with measurements. NASA CMS consistently underestimates regional uptake in the growing season. We find that during the peak growing season, when the heavily cropped North China Plain significantly influences measurements, VPRM-CHINA models a CO2 uptake signal comparable in magnitude to the modeled anthropogenic signal. In addition to demonstrating efficacy as a low-bias prior for top-down CO2 inventory optimization studies using ground-based measurements, high spatiotemporal resolution models such as the VPRM are critical for interpreting retrievals from global CO2 remote-sensing platforms such as OCO-2 and OCO-3 (planned). Depending on the satellite time of day and season of crossover, efforts to interpret the relative contribution of the vegetation and anthropogenic components to the measured signal are critical in key emitting regions such as northern China – where the magnitude of the vegetation CO2 signal is shown to be equivalent to the anthropogenic signal.

Abstract Background Priority setting in a climate of diverse needs and limited resources is one of the most significant challenges faced by health care policymakers. This paper develops and applies a comprehensive multi-criteria algorithm to help determine the relative importance of health conditions that affect a defined population. Methods Our algorithm is implemented in the context of the Waikato District Health Board (WDHB) in New Zealand, which serves approximately 10% of the New Zealand population. Strategic priorities of the WDHB are operationalized into five criteria along which the algorithm is structured—scale of disease, household financial impact of disease, health equity, cost-effectiveness, and multimorbidity burden. Using national-level data and published literature from New Zealand, the World Health Organization, and other high-income Commonwealth countries, 25 health conditions in Waikato are identified and mapped to these five criteria. These disease-criteria mappings are weighted with data from an ordered choice survey administered to the general public of the Waikato region. The resulting output of health conditions ranked in order of relative importance is validated against an explicit list of health concerns, provided by the survey respondents. Results Heart disease and cancerous disorders are assigned highest priority rankings according to both the algorithm and the survey data, suggesting that our model is aligned with the primary health concerns of the general public. All five criteria are weighted near-equal across survey respondents, though the average health equity preference score is 9.2% higher for Māori compared to non-Māori respondents. Older respondents (50 years and above) ranked issues of multimorbidity 4.2% higher than younger respondents. Conclusions Health preferences of the general population can be elicited using ordered-choice surveys and can be used to weight data for health conditions across multiple criteria, providing policymakers with a practical tool to inform which health conditions deserve the most attention. Our model connects public health strategic priorities, the health impacts and financial costs of particular health conditions, and the underlying preferences of the general public. We illustrate a practical approach to quantifying the foundational criteria that drive public preferences, for the purpose of relevant, legitimate, and evidence-based priority setting in health.

Mediastinal cysts account for 20% of all mediastinal masses. A 22-year-old pregnant female was admitted for delivery. She developed dyspnea on the 3rd day of delivery. Chest X-ray revealed a large right hydropneumothorax and tube thoracostomy was done. She was referred to us for further management. We decided to operate. At surgery, a ruptured cystic lesion was seen in the posterior mediastinum separate from all three lobes. It was communicating with the bronchus. The cyst was excised completely and bronchial communication was sutured. The lung expanded completely. Post operative period was uneventful. Histopathology revealed it to be a bronchogenic cyst.

Mediastinal cysts account for 20% of all mediastinal masses. A 22-year-old pregnant female was admitted for delivery. She developed dyspnea on the 3rd day of delivery. Chest X-ray revealed a large right hydropneumothorax and tube thoracostomy was done. She was referred to us for further management. We decided to operate. At surgery, a ruptured cystic lesion was seen in the posterior mediastinum separate from all three lobes. It was communicating with the bronchus. The cyst was excised completely and bronchial communication was sutured. The lung expanded completely. Post operative period was uneventful. Histopathology revealed it to be a bronchogenic cyst.

Background: Fluent speakers and people who stutter manifest alterations in autonomic and emotional responses as they view stuttered relative to fluent speech samples. These reactions are indicative of an aroused autonomic state and are hypothesized to be triggered by the abrupt breakdown in fluency exemplified in stuttered speech. Furthermore, these reactions are assumed to be the basis for the stereotypes held by different communicative partners towards people who stutter. Aims: To examine the autonomic and emotional reactions of graduate student clinicians in speech-language pathology as they viewed fluent and severe stuttered speech samples. Methods & Procedures: Twenty-one female graduate student clinicians in speech-language pathology participated in this study. Each participant viewed four 30-s video samples (two fluent and two stuttered speech samples) while their autonomic responses (skin conductance response (SCR) and heart rate (HR)) were concurrently captured. Furthermore, emotional responses to stuttered and fluent speech samples were captured using the self-assessment manikin (SAM) and a rating scale with nine bipolar adjectives reflecting one's feelings. Outcomes & Results: An increase in SCR and deceleration in HR was observed as graduate clinicians viewed stuttered speech samples versus fluent speech samples and the differences were statistically significant. In addition, results from the self-rating scales showed that participants had negative feelings (e.g., emotionally aroused, unpleasant, embarrassed, uncomfortable, etc.) while viewing stuttered speech. Conclusions & Implications: Findings suggest that graduate student clinicians in speech-language pathology demonstrated altered autonomic and emotional responses similar to those manifested by fluent and stuttered speakers as they viewed stuttered speech samples. Collectively, these findings support the contention that the inherent nature of stuttered speech triggers a visceral reaction in a listener, irrespective of their background and knowledge about the disorder. (Contains 2 tables.)

Background: Speech and language therapists treating children who stutter appear to be assigned a difficult task. Natural spontaneous remission accounts for approximately 60-80% of all children recovering from stuttering. Despite our best efforts, no protocol has ever shown its effectiveness separate from natural recovery rates (i.e. 60-80%). Although speech and language therapists have used a vast array of therapeutic protocols, the incidence and prevalence of childhood stuttering appears to have remained unchanged. Therefore, although in possession of multiple treatment tools, speech and language therapists might be ill-equipped to treat stuttering children effectively and efficiently to the point of recovery. Aim: To assess speech and language therapists' self-reported perceptions of their success in helping children "completely recover from stuttering" (i.e. no longer exhibiting any overt or covert stuttering symptoms or using therapeutic strategies to modify speech and no longer being viewed by themselves or anyone else as a "stutterer"). Methods & Procedures: A questionnaire was sent to 290 speech and language therapists providing stuttering therapy to children attending school in North Carolina, USA, in a system similar to what can be found in many other US states. It addressed therapeutic efficacy in the management of stuttering: the numbers of stuttering children treated and those perceived to be recovered, the therapeutic methods, the time spent in practice, therapy durations and schedules. Outcomes & Results: Usable questionnaires were returned by 101 respondents who reported treating a total of 2036 children who stutter. They reported using a full array of techniques known to reduce stuttering. The median reported recovery rate among respondents was 13.9%. Twenty-eight respondents reported no recoveries whatsoever, and 81 reported five recoveries or fewer. The median time spent on a caseload was 3 years. In addition, longer practising therapists repory higher recover rates than those with less time practising. Conclusions: Remission from stuttering in children being treated in the schools of North Carolina appears to be the exception rather than the rule. The reported recovery rates suggest that not much is being done therapeutically to help children recover from stuttering. The chance of recovery decreases with age, and speech therapy for children who stutter appears to do little to improve their odds of recovery. Speech and language therapists treating these children either do not possess the tools or the tools do not yet exist to change "nature's" recovery agendum and put children who stutter on the path towards natural sounding, fluent and spontaneous in all situations. As such, the provision of therapy, in North Carolina at least, does not yet allow for stuttering children to shed the label of "stutterer", in their own eyes and in the eyes of all others for the rest of their lives. In light of these data, the authors suggest re-examining the tools, policies and procedures used in the treatment of stuttering children.

Soil uptake of atmospheric hydrogen (H2) and the associated hydrogen isotope effect were studied using soil chambers in a Western Washington second-growth coniferous forest. Chamber studies were conducted during both winter and summer seasons to account for large natural variability in soil moisture content (4–50%) and temperature (6–22 °C). H2 deposition velocities were found to range from 0.01–0.06 cm s−1 with an average of 0.033 ± 0.008 cm s−1 (95% confidence interval). Consistent with prior studies, deposition velocities were correlated with soil moisture below 20% soil moisture content during the summer season. During winter, there was considerable variability observed in deposition velocity that was not closely related to soil moisture. The hydrogen kinetic isotope effect with H2 uptake was found to range from −24‰ to −109‰. Aggregate analysis of experimental data results in an average KIE of −57 ± 5‰ (95% CI). Some of the variability in KIE can be explained by larger isotope effects at lower (30%) soil moisture contents. The measured KIE was also found to be correlated with deposition velocity, with smaller isotope effects occurring at higher deposition velocities. If correct, these findings will have an impact on the interpretation of atmospheric measurements and modeling of δD of H2.

Objective : To evaluate the expression pattern of epidermal growth factor receptor (EGFR) in urinary bladder cancer and its association with human epidermal growth factor receptor 2 (HER2), epidermal growth factor (EGF), interleukin-6 (IL-6), and high risk human papilloma virus (HPV) types 16 and 18. Materials and Methods : Thirty cases of urothelial carcinoma were analyzed. EGFR, HER2, EGF, and IL-6 expressions in the tissue were evaluated by immunohistochemical staining. For HPV, DNA from tissue samples was extracted and detection of HPV was done by PCR technique. Furthermore, evaluation of different intracellular molecules associated with EGFR signaling pathways was performed by the western blot method using lysates from various cells and tissues. Results : In this study, the frequencies of immunopositivity for EGFR, HER2, EGF, and IL-6 were 23%, 60%, 47%, and 80%, respectively. No cases were positive for HPV-18, whereas HPV-16 was detected in 10% cases. Overall, expression of EGFR did not show any statistically significant association with the studied parameters. However, among male patients, a significant association was found only between EGFR and HER2. Conclusions : Overexpression of EGFR and/or HER2, two important members of the same family of growth factor receptors, was observed in a considerable proportion of cases. Precise knowledge in this subject would be helpful to formulate a rational treatment strategy in patients with urinary bladder cancer.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is characterized by dopamine depletion in the striatum. One consistent pathophysiological hallmark of PD is an increase in spontaneous oscillatory activity in the basal ganglia thalamocortical networks. We evaluated these effects using resting state functional connectivity MRI (fcMRI) in mild to moderate stage Parkinson’s patients on and off L-DOPA and age-matched controls using six different striatal seed regions. We observed an overall increase in the strength of cortico-striatal functional connectivity in PD patients off L-DOPA compared to controls. This enhanced connectivity was down-regulated by L-DOPA as shown by an overall decrease in connectivity strength, particularly within motor cortical regions. We also performed a frequency content analysis of the BOLD signal time course extracted from the six striatal seed regions. PD off L-DOPA exhibited increased power in the frequency band 0.02 – 0.05 Hz compared to controls and to PD on L-DOPA. The L-DOPA associated decrease in the power of this frequency range modulated the L-DOPA associated decrease in connectivity strength between striatal seeds and the thalamus. In addition, the L-DOPA associated decrease in power in this frequency band also correlated with the L-DOPA associated improvement in cognitive performance. Our results demonstrate that PD and L-DOPA modulate striatal resting state BOLD signal oscillations and corticostriatal network coherence.