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Biodiversity is being lost at an unprecedented rate, and monitoring is crucial for understanding the causal drivers and assessing solutions. Most biodiversity monitoring data are collected by volunteers through citizen science projects, and often crucial information is lacking to account for the inevitable biases that observers introduce during data collection. We contend that citizen science projects intended to support biodiversity monitoring must gather information about the observation process as well as species occurrence. We illustrate this using eBird, a global citizen science project that collects information on bird occurrences as well as vital contextual information on the observation process while maintaining broad participation. Our fundamental argument is that regardless of what species are being monitored, when citizen science projects collect a small set of basic information about how participants make their observations, the scientific value of the data collected will be dramatically improved.

Citizen science data are valuable for addressing a wide range of ecological research questions, and there has been a rapid increase in the scope and volume of data available. However, data from large-scale citizen science projects typically present a number of challenges that can inhibit robust ecological inferences. These challenges include: species bias, spatial bias, and variation in effort.To demonstrate addressing key challenges in analysing citizen science data, we use the example of estimating species distributions with data from eBird, a large semi-structured citizen science project. We estimate two widely applied metrics of species distributions: encounter rate and occupancy probability. For each metric, we assess the impact of data processing steps that either degrade or refine the data used in the analyses. We also test whether differences in model performance are maintained at different sample sizes.Model performance improved when data processing and analytical methods addressed the challenges arising from citizen science data. The largest gains in model performance were achieved with: 1) the use of complete checklists (where observers report all the species they detect and identify); and 2) the use of covariates describing variation in effort and detectability for each checklist. Occupancy models were more robust to a lack of complete checklists and effort variables. Improvements in model performance with data refinement were more evident with larger sample sizes.Here, we describe processes to refine semi-structured citizen science data to estimate species distributions. We demonstrate the value of complete checklists, which can inform the design and adaptation of citizen science projects. We also demonstrate the value of information on effort. The methods we have outlined are also likely to improve other forms of inference, and will enable researchers to conduct robust analyses and harness the vast ecological knowledge that exists within citizen science data.

The migratory patterns of birds have been the focus of ecologists for millennia. What behavioural traits underlie these remarkably consistent movements? Addressing this question is central to advancing our understanding of migratory flight strategies and requires the integration of information across levels of biological organisation, e.g. species to communities. Here, we combine species-specific observations from the eBird citizen-science database with observations aggregated from weather surveillance radars during spring migration in central North America. Our results confirm a core prediction of migration theory at an unprecedented national scale: body mass predicts variation in flight strategies across latitudes, with larger-bodied species flying faster and compensating more for wind drift. We also find evidence that migrants travelling northward earlier in the spring increasingly compensate for wind drift at higher latitudes. This integration of information across biological scales provides new insight into patterns and determinants of broad-scale flight strategies of migratory birds.

Squamous cell carcinoma (SCC) of the neovagina after genital reconstruction surgery is a rare occurrence with only very few cases published up to the present. We report a case of a 43-year-old transgender woman who developed neovaginal SCC 23 years after vaginoplasty. The patient tested positive for high-risk human papillomavirus (HPV). At the time of diagnosis, radiological investigations revealed already existing lymph node and osseous metastases. The treatment consisted of various cycles of chemotherapy and radiation therapy. Unfortunately, the formation of additional metastases, including cerebral, pulmonary, and hepatic metastases, could not be prevented. After comparing the literature on the topic, we conclude that neovaginal carcinoma often appears years and decades after genital reconstruction surgery. We therefore recommend the continuation of regular clinical follow-up for transgender women after postoperative follow-up is completed. With this approach, potential lesions may be detected at an earlier stage and a better outcome may be achieved. Follow-up should include neovaginal examination and cytological smear testing. At a later age, we recommend additional regular prostate-specific antigen (PSA) testing and digital rectal examination (DRE). Moreover, transgender women are advised to take part in mammography screening starting at the age of 50, especially when additional risk factors are present.

Objectives: Asthma is a multifactorial, heterogeneous, complex and common chronic respiratory disease driven by diverse mechanisms. Although asthma presents various clinical forms with different levels of severity, it is unclear whether asthma severities are a consequence of disease management or varied etiologies. We sought to investigate this question. Methods: This article presents a cross-sectional study of 113,671 Israeli adolescents. Univariate and multivariable logistic regression models were performed to analyze the independent associations between mild asthma and moderate-to-severe asthma phenotypes and coexistent medical conditions within each gender separately. Hierarchical clustering of the odds ratios of the diverse statistically significant medical conditions associated with asthma severity-gender groups was also performed. We focused on the allergic and neurological-cognitive-mental disorders. Results: Among males, two associations were common to both asthma groups (atopic dermatitis and allergic rhinitis), five unique to mild asthma (urticaria/angioedema, Hymenoptera/bee allergies, allergic conjunctivitis, epilepsy and migraine) and two unique to moderate-to-severe asthma (learning disabilities and ADD/ADHD (Attention-deficit disorder/Attention-deficit/hyperactivity disorder)). Among females, two associations were common to both clinical asthma groups (allergic rhinitis and urticaria/angioedema), and five unique to moderate-to-severe asthma (atopic dermatitis, learning disabilities, ADD/ADHD, anxiety/mood disorders and migraine). Allergic rhinitis was the only condition to be associated with all four groups. Learning disabilities and ADD/ADHD were only associated with moderate-to-severe asthma (but not with mild asthma), in both males and females. Hierarchical clustering analysis uncovered two prominent clusters, separating mild from moderate-to-severe asthma. Conclusions: The differences between mild and moderate-to-severe asthma enhance asthma phenotype characterization, with respect to comorbidities, and indicate varied etiologies.

The words sound and noise are used interchangeably in acoustics, electronics, and physics, but have different connotations when applied to listeners. Sound is defined as vibrations that travel through air or another medium that can be heard when they reach a person’s or animal’s ears. Noise is defined as unwanted sound. In engineering, noise has the additional connotation of signals varying over time without meaning, whereas sound connotes meaningful signals. Unfortunately, the phrase unwanted sound implies that noise is merely a nuisance, ignoring what is now known about the harmful effects of noise on people and animals. It also implies a value judgment about noise, with a subjective component to the judgment of the listener complaining about noise. Often, there is an additional implication that those who complain about noise are neurotic, weak, self-centered, or have some other psychological or psychiatric problem that for them magnifies the impact of “harmless” sounds that don’t bother others. This latter implication is incorrect. Desired sounds can cause auditory damage, and unwanted sound is harmful. Evidence-based noise levels affecting human heath and function are well known. That is why I propose a new definition of noise: Noise is unwanted and/or harmful sound.

Most spatial conservation planning for wide-ranging or migratory species is constrained by poor knowledge of species' spatiotemporal dynamics and is only based on static species' ranges. However, species have substantial variation in abundance across their range and migratory species have important spatiotemporal population dynamics. With growing ecological data and advancing analytics, both of these can be estimated and incorporated into spatial conservation planning. However, there is limited information on the degree to which including this information affects conservation planning. We compared the performance of systematic conservation prioritizations for different scenarios based on varying the input species' distributions by ecological metric (abundance distributions versus range maps) and temporal sampling resolution (weekly, monthly, or quarterly). We used the example of a community of 41 species of migratory shorebirds that breed in North America, and we used eBird data to produce weekly estimates of species' abundances and ranges. Abundance distributions at a monthly or weekly resolution led to prioritizations that most efficiently protected species throughout the full annual cycle. Conversely, spatial prioritizations based on species' ranges required more sites and left most species insufficiently protected for at least part of their annual cycle. Prioritizations with only quarterly species ranges were very inefficient as they needed to target 40% of species' ranges to include 10% of populations. We highlight the high value of abundance information for spatial conservation planning, which leads to more efficient and effective spatial prioritization for conservation. Overall, we provide evidence that spatial conservation planning for wide-ranging migratory species is most robust and efficient when informed by species' abundance information from the full annual cycle.

We report an association between higher absolute nucleated red blood cells and mean corpuscular volume and idiopathic persistent pulmonary hypertension of the newborn in neonates with Down syndrome. Elevation of these blood indicies should prompt echocardiographic studies to monitor pulmonary arterial pressures.

That occupational noise exposure causes hearing loss has long been known, but non-occupational noise exposure was generally not recognized as causing hearing loss until the 1960s. Audiometric evaluation of populations not exposed to occupational noise was used to establish normal hearing baselines for workers compensation purposes. Audiometery in these groups, and in isolated populations not exposed to loud noise, suggested that hearing was preserved without noise exposure. The word sociocusis was used to describe non-occupational hearing loss. There are no federal recommendations, guidelines, or standards for non-occupational noise exposure. Perhaps because of a misconception that the 85 A-weighted decibel recommended occupational noise exposure limit is safe for the public without time limit, everyday noise exposure appears to have increased. Noise-induced hearing loss (NIHL) has become a major public health problem in the U.S., with approximately 20% of adolescents age 12–19 and 25% of adults age 20–69 having NIHL Common sources of non-occupational noise exposure include transportation noise, music and entertainment including personal listening devices, restaurant noise, kitchen appliances and power tools, hobbies, and sports. Efforts to reduce non-occupational noise exposure must include public education and the promulgation and enforcement of standards for non-occupational noise exposure.

Personal audio systems (PAS) are a major source of harmful noise doses, especially for children, teenagers, and young adults, who typically listen many hours daily at volumes exceeding the globally recommended public health limit of 70 dBA LEQ24h. PAS users increase listening volume to overcome high ambient noise. Research shows that (1) PAS use among people aged 9 + is associated with permanent, progressive hearing health disabilities including tinnitus, hyperacusis, speech communication impairments, and noise-induced hearing loss (NIHL); i(2) auditory health risk is highest for personal listening 1 + hours daily at over 50% volume with 5 + years of exposure; (3) clinical measures demonstrate noise-induced neural or retrocochlear auditory processing disorders precede sensory or cochlear impairments; and (4) children are highest risk because auditory system maturation is incomplete and normal hearing health is vital for learning, socialization, and vocational potential. Acquired hearing loss is associated with increased risk of accidents, communication difficulties, social isolation, and health impairments, including dementia in later life. Public health hearing conservation policies are needed to prevent an imminent NIHL epidemic in younger generations, including PAS noise emission standards and public education on the dangers of PAS use and about safer listening behaviors.

The seasonal dynamics of snow cover strongly affect ecosystem processes and winter habitat, making them an important driver of terrestrial biodiversity patterns. Snow cover data from the Moderate Resolution Imaging Spectroradiometer (MODIS) Aqua and Terra satellites can capture these dynamics over large spatiotemporal scales, allowing for the development of indices with specific application in ecological research and predicting biodiversity. Here, our primary objective was to derive winter habitat indices (WHIs) from MODIS that quantify snow season length, snow cover variability, and the prevalence of frozen ground without snow as a proxy for subnivium conditions. We calculated the WHIs for the full snow year (Aug-Jul) and winter months (Dec-Feb) across the contiguous US from 2003/04 to 2017/18 and validated them with ground-based data from 797 meteorological stations. To demonstrate the potential of the WHIs for biodiversity assessments, we modeled their relationships with winter bird species richness derived from eBird observations. The WHIs had clear spatial patterns reflecting both altitudinal and latitudinal gradients in snow cover. Snow season length was generally longer at higher latitudes and elevations, while snow cover variability and frozen ground without snow were highest across low elevations of the mid latitudes. Variability in the WHIs was largely driven by elevation in the West and by latitude in the East. Snow season length and frozen ground without snow were most accurately mapped, and had correlations with station data across all years of 0.91 and 0.85, respectively. Snow cover variability was accurately mapped for winter (r = 0.79), but not for the full snow year (r = −0.21). The model containing all three WHIs used to predict winter bird species richness patterns across the contiguous US was by far the best, demonstrating the individual value of each index. Regions with longer snow seasons generally supported fewer species. Species richness increased steadily up to moderate levels of snow cover variability and frozen ground without snow, after which it steeply declined. Our results show that the MODIS WHIs accurately characterized unique gradients of snow cover dynamics and provided important information on winter habitat conditions for birds, highlighting their potential for ecological research and conservation planning.

Heterobimetallic 1,4-divinylphenylene- and 1,8-divinylanthracene-bridged ruthenium/osmium complexes 1-RuOs and 2-RuOs were prepared via stepwise hydroruthenation of the parent dialkynes with first the ruthenium and then the osmium hydride complexes HM(CO)Cl(P i Pr 3 ) 2 . They are compared with their homobimetallic diruthenium and diosmium analogs with respect to their electrochemical and spectroscopic properties. Trends in redox potentials and changes in the vibrational and electronic spectra on oxidation point to strongly delocalized electronic ground states for the radical cations of the homobinuclear complexes and for heterobinuclear 1-RuOs + but a significant charge localization at the more electron-rich {Os} site for 2-RuOs + and a generally less efficient coupling of the alkenyl metal moieties to the π-conjugated bridge for the dinuclear 1,8-anthracenediyl complexes. The latter is due to a significant torsion of the alkenyl metal entities as a consequence of steric congestion around the closely spaced alkenyl ruthenium moieties as indicated by X-ray crystallography and by quantum chemical calculations.

Transoral laser microsurgery (TLM) has been increasingly used in lieu of total laryngectomy to treat malignancy after definitive radiation. There are few data in the literature regarding functional outcomes. We retrospectively reviewed voice and swallowing outcomes in patients who underwent TLM for recurrent laryngeal carcinoma.Case series with chart review.Tertiary care center.Forty-two patients were identified with recurrent squamous cell carcinoma of the larynx after definitive radiation therapy from 2001 to 2013: 28 patients with glottic recurrence and 14 with supraglottic recurrence. Swallowing outcomes were evaluated by gastrostomy tube dependence, the MD Anderson Dysphagia Inventory, and the Functional Oral Intake Scale. Voice outcomes were evaluated by the Voice Handicap Index and observer-rated perceptual analysis.No significant difference was noted between mean pre- and postoperative MD Anderson Dysphagia Inventory scores: 78.25 and 74.9, respectively (P = .118, t = 1.6955). Mean Functional Oral Intake Scale scores after TLM for supraglottic and glottic recurrences were 6.4 and 6.6, respectively. Of 42 patients, 17 (40.5%) required a gastrostomy tube either during radiation or in conjunction with the salvage procedure. Of 17 patients, 15 resumed sufficient oral diet for tube removal. Patients' mean Voice Handicap Index score did increase from 34.3 to 51.5 (P = .047), and their mean perceptual score did decrease from 60.0 to 45.3 (P = .005). However, at 1-year follow-up, there was no significant difference in perceptual score: 61.1 to 57.1 (P = .722).TLM is a successful surgical option for recurrent laryngeal cancer with acceptable functional outcomes.

Primary muscle tension dysphonia (PMTD) is a voice disorder of indeterminate cause, thought to be multifactorial. Emerging research is improving its diagnosis, but the lack of standard diagnostic testing for PMTD still creates challenges in accurate diagnosis and treatment. Review of the recent literature demonstrates the scarce validity and reliability of subjective laryngeal palpation measures, which are commonly used to assess the presence of intrinsic and extrinsic laryngeal tension in PMTD. An initial study with transcranial magnetic stimulation shows promise in the differential diagnosis between adductor spasmodic dysphonia and PMTD. Current and past review of the literature continues to demonstrate the need for future investigation to determine the true pathophysiology of PMTD and its accurate differential diagnosis.

ObjectiveThe aim of this study was to analyze the clinical experience and outcome of patients who have undergone pelvic exenteration for primary advanced or recurrent endometrial cancer.MethodsWe analyzed the medical records of 40 women who underwent pelvic exenteration to treat primary advanced or recurrent endometrial cancer.ResultsPelvic exenteration was performed in 40 patients with primary advanced or recurrent endometrial cancer. Three patients (8%) underwent a primary exenteration, and 37 patients (92%) underwent a secondary exenteration. A total exenteration, anterior exenteration, and posterior exenteration was performed in 85%, 5%, and 10% of patients, respectively.In 31 cases, exenteration was performed with a curative aim, and in 9 cases, exenteration was performed with a palliative aim. The overall survival rates were 61.4% at 5 years and 51.1% at 10 years. For the 31 patients who underwent pelvic exenteration with a curative aim, the overall survival rates were higher than those for the entire study population and were 72.6% at 5 years and 59.4% at 10 years. For the 9 patients who underwent a palliative exenteration, the overall survival rates were 19.1% at 5 years and 0% at 10 years. This is to the best of our knowledge the biggest study of pelvic exenteration in patients with endometrial cancer.ConclusionsOur data show that pelvic exenterations are a valid therapeutic option with long-term survival in select patients.

Micronized acellular dermis has been used for nearly 15 years to correct glottic insufficiency. With previous demonstration of safety and efficacy, this study aims to evaluate intermediate and long-term voice outcomes in those who underwent injection laryngoplasty for unilateral vocal fold paralysis. Technique and timing of injection were also reviewed to assess their impact on outcomes.Case series with chart review.Tertiary care center.Patients undergoing injection laryngoplasty from May 2007 to September 2012 were reviewed for possible inclusion. Pre- and postoperative Voice Handicap Index (VHI) scores, as well as senior speech-language pathologists' blinded assessment of voice, were collected for analysis. The final sample included patients who underwent injection laryngoplasty for unilateral vocal fold paralysis, 33 of whom had VHI results and 37 of whom had voice recordings. Additional data were obtained, including technique and timing of injection.Analysis was performed on those patients above with VHI and perceptual voice grades before and at least 6 months following injection. Mean VHI improved by 28.7 points at 6 to 12 months and 22.8 points at12 months (P = .001). Mean perceptual voice grades improved by 17.6 points at 6 to 12 months and 16.3 points at12 months (P.001). No statistically significant difference was found with technique or time to injection.Micronized acellular dermis is a safe injectable that improved both patient-completed voice ratings and blinded reviewer voice gradings at intermediate and long-term follow-up. Further investigation may be warranted regarding technique and timing of injection.

We aimed to investigate the mechanistic, functional, and therapeutic role of glycogen synthase kinase 3β (GSK-3β) in the regulation and activation of the proinflammatory oncogenic transcription factor nuclear factor of activated T cells (NFATc2) in pancreatic cancer. IHC, qPCR, immunoblotting, immunofluorescence microscopy, and proliferation assays were used to analyze mouse and human tissues and cell lines. Protein–protein interactions and promoter regulation were analyzed by coimmunoprecipitation, DNA pulldown, reporter, and ChIP assays. Preclinical assays were performed using a variety of pancreatic cancer cells lines, xenografts, and a genetically engineered mouse model (GEMM). GSK-3β–dependent SP2 phosphorylation mediates NFATc2 protein stability in the nucleus of pancreatic cancer cells stimulating pancreatic cancer growth. In addition to protein stabilization, GSK-3β also maintains NFATc2 activation through a distinct mechanism involving stabilization of NFATc2–STAT3 complexes independent of SP2 phosphorylation. For NFATc2–STAT3 complex formation, GSK-3β–mediated phosphorylation of STAT3 at Y705 is required to stimulate euchromatin formation of NFAT target promoters, such as cyclin-dependent kinase-6, which promotes tumor growth. Finally, preclinical experiments suggest that targeting the NFATc2–STAT3–GSK-3β module inhibits proliferation and tumor growth and interferes with inflammation-induced pancreatic cancer progression in KrasG12D mice. In conclusion, we describe a novel mechanism by which GSK-3β fine-tunes NFATc2 and STAT3 transcriptional networks to integrate upstream signaling events that govern pancreatic cancer progression and growth. Furthermore, the therapeutic potential of GSK-3β is demonstrated for the first time in a relevant Kras and inflammation-induced GEMM for pancreatic cancer. Mol Cancer Ther; 15(3); 491–502. ©2016 AACR.

Zusammenfassung. Endometriose ist eine häufige benigne Erkrankung der Frau in der reproduktiven Phase. Sie manifestiert sich zumeist mit schwerer Dysmenorrhö, chronischen Unterbauchschmerzen und Dyspareunie, ist aber häufig auch mit Sterilität assoziiert. Die genaue Pathogenese ist bis heute nicht restlos geklärt, sodass therapeutisch derzeit eher symptomorientiert als kausal behandelt wird. Der folgende Artikel soll eine Übersicht über die derzeitigen Diagnose- und Behandlungsmethoden dieser rätselhaften Erkrankung geben.

Objective To assess the efficacy of laryngeal mask airway (LMA) ventilation in obese patients with airway stenosis. Study Design A retrospective chart review was conducted in an academic practice in a tertiary care center. Methods We retrospectively reviewed our experience using LMA ventilation in obese patients with airway stenosis. Lowest intraoperative O2 saturation and maximum-end tidal carbon dioxide (CO2) levels were recorded. Complications including intubation, unplanned admission, re-admission, postoperative pain, dysphonia, oral trauma, pneumothorax, pneumomediastinum, and tracheostomy were recorded. Results Fourteen bronchoscopies with laser incisions and dilation were performed in patients with airway stenosis exclusively using LMA ventilation. Thirteen of 14 procedures were performed on patients who had body mass index (BMI) > 30 kg/m2. Mean BMI was noted to be 38 kg/m2 (range 25–54). All patients underwent successful laser incisions and dilation via LMA anesthesia without major or minor adverse events. The mean lowest O2 saturation level was noted to be 92%; the mean highest CO2 level was noted to be 56 mm Hg; and no patients required endotracheal intubation. Conclusion In this small series of obese patients with airway stenosis, LMA anesthesia was effectively used without major or minor complications. Level of Evidence 4. Laryngoscope, 2017

Chlamydia trachomatis is the most common bacterial cause of sexually transmitted disease and can cause pelvic inflammatory disease (PID), leading to severe outcomes such as ectopic pregnancy, infertility, or pelvic pain. We report a case of a 38-year-old patient with abdominal pain and dyspareunia. Clinical examination revealed diffuse abdominal tenderness. Vaginal and abdominal sonography showed substantial ascites and CA-125 level was elevated. Therefore, the attendant physician performed an abdominal CT scan for further diagnosis. Radiographically diffuse peritoneal enhancement, consistent with peritoneal carcinomatosis, 4-quadrant ascites, and slightly enlarged ovaries with solid and cystic structures were diagnosed, leading to the suspicion of ovarian cancer. In addition, the results of the cervical smear PCR for chlamydia were positive. Due to the positive chlamydia result, the suspicious CT scan, and the young age, we decided to perform a diagnostic laparoscopy as a first step. Intraoperatively, the ovaries were of normal aspect without any cancerous lesions. However, the ascites and the yellow-reddish jelly-like deposits were consistent with acute PID. Thus, chlamydia infection may simulate the presentation of ovarian cancer. Therefore, especially in young patients, we recommend careful scrutiny of every diagnosis of ovarian cancer even if its presentation seems to be typical.

Ibrutinib is an orally available, small-molecule tyrosine kinase inhibitor. Its main purpose is to inhibit Bruton’s tyrosine kinase (BTK), an enzyme that is crucial in B cell development. It is FDA approved for the treatment of certain hematological malignancies. Several promising off-target drug effects have led to multiple, mostly preclinical investigations regarding its use in solid tumors. Unfortunately, data on its effectiveness in gynecological malignancies are limited, and (systematic) reviews are missing. The objective of this review was to summarize the existing literature and to analyze the evidence of ibrutinib as a treatment option in gynecological malignancies, including breast cancer. Studies were identified in MEDLINE and EMBASE using a defined search strategy, and preclinical or clinical research projects investigating ibrutinib in connection with these malignancies were considered eligible for inclusion. Our findings showed that preclinical studies generally confirm ibrutinib’s efficacy in cell lines and animal models of ovarian, breast, and endometrial cancer. Ibrutinib exerts multiple antineoplastic effects, such as on-target BTK inhibition, off-target kinase inhibition, and immunomodulation by interference with myeloid-derived suppressor cells (MDSCs), programmed death-ligand 1 (PD-L1), and T cell response. These mechanisms were elaborated and discussed in the context of the evidence available. Further research is needed in order to transfer the preclinical results to a broader clinical appliance.

Ecological citizen science data are rapidly growing in availability and use in ecology and conservation. Many citizen science projects have the flexibility for participants to select where they survey, resulting in more participants, but also spatially biased data. It is important to assess the extent to which these spatially biased data can provide reliable estimates of species distributions. Here we quantify the extent of site selection bias in a citizen science project and the implications of this spatial bias in species distribution models. Using data from the BirdTrack citizen science project in Great Britain from 2007 to 2011, we modelled the spatial bias of data submissions. We next produced species occupancy models for 138 bird species, and assessed the impact of accounting for spatial bias. We compared the distributions to those produced using unbiased data from an Atlas survey from the same region and time period. Averaging across 138 species, models with spatially biased data produced accurate and precise estimates of species occupancy for most locations in Great Britain. However, these distributions were both less accurate and less precise in the Scottish Highlands, showing on average a positive bias. Accounting for the spatially biased sampling with weights led to on average greater accuracy in the Scottish Highlands, but did not increase precision. This region is both distinct in environmental characteristics and has a low density of observations, making it difficult to characterise environmental relationships with species occupancy. Accounting for the spatially biased sampling did not affect average accuracy or precision throughout most of the country. Spatially biased citizen science data can be used to estimate species occupancy in regions with stationary environmental relationships and good sampling across environmental space. The reliability of estimated species distributions from spatially biased data should be further validated and tested under a range of different scenarios.

Importance Surgical treatment comparisons in rare diseases are difficult secondary to the geographic distribution of patients. Fortunately, emerging technologies offer promise to reduce these barriers for research. Objective To prospectively compare the outcomes of the 3 most common surgical approaches for idiopathic subglottic stenosis (iSGS), a rare airway disease. Design, Setting, and Participants In this international, prospective, 3-year multicenter cohort study, 810 patients with untreated, newly diagnosed, or previously treated iSGS were enrolled after undergoing a surgical procedure (endoscopic dilation [ED], endoscopic resection with adjuvant medical therapy [ERMT], or cricotracheal resection [CTR]). Patients were recruited from clinician practices in the North American Airway Collaborative and an online iSGS community on Facebook. Main Outcomes and Measures The primary end point was days from initial surgical procedure to recurrent surgical procedure. Secondary end points included quality of life using the Clinical COPD (chronic obstructive pulmonary disease) Questionnaire (CCQ), Voice Handicap Index-10 (VHI-10), Eating Assessment Test-10 (EAT-10), the 12-Item Short-Form Version 2 (SF-12v2), and postoperative complications. Results Of 810 patients in this cohort, 798 (98.5%) were female and 787 (97.2%) were white, with a median age of 50 years (interquartile range, 43-58 years). Index surgical procedures were ED (n = 603; 74.4%), ERMT (n = 121; 14.9%), and CTR (n = 86; 10.6%). Overall, 185 patients (22.8%) had a recurrent surgical procedure during the 3-year study, but recurrence differed by modality (CTR, 1 patient [1.2%]; ERMT, 15 [12.4%]; and ED, 169 [28.0%]). Weighted, propensity score–matched, Cox proportional hazards regression models showed ED was inferior to ERMT (hazard ratio [HR], 3.16; 95% CI, 1.8-5.5). Among successfully treated patients without recurrence, those treated with CTR had the best CCQ (0.75 points) and SF-12v2 (54 points) scores and worst VHI-10 score (13 points) 360 days after enrollment as well as the greatest perioperative risk. Conclusions and Relevance In this cohort study of 810 patients with iSGS, endoscopic dilation, the most popular surgical approach for iSGS, was associated with a higher recurrence rate compared with other procedures. Cricotracheal resection offered the most durable results but showed the greatest perioperative risk and the worst long-term voice outcomes. Endoscopic resection with medical therapy was associated with better disease control compared with ED and had minimal association with vocal function. These results may be used to inform individual patient treatment decision-making.

The presence of natural light in indoor spaces improves human health, well-being, and productivity, particularly in workplace environments. Do the social benefits of daylight translate into economic value as measured by what office tenants are willing to pay? Using a sample of 5154 office spaces in Manhattan, we pair urban daylight simulation with a hedonic valuation model to determine the marginal value of daylight in offices. Holding all other factors constant, we find that occupied spaces with access to high amounts of daylight (as measured by 55% spatial daylight autonomy) have a 5–6% value premium over occupied spaces with low amounts of daylight (as measured by less than 55% spatial daylight autonomy). We simulate the distribution of daylight on each office floor individually, taking into account architectural and location-specific characteristics. Then, using the hedonic model, we determine the added value of daylight in the office spaces. The results show, for the first time, that an estimated 74% of office spaces throughout Manhattan have low daylight, and that in a dense urban environment with differentiation in daylight levels, tenants value high daylight. Daylight value is independent of other building, neighborhood, and contract characteristics. By revealing the added value of daylight in commercial office spaces, we suggest that daylight is a key design driver and thus, should be considered in design, policy, planning, and project financing.

BACKGROUND: Dysphagia is common in hospitalized patients post-extubation and associated with poor outcomes. Laryngeal sensation is critical for airway protection and safe swallowing. However, current understanding of the relationship between laryngeal sensation and aspiration in post-extubation populations is limited. METHODS: Acute respiratory failure patients requiring intensive care unit admission and mechanical ventilation received a Flexible Endoscopic Evaluation of Swallowing (FEES) within 72 hours of extubation. Univariate and multivariable analyses were performed to examine the relationship between laryngeal sensation, length of intubation, and aspiration. Secondary outcomes included pharyngolaryngeal secretions, pneumonia, and diet recommendations. RESULTS: One-hundred and three patients met inclusion criteria. Fifty-one patients demonstrated an absent laryngeal adductor reflex (LAR). Altered laryngeal sensation correlated with the presence of secretions (p = 0.004). There was a significant interaction between the LAR, aspiration, and duration of mechanical ventilation. Altered laryngeal sensation was significantly associated with aspiration on FEES only in patients with a shorter length of intubation (p = 0.008). Patients with altered laryngeal sensation were prescribed significantly more restricted liquid (p = 0.03) and solid (p = 0.001) diets. No relationship was found between laryngeal sensation and pneumonia. CONCLUSIONS: There is a high prevalence of laryngeal sensory deficits in mechanically ventilated patients post-extubation. Altered laryngeal sensation was associated with secretions, aspiration, and modified diet recommendations especially in those patients with a shorter length of mechanical ventilation. These results demonstrate that laryngeal sensory abnormalities impact the development of post-extubation dysphagia.

In mitosis, cells inactivate DNA double-strand break (DSB) repair pathways to preserve genome stability. However, some early signaling events still occur, such as recruitment of the scaffold protein MDC1 to phosphorylated histone H2AX at DSBs. Yet, it remains unclear whether these events are important for maintaining genome stability during mitosis. Here, we identify a highly conserved protein-interaction surface in MDC1 that is phosphorylated by CK2 and recognized by the DNA-damage response mediator protein TOPBP1. Disruption of MDC1-TOPBP1 binding causes a specific loss of TOPBP1 recruitment to DSBs in mitotic but not interphase cells, accompanied by mitotic radiosensitivity, increased micronuclei, and chromosomal instability. Mechanistically, we find that TOPBP1 forms filamentous structures capable of bridging MDC1 foci in mitosis, indicating that MDC1-TOPBP1 complexes tether DSBs until repair is reactivated in the following G1 phase. Thus, we reveal an important, hitherto-unnoticed cooperation between MDC1 and TOPBP1 in maintaining genome stability during cell division.

Introduction and hypothesis: The aim of the Incontinence Outcome Questionnaire (IOQ) is to assess quality of life and patient-reported outcome after midurethral slings. Methods: In this retrospective study, 626 patients with a minimum follow-up period of 1year were sent the IOQ. Four hundred twenty-two of 626 (67.4%) patient responses were evaluated. Results: The mean IOQ QoL extended score was 33.7 ± 17.5 and comparable for tension-free vaginal tape (TVT), outside-in transobturator tape (TOT), and inside-out transobturator vaginal tape (TVT-O). Evaluation of IOQ question about readmission revealed a total of 32 patients (18 TVT, 12 TOT, and 2 TVT-O) who underwent a subsequent operation due to sling-related complications. Freedom from reoperation for recurrent SUI at 1, 2, and 5years was 100%, 99.7 ± 0.3%, and 99.7 ± 0.3% for TVT, 100% for TVT-O, and 94.2 ± 2.5%, 91.9 ± 2.9%, and 89.9 ± 3.5% for TOT, respectively (p

While many observations of species are being collected by citizen science projects worldwide, it can be challenging to identify projects collecting data that effectively monitor biodiversity. Over the past several years the allure of taking a “Big Data” approach has provided the opportunity to gather massive quantities of observations via the Internet, too often with insufficient information to describe how the observations were made. Information about species populations — where and when they occur and how many of them are there — (i.e., the signal) can be lost because insufficient information is gathered to account for the inherent biases in data collection (i.e., the noise). Here we suggest that citizen science projects that have succeeded in motivating large numbers of participants, must consider factors that influence the ecological process that affect species populations as well as the observation process that determines how observations are made. Those citizen science projects that collect sufficient contextual information describing the observation process can be used to generate increasingly accurate information about the distribution and abundance of organisms. We illustrate this using eBird as a case study, describing how this citizen science platform is able to collect vital contextual information on the observation process while maintaining a broad global constituency of participants. We highlight how eBird provides information with which to generate biodiversity indicators — specifically distribution, abundance, and habitat associations — across the entire annual cycle, even for populations of long distance migratory birds, a highly challenging taxon.

Analysis of animal population status and change are core elements of ecological research and critical for prioritizing conservation actions. Traditionally, count-based data from structured surveys have been the main source of information used to estimate trends and changes in populations. In the past decade, advances in integrated population models (IPMs) have allowed these data to be combined with other data sources (e.g., observations of marked individuals). IPMs have allowed researchers to determine the direction and magnitude of a species' population trajectory and to test underlying mechanisms. For many species, life-history characteristics (e.g., low site-fidelity), low abundance and/or low detection probability make it difficult to collect sufficient data; thus, IPMs for these species are difficult to employ. We used count data from eBird to estimate population trends for one such species, the tricolored blackbird (Agelaius tricolor). We combined estimates of relative abundance with banding and nesting data. Our joint estimation of demographic rates allowed us to evaluate their individual contributions to the population growth rate. We suggest that investments in increasing reproductive success and recruitment are the most likely conservation strategies to increase the population. The extensive survey efforts of citizen scientists aided the employment of IPMs to inform conservation efforts.

Limited knowledge of the distribution, abundance, and habitat associations of migratory species hinders effective conservation actions. We use Neotropical migratory birds as a model group to compare approaches to prioritize land conservation needed to support ≥30% of the global abundances of 117 species. Specifically, we compare scenarios from spatial optimization models to achieve conservation targets by: 1) area requirements for conserving >30% abundance of each species for each week of the year independently vs. combined; 2) including vs. ignoring spatial clustering of species abundance; and 3) incorporating vs. avoiding human-dominated landscapes. Solutions integrating information across the year require 56% less area than those integrating weekly abundances, with additional reductions when shared-use landscapes are included. Although incorporating spatial population structure requires more area, geographical representation among priority sites improves substantially. These findings illustrate that globally-sourced citizen science data can elucidate key trade-offs among opportunity costs and spatiotemporal representation of conservation efforts., Conservation decisions to protect land used by migratory birds rely on understanding species’ dynamic habitat associations. Here the authors identify conservation scenarios needed to maintain >30% of the abundances of 117 migratory birds across the Americas, considering spatial and temporal patterns of species abundance.

Avian migration is one of Earth's largest processes of biomass transport, involving billions of birds. We estimated continental biomass flows of nocturnal avian migrants across the contiguous United States using a network of 143 weather radars. We show that, relative to biomass leaving in autumn, proportionally more biomass returned in spring across the southern United States than across the northern United States. Neotropical migrants apparently achieved higher survival during the combined migration and non-breeding period, despite an average three- to fourfold longer migration distance, compared with a more northern assemblage of mostly temperate-wintering migrants. Additional mortality expected with longer migration distances was probably offset by high survival in the (sub)tropics. Nearctic-Neotropical migrants relying on a 'higher survivorship' life-history strategy may be particularly sensitive to variations in survival on the overwintering grounds, highlighting the need to identify and conserve important non-breeding habitats.

Determining the implications of global climate change for highly mobile taxa such as migratory birds requires a perspective that is spatiotemporally comprehensive and ecologically relevant. Here, we document how passerine bird species that migrate within the Western Hemisphere (n = 77) are associated with projected novel climates across the full annual cycle. Following expectations, highly novel climates occurred on tropical non-breeding grounds and the least novel climates occurred on temperate breeding grounds. Contrary to expectations, highly novel climates also occurred within temperate regions during the transition from breeding to autumn migration. This outcome was caused by lower inter-annual climatic variability occurring in combination with stronger warming projections. Thus, migrants are projected to encounter novel climates across the majority of their annual cycle, with a pronounced peak occurring when juveniles are leaving the nest and preparing to embark on their first migratory journey, which may adversely affect their chances of survival.

Background The role of somatic BRCA1/2 gene mutations in breast cancer is getting increasing attention in view of hereditary disease. The medullary phenotype and triple negative intrinsic subtypes are often, but not exclusively encountered in BRCA1 germline mutated breast cancer, whilst for BRCA2, no association to specific histological features are known. In this study, we addressed the relationship between morphological medullary phenotype and BRCA1/2 somatic mutations in breast cancer without known positive family anamnesis. Methods 32 clinically sporadic breast cancers with medullary features were analyzed for somatic BRCA1/2 mutations (all coding exons) with next-generation sequencing technology. Paraffin-embedded formalin-fixed breast cancer samples from all patients were analyzed. Results Three of 32 tumors (9%) had pathogenic (ARUP class-5) BRCA1 gene alterations. Two of these pathogenic variants exhibited deletions leading to frameshift mutations (p.Glu23fs, p.Val1234fs), and the remaining single-nucleotid-variant resulted in premature STOP codon (p.Glu60Ter). In one patient, the same pathogenic BRCA1 mutation was detected (p.Glu23fs) in normal breast tissue. Retrospective follow-up in two patients revealed a positive family history for breast cancer and consecutive germline mutation testing confirmed presence of BRCA1 mutations. No somatic pathogenic BRCA2 mutations were detected. Conclusions BRCA1 mutation testing may be useful in clinically sporadic breast cancer patients with medullary features to identify potential mutation carriers independently from intrinsic molecular subtype. Formalin-fixed paraffin-embedded cancer tissue can undergo testing within a routine molecular-diagnostic setting as a clinical BRCA1/2 mutation screening strategy.

"Rebuild Palmyra?" is a multimedia exhibition about the ancient city of Palmyra, its destruction by Daesh, and the question of whether it should be rebuilt. As such, it tackles today's pressing question of how humanity should deal with the destruction of cultural heritage. In the design of the exhibition, we pursued the Blended Museum approach, in which we strive to seamlessly integrate interactive media into exhibition design to increase the overall visitor experience. In this work, we present the exhibition, which consists of four rooms. We focus on three interactive installations in which the topic of reconstructing Palmyra is mediated using new technologies such as 3D Printing, Augmented Reality, and Virtual Reality. The installations helped visitors in developing their own point of view on the question of rebuilding Palmyra. Lastly, we provide insights into the technical implementation of the installations and discuss the results of quantitative and qualitative evaluations. published

Little is known about the mechanical properties of pelvic floor structures and their role in the course and treatment of pelvic organ prolapse (POP). We hypothesize that in vivo mechanical properties of the vaginal wall are related to the appearance of POP and pre-and post-operative states. We used a suction device for intravaginal application, the aspiration device, to evaluate two in vivo mechanical parameters of the anterior vaginal wall, the load dependent tissue displacement and the initial displacement, by image analysis in pre- and post-menopausal women with (POP) and without (control) cystocele (POP: pre-menopausal: N = 6, post-menopausal: N = 19, control: pre-menopausal: N = 17, post-menopausal: N = 6). Mechanical parameters in women with and without cystocele and pre- and post-operative parameters were compared. Statistically significant differences were observed between the two mechanical parameters in pre- and post-operative states (P = 0.04, P = 0.03), but not between the parameters for women with and without cystocele (P = 0.92, P = 0.75). The mechanical behavior of pelvic floor structures is influenced by factors such as POP, age or estrogenization that are apparent at different length scales, which cannot be separated by the aspiration based biomechanical measurements. When comparing pre- and post-operative states of the same patient, a firmer tissue response was observed after intervention., Scientific Reports, 7 (1), ISSN:2045-2322

In the era of precision medicine, the tailoring of cancer treatment is increasingly important as we transition from organ-based diagnosis towards a more comprehensive and patient-centric molecular diagnosis. This is particularly the case for high-grade serous adenocarcinomas of the ovary and peritoneum, which are commonly diagnosed at an advanced stage, and collectively treated and managed similarly. We characterized the N- and O-glycome of serous ovarian (OC) and peritoneal cancer (PC) tissues using PGC-LC-ESI-IT-MS/MS profiling and validated the discriminatory glycans and their corresponding glyco-gene expression levels using cell lines and transcriptomic data from 232 patients. Overall, the N- and O-glycan repertoires of both cancer types were found to comprise mostly of α2,6-sialylated glycan structures, with the majority of N-glycans displaying the biantennary mono- and disialylation as well as bisecting-type biantennary glycans. The MS profiling by PGC-LC also revealed several glycan structural isomers that corresponded to LacdiNAc-type (GalNAcβ1-4GlcNAc) motifs that were unique to the serous ovarian cancers and that correlated with elevated gene expression of B4GALNT3 and B4GALNT4 in patients with serous cancer. Statistical evaluation of the discriminatory glycans also revealed 13 N- and 3 O-glycans (P

Data from well-designed experiments provide the strongest evidence of causation in biodiversity studies. However, for many species the collection of these data is not scalable to the spatial and temporal extents required to understand patterns at the population level. Only data collected from citizen science projects can gather sufficient quantities of data, but data collected from volunteers are inherently noisy and heterogeneous. Here we describe a ‘Big Data’ approach to improve the data quality in eBird, a global citizen science project that gathers bird observations. First, eBird’s data submission design ensures that all data meet high standards of completeness and accuracy. Second, we take a ‘sensor calibration’ approach to measure individual variation in eBird participant’s ability to detect and identify birds. Third, we use species distribution models to fill in data gaps. Finally, we provide examples of novel analyses exploring population-level patterns in bird distributions.

Vuval pathologies manifested by allodynia and burning sensations can be due to infection, inflammatory dermatoses or other causes. Infective as well as certain inflammatory diseases, e.g. drug eruptions, allergic eczemas, irritative dermatitis/vulvitis, Behcet's Syndrome and pemphigus/pemphigoid usually respond well to conservative treatment. The category of inflammatory diseases also contains pathologies that in certain circumstances do require a surgical intervention, e.g. Lichen ruber planus/Lichen sclerosus, Condyloma, scars, premalignant lesions (VIN, genital M. Paget) and cancer. Vulodynia also can cause some stinging to the vulvar skin. The surgical aspects relating to the treatment of the benign and premalignant pathologies indicated above are mentioned in this mini-review.

Background Pharyngocutaneous fistula (PCF) is a common and challenging complication of laryngectomy. The purpose of this study was to evaluate the results of endoscopic repair of postlaryngectomy PCF. Methods Five patients who underwent salvage laryngectomy complicated by PCF underwent endoscopic repair at a regional medical center between 2006 and 2013. Data were compiled through a manual chart review and demographic data, adjuvant treatment, comorbidities, and clinical course were all recorded. Results Five patients underwent endoscopic repair of PCF. All patients had previously received radiation or chemoradiation therapy and underwent salvage total laryngectomy. The mean number of days to resumption of oral intake after endoscopic repair was 22 days. One patient required reoperation. No complications were noted. Conclusion Endoscopic suture repair can be an effective method for treating PCF with less morbidity than flap reconstruction or conservative wound management. © 2014 Wiley Periodicals, Inc. Head Neck 37: E81–E84, 2015

Die Frühschwangerschaft umfasst das 1. Trimenon und somit die Zeitspanne zwischen Konzeption und Abschluss der 12. SSW mit der embryonalen Implantation und Organogenese. Als gestört gilt eine Frühschwangerschaft, wenn sich der Embryo nicht korrekt intrauterin einnistet (extrauterine Gravidität EUG), sich nicht regelrecht (missed abortion) oder gar nicht (Windmole) entwickelt und es früher oder später zum Abort kommt. Als Spezialfall ist der «vanishing twin», als eine Form der missed abortion im Rahmen einer ursprünglichen Zwillingsschwangerschaft zu nennen. Selten kommt es zudem zu gestationsbedingten Trophoblasterkrankungen mit einer kompletten (keine fetalen Anteile) oder inkompletten (fetale Anteile nachweisbar) Blasenmole und den invasiven Molen als villöse Trophoblasterkrankungen sowie den nicht-villösen Trophoblasterkrankungen mit dem seltenen Chorionkarzinom.

Zusammenfassung. Die interstitielle Zystitis, heute als Bladder Pain Syndrome bezeichnet (BPS), ist ein ätiologisch unverstandenes chronisches Schmerzsyndrom. Die Diagnose fusst auf der Klinik. Die heutigen Therapiemodalitäten zielen auf die Symptomlinderung ab, da keine Heilung möglich ist. Analgetika sind vor allem punktuell einzusetzen. Das sechsstufige Therapieprogram der AUA beginnt mit der nicht-invasiven und nebenwirkungsarmen Verhaltenstherapie, Patientenaufklärung und psychosozialer Unterstützung. Bei Beckenbodenverspannungen kann in einer zweiten Stufe Physiotherapie verordnet werden. Als orale Medikamente helfen Amitriptylin, PPS oder Antihistaminika. Die interventionelle Zystoskopie mit Hydrodistension kommt als dritte Stufe zum Zug. Erst bei Persistenz der Beschwerden werden Neuromodulation (vierte Stufe), intravesikale Botoxinjektionen (fünfte Stufe) oder Cyclosporin A eingesetzt. Als Ultima Ratio gilt die sechste Stufe mit der Zystektomie als invasivste und definitive Lösung.