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Objective Despite advances in health care and ample resources, post-partum hemorrhage (PPH) rates are increasing in high income countries. Although guidelines recommend therapeutic uterotonics, timing of administration is open to judgement and most often based on (inherently inaccurate) visual estimates of blood loss. With severe hemorrhage, every minute of delay can have significant consequences. Our objective was to examine the timing of uterotonic administration and its impact upon maternal outcomes. We hypothesized that increased time to uterotonic administration following the identification of PPH, would be associated with a greater decline in hemoglobin (Hb) and higher odds of hypotension and transfusion. Methods We reviewed all cases of PPH that occurred at an academic centre between June 2015 and September 2017. All cases of primary PPH (i.e., those declared within 24 h of delivery with estimated blood loss [EBL] >500 mL for vaginal and >1000 mL for cesarean deliveries) were analyzed. Patient records were excluded if they were missing information regarding time of PPH declaration, uterotonic administration, and/or Hb measures, or if a pre-existing medical condition could have contributed to PPH. Results Of 4397 births, there were 259 (5.9%) cases of primary PPH, of which 128 were included in this analysis. For these patients, each 5-minute delay in uterotonic treatment was associated with 26% higher odds of hypotension following delivery of any type. For vaginal deliveries (n = 86), each 5-minute delay was associated with 31% and 34% higher odds of hypotension and transfusion, respectively. Conclusion In this study, delay in administration of therapeutic uterotonics was associated with a higher incidence of hypotension and transfusion in primary PPH patients.

Context Low-intensity shockwave therapy (LiST) has emerged as an effective treatment for pain in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and it has been postulated that LiST may also be effective in patients with lower urinary tract symptoms (LUTS). Objective To perform a systematic review and meta-analysis of experimental and clinical studies exploring the effect of LiST on LUTS in an attempt to provide clinical implications for future research. Evidence acquisition We systematically searched PubMed, Cochrane Library, and Scopus databases from inception to March 2021 for relevant studies. We provided a qualitative synthesis regarding the role of LiST in LUTS and performed a single-arm, random-effect meta-analysis to assess the absolute effect of LiST on LUTS only in patients with CP/CPPS (PROSPERO: CRD42021238281). Evidence synthesis We included 23 studies (11 experimental studies, seven nonrandomized controlled trials [non-RCTs], and five RCTs) in the systematic review and seven in the meta-analysis. All experimental studies were performed on rats with LUTS, and the clinical studies recruited a total of 539 participants. In patients with CP/CPPS, the absolute effect of LiST on maximum flow rate and postvoid residual was clinically insignificant. However, the available studies suggest that LiST is effective for the management of pain in patients with either CP/CPPS or interstitial cystitis/bladder pain syndrome. Additionally, LiST after intravesical instillation of botulinum neurotoxin type A may enhance its absorption and substitute botulinum neurotoxin type A injections in patients with overactive bladder. Furthermore, the available evidence is inconclusive about the role of LiST in patients with benign prostatic obstruction, stress urinary incontinence, or underactive bladder/detrusor hypoactivity. Conclusions LiST may be effective for some disorders causing LUTS. Still, further studies on the matter are necessary, since the available evidence is scarce. Patient summary Low-intensity shockwave therapy represents a safe, easily applied, indolent, and repeatable on an outpatient basis treatment modality that may improve lower urinary tract symptoms.

2D LiDAR is an efficient alternative sensor for vehicle detection, which is one of the most critical tasks in autonomous driving. Compared to the fully-developed 3D LiDAR vehicle detection, 2D LiDAR vehicle detection has much room to improve. Most of existing state-of-the-art works represent 2D point clouds as pseudo-images and then perform detection with traditional object detectors on 2D images. However, they ignore the sparse representation and geometric information of vehicle in the 2D cloud points. In this paper, we present Keypoint-Aware and Keypoint-Matching Network termed as KAM-Net, specifically focus on better detecting the vehicles by explicitly capturing and extracting the sparse information of L-shape in 2D LiDAR point clouds. The whole framework consists of two stages, namely keypoint-aware stage and keypoint-matching stage. The keypoint-aware stage utilizes the heatmap and edge extraction module to simultaneously predict the position of L-shaped keypoints and inflection offset of L-shaped endpoints. The keypoint-matching stage is followed to group the keypoints and produces the oriented bounding boxes with axis by utilizing the endpoint-matching and Lshaped-matching methods. Further, we conduct extensive experiments on a recently released public dataset to evaluate the effectiveness of our approach. The results show that our KAM-Net achieves a new state-of-the-art performance.

Although great progress has been made in generic object detection by advanced deep learning techniques, detecting small objects from images is still a difficult and challenging problem in the field of computer vision due to the limited size, less appearance, and geometry cues, and the lack of large-scale datasets of small targets. Improving the performance of small object detection has a wider significance in many real-world applications, such as self-driving cars, unmanned aerial vehicles, and robotics. In this article, the first-ever survey of recent studies in deep learning-based small object detection is presented. Our review begins with a brief introduction of the four pillars for small object detection, including multiscale representation, contextual information, super-resolution, and region-proposal. Then, the collection of state-of-the-art datasets for small object detection is listed. The performance of different methods on these datasets is reported later. Moreover, the state-of-the-art small object detection networks are investigated along with a special focus on the differences and modifications to improve the detection performance comparing to generic object detection architectures. Finally, several promising directions and tasks for future work in small object detection are provided. Researchers can track up-to-date studies on this webpage available at: https://github.com/tjtum-chenlab/SmallObjectDetectionList.

BACKGROUND Airway release (AR) maneuvers performed during airway resection to reduce anastomotic tension have not been thoroughly studied. METHODS This study retrospectively analyzed consecutive resections for postintubation stenosis (PITS) and primary tracheal neoplasms (PTNs) at Massachusetts General Hospital (Boston, MA). Anastomotic complications were defined as stenosis, separation, necrosis, granulation tissue, and air leak. Logistic regression modeling was used to identify factors associated with AR and adverse outcome. RESULTS From 1993 to 2019, 545 patients with PITS (375; 68.8%) and PTNs (170; 31.2%) underwent laryngotracheal, tracheal, or carinal (resections and reconstructions; 5.7% (31 of 545) were reoperations. AR was performed in 11% (60 of 545): in 3.8% of laryngotracheal resections (6 of 157; all laryngeal), in 9.8% of tracheal resections (34 of 347; laryngeal, 12, and hilar, 22), and in 49% of carinal resections (20 of 41; laryngeal, 1, and hilar, 19). Mean resected length was 3.5 cm (range, 1to- 6.3 cm) with AR and 3.0 cm (range, 0.8 to 6.5 cm) without AR (P < .01). Operative mortality was 0.7% (4 of 545); all 4 anastomoses were intact until death. Anastomotic complications were present in 5% of patients who underwent AR (3 of 60) and in 9.3% (45 of 485) of patients who did not. AR was associated with resection length of 4 cm or longer (odds ratio [OR], 6.15; 95% confidence interval [CI], 1.37 to 27.65), PTNs (OR, 7.81; 95% CI, 3.31 to 18.40), younger age (OR, 0.96; 95% CI, 0.94 to 0.98), and lung resection (OR, 6.09; 95% CI, 1.33 to 27.90). Anastomotic complications in patients with tracheal anastomoses were associated with preexisting tracheostomy (OR, 2.68; 95% CI, 1.50 to 4.80), but not release. CONCLUSIONS Tracheal reconstruction succeeds, even when anastomotic tension requires AR. Because intraoperative assessment may underestimate tension, lowering the threshold for AR seems prudent, particularly in patients with diabetes.

We introduce a new approach for glucose oxidase (GOx) immobilization on graphene field-effect transistors (gFETs) to fabricate highly sensitive glucose sensors. The strategy relies on the electropolymerization of a layer of the copolymer poly(3-amino-benzylamine-co-aniline) (PABA) on graphene-based transistors. The synthesized polymer film provides the suitable electrostatic charge and non-denaturing environment for enzyme immobilization without the need of any chemical primer. Then, the local pH changes triggered by the enzyme-catalyzed oxidation produce a shift in the Dirac potential of the gFETs to more negative values, which is evidenced by the differences in the graphene channel conductivity and constitutes the signal transduction mechanism of the sensing devices. The assembled biosensors revealed a low LOD of 4.1 μM and were capable of detecting glucose in the range from 10 to 1000 μM in a flow configuration. Moreover, they showed sensitivity of −24.9 μA per decade of glucose concentration and a fast response time, with an average value of 190 seconds, while allowing the operation at small gate-source and drain-source voltages. Finally, the biosensors were able to successfully monitor the analyte in urine samples, showing their potential towards the fabrication of point-of-care glucose testing devices.

Detecting and locating surrounding vehicles robustly and efficiently are essential capabilities for autonomous vehicles. Existing solutions often rely on vision-based methods or 3D LiDAR-based methods. These methods are either too expensive in both sensor pricing (3D LiDAR) and computation (camera and 3D LiDAR) or less robust in resisting harsh environment changes (camera). In this work, we revisit the LiDAR based approaches for vehicle detection with a less expensive 2D LiDAR by utilizing modern deep learning approaches. We aim at filling in the gap as few previous works conclude an efficient and robust vehicle detection solution in a deep learning way in 2D. To this end, we propose a learning based method with the input of pseudo-images, named Cascade Pyramid Region Proposal Convolution Neural Network (Cascade Pyramid RCNN), and a hybrid learning method with the input of sparse points, named Hybrid Resnet Lite. Experiments are conducted with our newly 2D LiDAR vehicle dataset recorded in complex traffic environments. Results demonstrate that the Cascade Pyramid RCNN outperforms state-of-the-art methods in accuracy while the proposed Hybrid Resnet Lite provides superior performance of the speed and lightweight model by hybridizing learning based and non-learning based modules. As few previous works conclude an efficient and robust vehicle detection solution with 2D LiDAR, our research fills in this gap and illustrates that even with limited sensing source from a 2D LiDAR, detecting obstacles like vehicles efficiently and robustly is still achievable.

Despite the reduction in the incidence of acute rejection, a major risk factor for graft loss, there has been only modest improvement in long-term graft survival. Most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or calcineurin inhibitor nephrotoxicity. Distinct immunologic and nonimmunologic factors conspire to lead to a common pathway of allograft fibrosis. It remains plausible that mitigating nonimmunologic damage using strategies proven effective in native kidney disease may yield benefit in kidney transplantation. In this review, we will focus on nonimmunologic aspects of kidney transplant care that may prove to be valuable adjuncts to a well-managed immunosuppression regimen. Topics to be addressed include the roles of hypertension and agents used to treat it, lipid lowering, sodium and water intake, elevated uric acid, metabolic acidosis, and the use of sodium-glucose cotransporter 2 inhibitors on long-term kidney transplant health.

Contains fulltext : 237261.pdf (Publisher’s version ) (Closed access) Adherence to national and international clinical practice guidelines is suboptimal throughout Europe. The European Association of Urology Guidelines Office project "IMAGINE" (IMpact Assessment of Guidelines Implementation and Education) has been developed to measure baseline adherence to urological guideline recommendations across Europe and to identify issues that drive nonadherence.

The latest WHO report estimates about 1.6 million global deaths annually from TB, which is further exacerbated by drug-resistant (DR) TB and comorbidities with diabetes and HIV. Exiguous dosing, incomplete treatment course, and the ability of the tuberculosis bacilli to tolerate and survive current first-line and second-line anti-TB drugs, in either their latent state or active state, has resulted in an increased prevalence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant TB (TDR-TB). Although a better understanding of the TB microanatomy, genome, transcriptome, proteome, and metabolome, has resulted in the discovery of a few novel promising anti-TB drug targets and diagnostic biomarkers of late, no new anti-TB drug candidates have been approved for routine therapy in over 50 years, with only bedaquiline, delamanid, and pretomanid recently receiving tentative regulatory approval. Considering this, alternative approaches for identifying possible new anti-TB drug candidates, for effectively eradicating both replicating and non-replicating Mycobacterium tuberculosis, are still urgently required. Subsequently, several antibiotic and non-antibiotic drugs with known treatment indications (TB targeted and non-TB targeted) are now being repurposed and/or derivatized as novel antibiotics for possible use in TB therapy. Insights gathered here reveal that more studies focused on drug-drug interactions between licensed and potential lead anti-TB drug candidates need to be prioritized. This write-up encapsulates the most recent findings regarding investigational compounds with promising anti-TB potential and drugs with repurposing potential in TB therapy.

Context Live surgery events (LSEs) have been used in all surgical fields for education and training and to demonstrate new techniques. The European Association of Urology (EAU) live surgery guidelines were established in 2014. Objective To review the compliance of outcomes for procedures performed at EAU-affiliated LSEs with the 2014 guidelines and to establish updated guidelines for LSEs and semi-LSEs. Evidence acquisition Patients from EAU-affiliated LSEs were included for all surgical procedures carried out between January 2015 and January 2020. All these events were pre-evaluated by the EAU Live Surgery Committee and met the criteria for an EAU LSE, with outcomes recorded and submitted to the registry. Data were collected for the type of procedure and for intraoperative and short- and long-term complications. Evidence synthesis A total of 246 procedures were performed across 18 LSEs, with an annual volume ranging from 19 to 74 procedures. These included 109 (44.3%) robot-assisted procedures, 21 (8.5%) laparoscopic procedures, 10 (4%) transurethral bladder procedures, 11 (4.4%) prostate enucleation procedures, 72 (29.2%) endourological procedures, and 23 (9.3%) andrology or reconstruction procedures. A total of 77 different surgical techniques and variations for 55 different types of surgery were performed as LSEs over the past 5 yr. There were 44 (17.8%) short-term complications and 11.3% (nine/79) long-term complications observed, with Clavien grade III/IV complications seen in 5.2% and 7.5% of cases over short- and long-term follow-up, respectively. Conclusions The 5-yr outcomes for EAU LSEs show that they are safe and follow previous guidelines set by the panel. It seems likely that the fine balance between patient safety and educational value might be best achieved if LSEs are performed by local surgeons in their parent hospital with patients and staff they know, and that technological advances will make live streaming a seamless process. The current EAU Live Surgery Committee has updated the guidelines on LSEs and provided new guidelines for semi-live events. Patient summary We reviewed 5-year outcomes for live surgery events endorsed by the European Association of Urology. We found that the operations carried out at these events were safe and followed the guidelines previously set. We have updated the guidelines and provided new guidelines for semi-live events.

Predicting the future trajectories of surrounding agents has become an crucial problem to be solved for the safety of autonomous vehicles. Recent studies based on Long Short Term Memory (LSTM) networks have shown powerful abilities to model social interactions. However, many of these approaches focus on spatial interactions of the neighborhood agents but ignore temporal interactions that accompany spatial interactions. In this paper, we propose a Hierarchical Spatio-Temporal Attention architecture (HSTA), which activates the utilization of spatial interactions with different weights, and jointly considers the temporal interactions across time steps of all agents. More specially, the graph attention mechanism (GAT) is presented to capture spatial interactions, the multi-head attention mechanism (MHA) is conducted to encode temporal correlations of interactions and a state gated fusion (SGF) layer is used to integrate spatial and temporal interactions. We evaluate our proposed method against baselines on both pedestrian and vehicle datasets. The results show that our model is effective and achieves state-of-the-art achievements.

BACKGROUND Pretransplant diabetes and new-onset diabetes after transplant (NODAT) are known risk factors for vascular events after kidney transplantation, but the incidence and magnitude of the risk of major adverse cardiovascular events (MACE) and cardiac deaths remain uncertain in recent era. METHODS A population cohort study of kidney transplant recipients identified using data from linked administrative healthcare databases from Ontario, Canada. The incidence rates of MACE (expressed as events with 95% confidence interval [95% CI] per 1000 person-years were reported according to diabetes status of pretransplant diabetes, NODAT, or no diabetes. Extended Cox regression model was used to examine the association between diabetes status, MACE, and cardiac death. RESULTS Of 5248 recipients, 1973 (38%) had pretransplant diabetes, and 799 (15%) developed NODAT with a median follow-up of 5.5 y. The incidence rates (95% CI) of MACE for recipients with pretransplant diabetes, NODAT, and no diabetes between 1 and 3 y posttransplant were 38.1 (32.1-45.3), 12.6 (6.3-25.2), and 11.8 (9.2-15.0) per 1000 person-years, respectively. Compared with recipients with pretransplant diabetes, recipients with NODAT experienced a lower risk of MACE (adjusted hazard ratio, 0.59; 95% CI, 0.47-0.74) but not cardiac death (adjusted hazard ratio, 0.97; 95% CI, 0.61-1.55). The rate of MACE and cardiac death was lowest in patients without diabetes. CONCLUSIONS Patients with pretransplant diabetes incur the greatest rate of MACE and cardiac deaths after transplantation. Having NODAT also bears high burden of vascular events compared with those without diabetes, but the magnitude of the increased rate remains lower than recipients with pretransplant diabetes.

Patients with non-small cell lung cancer (NSCLC) harboring ROS proto-oncogene 1 (ROS1) gene rearrangements show dramatic response to the tyrosine kinase inhibitor (TKI) crizotinib. Current best practice guidelines recommend that all advanced stage non-squamous NSCLC patients be also tested for ROS1 gene rearrangements. Several studies have suggested that ROS1 immunohistochemistry (IHC) using the D4D6 antibody may be used to screen for ROS1 fusion positive lung cancers, with assays showing high sensitivity but moderate to high specificity. A break apart fluorescence in situ hybridization (FISH) test is then used to confirm the presence of ROS1 gene rearrangement. The goal of Canadian ROS1 (CROS) study was to harmonize ROS1 laboratory developed testing (LDT) by using IHC and FISH assays to detect ROS1 rearranged lung cancers across Canadian pathology laboratories. Cell lines expressing different levels of ROS1 (high, low, none) were used to calibrate IHC protocols after which participating laboratories ran the calibrated protocols on a reference set of 24 NSCLC cases (9 ROS1 rearranged tumors and 15 ROS1 non-rearranged tumors as determined by FISH). Results were compared using a centralized readout. The stained slides were evaluated for the cellular localization of staining, intensity of staining, the presence of staining in non-tumor cells, the presence of non-specific staining (e.g. necrosis, extracellular mater, other) and the percent positive cells. H-score was also determined for each tumor. Analytical sensitivity and specificity harmonization was achieved by using low limit of detection (LOD) as either any positivity in the U118 cell line or H-score of 200 with the HCC78 cell line. An overall diagnostic sensitivity and specificity of up to 100% and 99% respectively was achieved for ROS1 IHC testing (relative to FISH) using an adjusted H-score readout on the reference cases. This study confirms that LDT ROS1 IHC assays can be highly sensitive and specific for detection of ROS1 rearrangements in NSCLC. As NSCLC can demonstrate ROS1 IHC positivity in FISH-negative cases, the degree of the specificity of the IHC assay, especially in highly sensitive protocols, is mostly dependent on the readout cut-off threshold. As ROS1 IHC is a screening assay for a rare rearrangements in NSCLC, we recommend adjustment of the readout threshold in order to balance specificity, rather than decreasing the overall analytical and diagnostic sensitivity of the protocols.

Temperature sensitive electrical parameters (TSEPs) are used to determine the chip temperature of a single-chip insulated gate bipolar transistors (IGBT) power module by measuring one electrical device parameter. Commonly, most TSEPs have a linear relationship between the chip temperature and the electrical parameter. Like any sensor, preferred attributes of TSEPs include good accuracy, linearity, and sensitivity. For multichip IGBTs (mIGBTs) modules, these can only be achieved when all chips have the same temperature. Equal chip temperatures among different semiconductor chips can be achieved when placing mIGBTs in environmental chambers to produce a homogeneous temperature distribution (HTD). In real applications, however, mIGBTs are power cycled and are exposed to inhomogeneous temperature distribution (ITD) where temperature differences exist between chips. Consequently, measuring one electric parameter only cannot represent each chip temperature which impacts the TSEP sensitivity, linearity, and accuracy. This article compares the performance of ten TSEPs applied to an mIGBT module operating at HTD and ITD conditions in order to determine which TSEPs are most suitable for mIGBTs in real applications.

Purpose The aim of the present study was to assess the impact of postponed screening examinations and lockdown measures on gynecological and breast cancer diagnoses throughout the year 2020 in a gynecological oncological center in Austria. Methods Data of 889 patients with either newly diagnosed gynecological or breast cancer between January 2019 and December 2020 were collected. Clinical parameters including symptoms, performance status, comorbidities and referral status were compared in patients, who were newly diagnosed with cancer in the period of the first lockdown from March 2020 to April 2020 and the second lockdown from November 2020 to December 2020 and compared to the same period in 2019. Results Our results showed a strong decline in newly diagnosed cancers during the lockdown periods: −45% in gynecological cancer and -52% in breast cancer compared to the same period in 2019. Compared to the analogue period of 2019, breast cancer patients reported significantly more tumor-associated symptoms (55% vs. 31%, p = 0.013) during and in between (48% vs. 32%, p = 0.022) the lockdowns. During the lockdown, periods in the group of breast cancer patients’ tumor stage varied significantly compared to 2019 (T2–T4; p = 0.047). Conclusion Both lockdowns led to a strong decrease in newly diagnosed gynecological and breast cancers. Treatment delays in potentially curable disease could lead to inferior clinical outcomes, with the risk of missing the optimal treatment window. As the COVID-19 pandemic will be a challenge for some time to come, new strategies in patient care are needed to optimize cancer screening and management during the pandemic.

Advanced deep learning technology has made great progress in generic object detection of autonomous driving, yet it is still challenging to detect small road hazards in a long distance owing to lack of large-scale small-object datasets and dedicated methods. This work addresses the challenge from two aspects. Firstly, a self-collected long-distance road object dataset (TJ-LDRO) is introduced, which consists of 109,337 images and is the largest dataset so far for the small road object detection research. Secondly, a vanishing-point-guided context-aware network (VCANet) is proposed, which utilizes the vanishing point prediction block and the context-aware center detection block to obtain semantic information. The multi-scale feature fusion pipeline and the upsampling block in VCANet are introduced to enhance the region of interest (ROI) feature. The experimental results with TJ-LDRO dataset show that the proposed method achieves better performance than the representative generic object detection methods. This work fills a critical capability gap in small road hazards detection for high-speed autonomous vehicles.

This work presents I-DVFS: a novel approach to perform instantaneously the frequency switch during dynamic voltage frequency scaling (DVFS). The I-DVFS, unlike legacy DVFS, does not require halting an IPs execution to perform a DVFS transition, and thus, the performance overhead of DVFS is both reduced and more deterministic. Such attributes enable the more frequent use of DVFS and, thus, improve an IPs performance, power, and energy efficiency. Nonetheless, the overlapping of an IPs DVFS transition with the normal IPs execution creates a number of issues that need careful treatment at design time to ensure the reliable operation in the field. This article presents these issues and elucidates on how they are addressed in an implementation of I-DVFS that has been productized and can be found in millions of CPUs.

Summary Background The Gambia introduced seven-valent pneumococcal conjugate vaccine (PCV7) in August 2009, followed by PCV13 in May, 2011, using a schedule of three primary doses without a booster dose or catch-up immunisation. We aimed to assess the long-term impact of PCV on disease incidence. Methods We did 10 years of population-based surveillance for invasive pneumococcal disease (IPD) and WHO defined radiological pneumonia with consolidation in rural Gambia. The surveillance population included all Basse Health and Demographic Surveillance System residents aged 2 months or older. Nurses screened all outpatients and inpatients at all health facilities using standardised criteria for referral. Clinicians then applied criteria for patient investigation. We defined IPD as a compatible illness with isolation of Streptococcus pneumoniae from a normally sterile site (cerebrospinal fluid, blood, or pleural fluid). We compared disease incidence between baseline (May 12, 2008–May 11, 2010) and post-vaccine years (2016–2017), in children aged 2 months to 14 years, adjusting for changes in case ascertainment over time. Findings We identified 22 728 patients for investigation and detected 342 cases of IPD and 2623 cases of radiological pneumonia. Among children aged 2–59 months, IPD incidence declined from 184 cases per 100 000 person-years to 38 cases per 100 000 person-years, an 80% reduction (95% CI 69–87). Non-pneumococcal bacteraemia incidence did not change significantly over time (incidence rate ratio 0·88; 95% CI, 0·64–1·21). We detected zero cases of vaccine-type IPD in the 2–11 month age group in 2016–17. Incidence of radiological pneumonia decreased by 33% (95% CI 24–40), from 10·5 to 7·0 per 1000 person-years in the 2–59 month age group, while pneumonia hospitalisations declined by 27% (95% CI 22–31). In the 5–14 year age group, IPD incidence declined by 69% (95% CI −28 to 91) and radiological pneumonia by 27% (95% CI −5 to 49). Interpretation Routine introduction of PCV13 substantially reduced the incidence of childhood IPD and pneumonia in rural Gambia, including elimination of vaccine-type IPD in infants. Other low-income countries can expect substantial impact from the introduction of PCV13 using a schedule of three primary doses. Funding Gavi, The Vaccine Alliance; Bill & Melinda Gates Foundation; UK Medical Research Council; Pfizer Ltd.

BACKGROUND: Pneumonia remains the leading infectious cause of death among children

Background Effective hand washing (for at least 20 s, with water and soap) is one of the health behaviors protecting against infection transmissions. Behavior change interventions supporting the initiation and maintenance of hand washing are crucial to prevent infection transmissions. Based on the Health Action Process Approach, the aim of this research was to conduct a pre-post analysis of hand washing and related cognitions (i.e., intention, self-efficacy, self-monitoring), measured up to 100 days following an intervention. Methods A convenience sample of N = 123 participants (age: M = 23.96 years; SD = 5.82; 80% women) received a brief intervention (key behavior change techniques: information about health consequences of hand washing; action planning) and responded to daily diaries and questionnaires up to a 100-day follow-up. Two-level models were used to analyze data of n = 89 participants who provided longitudinal data. Results Hand washing and self-monitoring increased, whereas intention and self-efficacy decreased over time. Only self-monitoring was a consistent positive correlate of hand washing on a between-person level. Conclusions Hand washing and self-monitoring considerably increased over several weeks following the intervention. Future research testing the intervention against a control condition is needed to rule out that changes in behavior and cognitions might have been prompted by completing the daily diaries. Trial Registration German Clinical Trials Register; https://www.drks.de; registration number: DRKS00022067.

BACKGROUND Despite recent declines in new pediatric HIV infections and childhood HIV-related deaths, pneumonia remains the leading cause of death in HIV-infected children under 5. We describe the patient population, etiology and outcomes of childhood pneumonia in Zambian HIV-infected children. METHODS As one of the 9 sites for the Pneumonia Etiology Research for Child Health study, we enrolled children 1-59 months of age presenting to University Teaching Hospital in Lusaka, Zambia, with World Health Organization-defined severe and very severe pneumonia. Controls frequency-matched on age group and HIV infection status were enrolled from the Lusaka Pediatric HIV Clinics as well as from the surrounding communities. Clinical assessments, chest radiographs (CXR; cases) and microbiologic samples (nasopharyngeal/oropharyngeal swabs, blood, urine, induced sputum) were obtained under highly standardized procedures. Etiology was estimated using Bayesian methods and accounted for imperfect sensitivity and specificity of measurements. RESULTS Of the 617 cases and 686 controls enrolled in Zambia over a 24-month period, 103 cases (16.7%) and 85 controls (12.4%) were HIV infected and included in this analysis. Among the HIV-infected cases, 75% were

Background HIV-1 infection predisposes to an increased burden of pneumonia caused by community-acquired and opportunistic pathogens. Methods Within the context of the Pneumonia Etiology Research for Child Health case-control study of under 5 pneumonia, we investigated the etiology of World Health Organization-defined severe/very severe pneumonia requiring hospitalization in South African HIV-infected children. Nasopharyngeal-oropharyngeal swabs and blood, collected from cases and age- and season-matched HIV-infected controls attending outpatient antiretroviral therapy (ART) clinics, were analyzed using molecular diagnostic methods. Cases were also investigated for tuberculosis. Etiologic fractions among cases with radiologically confirmed pneumonia were derived using Bayesian analytic techniques. Results Of 115 HIV-infected cases, 89 (77.4%) had radiologically confirmed pneumonia. Severe immunosuppression (adjusted odds ratio, 32.60; 95% confidence interval, 7.25-146.64) was significantly associated with radiologically confirmed pneumonia. Cotrimoxazole prophylaxis (46.4% vs. 77.4%) and ART (28.2% vs. 83.1%) coverage were significantly lower in cases compared with ART-clinic controls. An etiologic agent was identified in 99.0% of the radiologically confirmed cases. The 'top 4' pathogens associated with radiologically confirmed pneumonia were Pneumocystis jirovecii [23.0%; 95% credible interval (CrI), 12.4%-31.5%], Staphylococcus aureus (10.6%; 95% CrI, 2.2%-20.2%), pneumococcus (9.5%; 95% CrI, 2.2%-18.0%) and respiratory syncytial virus (9.3%; 95% CrI, 2.2%-14.6%). Bacteremia (6.7%) and in-hospital death (10.1%) were frequent among those with radiologically confirmed disease. Conclusions Pneumocystis jirovecii, S. aureus, pneumococcus and respiratory syncytial virus contribute a considerable burden of radiologically confirmed pneumonia in South African HIV-infected children under 5 years. Expediting access to ART and cotrimoxazole prophylaxis would decrease the burden of pneumonia in these children.

Supplemental Digital Content is available in the text., Background: Pneumonia remains the leading cause of death in young children globally. The changing epidemiology of pneumonia requires up-to-date data to guide both case management and prevention programs. The Gambia study site contributed a high child mortality, high pneumonia incidence, low HIV prevalence, Haemophilus influenzae type b and pneumococcal conjugate vaccines-vaccinated rural West African setting to the Pneumonia Etiology Research for Child Health (PERCH) Study. Methods: The PERCH study was a 7-country case-control study of the etiology of hospitalized severe pneumonia in children 1–59 months of age in low and middle-income countries. Culture and nucleic acid detection methods were used to test nasopharyngeal/oropharyngeal swabs, blood, induced sputum and, in selected cases, lung or pleural fluid aspirates. Etiology was determined by integrating case and control data from multiple specimens using the PERCH integrated analysis based on Bayesian probabilistic methods. Results: At The Gambia study site, 638 cases of World Health Organization-defined severe and very severe pneumonia (286 of which were chest radiograph [CXR]-positive and HIV-negative) and 654 age-frequency matched controls were enrolled. Viral causes predominated overall (viral 58% vs. bacterial 28%), and of CXR-positive cases respiratory syncytial virus (RSV) accounted for 37%, Streptococcus pneumoniae 13% and parainfluenza was responsible for 9%. Nevertheless, among very severe cases bacterial causes dominated (77% bacterial vs. 11% viral), led by S. pneumoniae (41%); Mycobacterium tuberculosis, not included in “bacterial”, accounted for 9%. 93% and 80% of controls ≥1 year of age were, respectively, fully vaccinated for age against Haemophilus influenzae and S. pneumoniae. Conclusions: Viral causes, notably RSV, predominated in The Gambia overall, but bacterial causes dominated the severest cases. Efforts must continue to prevent disease by optimizing access to existing vaccines, and to develop new vaccines, notably against RSV. A continued emphasis on appropriate case management of severe pneumonia remains important.

Background Pneumonia is the major contributor to under 5 childhood mortality globally. We evaluated the etiology of pneumonia amongst HIV-uninfected South African children enrolled into the Pneumonia Etiology Research for Child Health case-control study. Methods Cases, 1-59 months of age hospitalized with World Health Organization clinically defined severe/very severe pneumonia, were frequency-matched by age and season to community controls. Nasopharyngeal-oropharyngeal swabs were analyzed using polymerase chain reaction for 33 respiratory pathogens, and whole blood was tested for pneumococcal autolysin. Cases were also tested for Mycobacterium tuberculosis. Population etiologic fractions (EF) of pneumonia with radiologic evidence of consolidation/infiltrate were derived for each pathogen through Bayesian analysis. Results Of the 805 HIV-uninfected cases enrolled based on clinical criteria, radiologically confirmed pneumonia was evident in 165 HIV-exposed, -uninfected, and 246 HIV-unexposed children. In HIV-exposed and HIV-unexposed children, respiratory syncytial virus was the most important pathogen with EFs of 31.6% [95% credible interval (CrI), 24.8%-38.8%] and 36.4% (95% CrI, 30.5%-43.1%), respectively. M. tuberculosis contributed EFs of 11.6% (95% CrI, 6.1%-18.8%) in HIV-exposed and 8.3% (95% CrI, 4.5%-13.8%) in HIV-unexposed children, including an EF of 16.3% (95% CrI, 6.1%-33.3%) in HIV-exposed children ≥12 months of age. Bacteremia (3.0% vs. 1.6%) and case fatality risk (3.6% vs. 3.7%) were similar in HIV-exposed and HIV-unexposed children. Conclusions Vaccination strategies targeting respiratory syncytial virus should be prioritized for prevention of pneumonia in children. Furthermore, interventions are required to address the high burden of tuberculosis in the pathogenesis of acute community-acquired pneumonia in settings such as ours.

Background Childhood pneumonia in developing countries is the foremost cause of morbidity and death. Fresh information on etiology is needed, considering the changing epidemiology of pneumonia in the setting of greater availability of effective vaccines, changing antibiotic use and improved access to care. We report here the Zambia site results of the Pneumonia Etiology Research for Child Health study on the etiology of pneumonia among HIV-uninfected children in Lusaka, Zambia. Methods We conducted a case-control study of HIV-uninfected children age 1-59 months admitted with World Health Organization-defined severe or very severe pneumonia to a large tertiary care hospital in Lusaka. History, physical examination, chest radiographs (CXRs), blood cultures and nasopharyngeal/oropharyngeal swabs were obtained and tested by polymerase chain reaction and routine microbiology for the presence of 30 bacteria and viruses. From age and seasonally matched controls, we tested blood and nasopharyngeal/oropharyngeal samples. We used the Pneumonia Etiology Research for Child Health integrated analysis to determine the individual and population etiologic fraction for individual pathogens as the cause of pneumonia. Results Among the 514 HIV-uninfected case children, 208 (40.5%) had abnormal CXRs (61 of 514 children were missing CXR), 8 (3.8%) of which had positive blood cultures. The overall mortality was 16.0% (82 deaths). The etiologic fraction was highest for respiratory syncytial virus [26.1%, 95% credible interval (CrI): 17.0-37.7], Mycobacterium tuberculosis (12.8%, 95% CrI: 4.3-25.3) and human metapneumovirus (12.8%, CrI: 6.1-21.8). Conclusions Childhood pneumonia in Zambia among HIV-uninfected children is most frequently caused by respiratory syncytial virus, M. tuberculosis and human metapneumovirus, and the mortality remains high.

Background: In the 1980s, Streptococcus pneumoniae and Haemophilus influenzae were identified as the principal causes of severe pneumonia in children. We investigated the etiology of severe childhood pneumonia in Kenya after introduction of conjugate vaccines against H. influenzae type b, in 2001, and S. pneumoniae, in 2011. Methods: We conducted a case–control study between August 2011 and November 2013 among residents of the Kilifi Health and Demographic Surveillance System 28 days to 59 months of age. Cases were hospitalized at Kilifi County Hospital with severe or very severe pneumonia according to the 2005 World Health Organization definition. Controls were randomly selected from the community and frequency matched to cases on age and season. We tested nasal and oropharyngeal samples, sputum, pleural fluid, and blood specimens and used the Pneumonia Etiology Research for Child Health Integrated Analysis, combining latent class analysis and Bayesian methods, to attribute etiology. Results: We enrolled 630 and 863 HIV-uninfected cases and controls, respectively. Among the cases, 282 (44%) had abnormal chest radiographs (CXR positive), 33 (5%) died in hospital, and 177 (28%) had diagnoses other than pneumonia at discharge. Among CXR-positive pneumonia cases, viruses and bacteria accounted for 77% (95% CrI: 67%–85%) and 16% (95% CrI: 10%–26%) of pneumonia attribution, respectively. Respiratory syncytial virus, S. pneumoniae and H. influenza, accounted for 37% (95% CrI: 31%–44%), 5% (95% CrI: 3%–9%), and 6% (95% CrI: 2%–11%), respectively. Conclusions: Respiratory syncytial virus was the main cause of CXR-positive pneumonia. The small contribution of H. influenzae type b and pneumococcus to pneumonia may reflect the impact of vaccine introductions in this population.

BackgroundGlobally,Haemophilus influenzaetype b (Hib) vaccine has substantially reduced the burden of Hib invasive disease. However, China remains the only country not to include Hib vaccine into its national immunization program (NIP), although it accounts for 11% of global Hib deaths. We aimed to assess the cost-effectiveness of including Hib vaccine in China’s NIP at the national and provincial levels.MethodsUsing a decision-tree Markov state transition model, we estimated the cost-effectiveness of Hib vaccine in the NIP compared to thestatus quoof Hib vaccine in the private market for the 2017 birth cohort. Treatment costs and vaccine program costs were calculated from Chinese Center for Disease Control and Prevention (CDC) and national insurance databases. Epidemiological data and other model parameters were obtained from published literature. Cases and deaths averted, quality-adjusted life years (QALYs) gained, and incremental cost-effectiveness ratios (ICER) were predicted by province. Deterministic and probabilistic sensitivity analyses were performed to explore model uncertainty.ResultsIncluding Hib vaccine in the NIP was projected to prevent approximately 2700 deaths (93% reduction) and 235,700 cases of Hib disease (92% reduction) for the 2017 birth cohort at the national level. Hib vaccine was cost-effective nationally (US$ 8001 per QALY gained) compared to the GDP per capita and cost-effective in 15 of 31 provinces. One-way and scenario sensitivity analyses indicated results were robust when varying model parameters, and in probabilistic sensitivity analysis, Hib vaccine had a 64% probability of being cost-effective nationally.ConclusionIntroducing Hib vaccine in China’s NIP is cost-effective nationally and in many provinces. Less socioeconomically developed provinces with high Hib disease burden and low access to Hib vaccine in the current private market, such as those in the west region, would benefit the most from adding Hib vaccine to the NIP. In the absence of a national policy decision on Hib vaccine, this analysis provides evidence for provincial governments to include Hib vaccine into local immunization programs to substantially reduce disease burden and treatment costs.

In 2016 a collection of guiding principles for the management of scientific data was proposed by a consortium of scientists and organizations under the acronym FAIR (Findability, Accessibility, Interoperability, Reusability). As many other disciplines, control theory also is affected by the (mostly unintended) disregard of these principles and to some degree also suffers from a reproducibility crisis. The specific situation for that discipline, however, is more related to software, than to classical numerical data. In particular, since computational methods like simulation, numeric approximation or computer algebra play an important role, the reproducibility of results relies on implementation details, which are typically out of scope for written papers.While some publications do reference the source code of the respective software, this is by far not standard in industry and academia. Additionally, having access to the source code does not imply reproducibility due to dependency issues w. r. t. hardware and software components. This paper proposes a tool based approach consisting of four components to mitigate the problem: a) an open repository with a suitable data structure to publish formal problem specifications and problem solutions (each represented as source code) along with descriptive metadata, b) a web service that automatically checks the solution methods against the problem specifications and auxiliary software for local testing, c) a computational ontology which allows for semantic tagging and sophisticated querying the entities in the repo and d) a peer-oriented process scheme to organize both the contribution process to that repository and formal quality assurance.

This paper aims to encourage a debate on the proposed transactive relationship between voice and contemporary social, economic and technological (SET) developments. Specifically, we propose that SET developments change how work is approached, organized and designed, and that these changes challenge employee rights, roles and responsibilities. How employees deal with these challenges affects their well-being and health, and whether organizations and societies can develop sustainably. While voice is a way for employees to have a say in these developments, we argue that SET changes can be times at which voice is threatened. Moreover, we propose that SET changes urge us to question and reshape our understanding of voice. We propose that a functional conceptualization of voice provides opportunities to integrate existing approaches which are often scattered across disciplines, and is inclusive of new opportunities and constraints that come with SET developments. Using examples of two meta-trends, we illustrate how SET changes challenge traditional conceptualizations of voice and identify ‘new trajectories’ to expand more inclusive forms of voice and more useful research paradigms. These meta-trends are digitalization (including new business models and employment forms, alternative/flexible work arrangements, technology-mediated communication) and diversification (including internationalization and marginalized/minority groups).

With the process of urbanization, the problem of insufficient parking spaces has become prominent. Adopting a high-density parking lot with parking robots can greatly improve the land utilization rate of the parking lot. This article tackles the multiple parking robots scheduling problem of high-density layout parking lots, including task execution sequence decision, robot allocation, and cooperative path planning. First, we mathematically describe the parking robot scheduling problem. Existing approximation algorithms are often far from the optimal solution. This article proposes an improved genetic algorithm and a time-enhanced A* path planning algorithm for high-density parking lots. The improved genetic algorithm can efficiently search task execution sequence and robot allocation and converge to the optimal solution even in large-scale complex scenarios. Meanwhile, the time-enhanced A* algorithm takes a new dimension “the time” into consideration, together with the distance, and security factors, to solve the multi-parking-robot path planning problem. Simulation experiments show that our algorithm can improve scheduling performance in many aspects such as task execution time, driving distance, and security in large-scale high-density parking lots. This article provides an efficient and convenient scheduling solution for the implementation of the high-density unmanned parking lot.

Background More and more information about complementary and integrative medicine is becoming available, especially among cancer patients. However, little is known about the use of herbal medicine by patients with gynecologic cancers. This study aimed to assess the use of herbal products by gynecologic cancer patients compared with healthy controls. Methods This cross-sectional study was conducted at the Department for Gynecology and Obstetrics of Erlangen University Hospital and included 201 patients with gynecologic cancer and 212 healthy controls. Use of herbal medicines was evaluated using a standardized questionnaire. Medical information on cancer patients was collected from hospital records. Group comparisons were done using a logistic regression model. Risk ratios were assessed using a Poisson regression model. Results Gynecologic cancer patients used herbal medicine significantly less often than healthy persons. 69% of gynecologic cancer patients and 81% of healthy participants reported using herbal products. 40% of cancer patients and 56% of healthy persons reported using plants for medicinal purposes. Motives of cancer patients for using herbal medicine included treatment of cancer-related symptoms. The major source of information for both groups was family and friends. Conclusions Although herbal medicine was used less by patients with gynecologic cancer, herbal products were used by both cancer patients and healthy individuals. To provide cancer patients with optimal therapy, oncologists should be informed about the herbal products used by their patients as this will allow them to take their patientsʼ self-medication with herbal medicine into account. Counseling by oncologists on the use of herbal medicine should be encouraged.

PurposeThis article investigates which criteria and processes are used to identify global leadership potential (GLP) in multinational corporations.Design/methodology/approachFirst, the literature at the intersection between leadership potential and global leadership is reviewed to identify a set of criteria that can be used for assessing GLP. The findings are then validated in a qualitative study against a sample of nine global corporations.FindingsSeveral traits (integrity and resilience), attitudes (learning orientation, motivation to lead, change orientation, drive for results, customer orientation and a global mindset) and competencies (cognitive complexity and intercultural, interpersonal, leadership, learning, change and business competencies) are associated with GLP. The core steps in the GLP identification process are nomination, assessment and confirmation. These steps can be complemented by a preassessment phase and a subsequent talent dialogue.Practical implicationsThe results of this research can inform human resource (HR) management practitioners in their endeavor to successfully identify and assess potential future global leaders.Originality/valuePrior research has focused either on defining global leadership or on assessing leadership potential in general, without a clear focus on identifying global leaders. In this article, the two concepts of global leadership and leadership potential are combined, thus providing an integrated content and process model that indicates how global corporations select their future global leaders.

The growing opioid crisis increasingly affects maternal care in the US and it is unknown if opioid use puts pregnant women at increased odds for cesarean delivery (CD). Understanding how opioids influence CD trends is important in improving maternal and neonatal outcomes. This study aims to understand the association of opioid use with CD in the context of the demographic, clinical, behavioral, and health system complexity. This retrospective cross-sectional analysis used representative data from the 2012–2014 National Inpatient Sample. Opioid use during pregnancy, CD, and other clinical variables were identified using ICD9 codes. Characteristics were assessed using bivariate and multivariate statistics. A logistic regression model was used to determine the association between opioid use and CD while controlling for confounders. Adjustments were made for rural/urban hospital location, regional median income, maternal age, race, and medical and pregnancy-related conditions. The rate of CD in the overall sample was about 30%. Among opioids-users, the overall proportion of CD was significantly less (24.7%). The adjusted odds ratio for CD among opioids users was 0.74 (CI: 0.73–0.76, p

Background Immune cells play a major role in the pathogenesis of COPD. Changes in the distribution and cellular functions of major immune cells, such as alveolar macrophages (AMs) and neutrophils are well known; however, their transcriptional reprogramming and contribution to the pathophysiology of COPD are still not fully understood. Method To determine changes in transcriptional reprogramming and lipid metabolism in the major immune cell type within bronchoalveolar lavage fluid, we analysed whole transcriptomes and lipidomes of sorted CD45+Lin−HLA-DR+CD66b−Autofluorescencehi AMs from controls and COPD patients. Results We observed global transcriptional reprogramming featuring a spectrum of activation states, including pro- and anti-inflammatory signatures. We further detected significant changes between COPD patients and controls in genes involved in lipid metabolism, such as fatty acid biosynthesis in GOLD2 patients. Based on these findings, assessment of a total of 202 lipid species in sorted AMs revealed changes of cholesteryl esters, monoacylglycerols and phospholipids in a disease grade-dependent manner. Conclusions Transcriptome and lipidome profiling of COPD AMs revealed GOLD grade-dependent changes, such as in cholesterol metabolism and interferon-α and γ responses., AMs from COPD patients undergo GOLD grade-specific transcriptional reprogramming and acquire a complex activation profile. Among the observed changes are gene programmes involved in lipid metabolism that translate into alterations in the AM lipidome. https://bit.ly/3sYAqgd

Interconception care (ICC) is recommended to reduce maternal risk factors for poor birth outcomes between pregnancies. The IMPLICIT ICC model includes screening and brief intervention for mothers at well child visits (WCVs) for smoking, depression, multivitamin use, and family planning. Prior studies demonstrate feasibility and acceptability among providers and mothers, but not whether mothers recall receipt of targeted messages. Mothers accompanying their child at 12- and 24-month WCVs at four sites of a family medicine academic practice were surveyed pre (2012) and post (2018) ICC model implementation. Survey items assessed health history, behaviors, and report of whether their child’s physician addressed maternal depression, tobacco use, family planning, and folic acid supplementation during WCVs. Pre and post results are compared using logistic regression adjusting for demographics and insurance. Our sample included 307 distinct mothers with 108 and 199 respondents in the pre and post periods, respectively. Mothers were more likely to report discussions with their child’s doctor post-intervention for family planning (31% pre to 86% post; aOR 18.65), depression screening (63–85%; aOR 5.22), and taking a folic acid supplement (53–68%; aOR 2.54). Among mothers who smoked, the percentage that reported their child’s doctor recommended cessation increased from 56 to 75% (aOR = 3.66). The IMPLICIT ICC model resulted in increased reported health care provider discussions of four key areas of interconception health by mothers attending WCVs. This model holds promise as a primary care strategy to systematically address maternal risks associated with poor pregnancy outcomes.

Spiking neural networks (SNN) are among the most computationally intensive types of simulation models, with node counts on the order of up to 10 11 . Currently, there is intensive research into hardware platforms suitable to support large-scale SNN simulations, whereas several of the most widely used simulators still rely purely on the execution on CPUs. Enabling the execution of these established simulators on heterogeneous hardware allows new studies to exploit the many-core hardware prevalent in modern supercomputing environments, while still being able to reproduce and compare with results from a vast body of existing literature. In this article, we propose a transition approach for CPU-based SNN simulators to enable the execution on heterogeneous hardware (e.g., CPUs, GPUs, and FPGAs), with only limited modifications to an existing simulator code base and without changes to model code. Our approach relies on manual porting of a small number of core simulator functionalities as found in common SNN simulators, whereas the unmodified model code is analyzed and transformed automatically. We apply our approach to the well-known simulator NEST and make a version executable on heterogeneous hardware available to the community. Our measurements show that at full utilization, a single GPU achieves the performance of about 9 CPU cores. A CPU-GPU co-execution with load balancing is also demonstrated, which shows better performance compared to CPU-only or GPU-only execution. Finally, an analytical performance model is proposed to heuristically determine the optimal parameters to execute the heterogeneous NEST.

To perform an otopathologic analysis of temporal bones (TBs) with CHARGE syndrome.Otopathologic study of human TB specimens.Otopathology laboratories.From the otopathology laboratories at the University of Minnesota and Massachusetts Eye and Ear Infirmary, we selected TBs from donors with CHARGE syndrome. These TBs were serially sectioned at a thickness of 20 µm, and every 10th section was stained with hematoxylin and eosin. We performed otopathologic analyses of the external ear, middle ear (middle ear cleft, mucosal lining, ossicles, mastoid, and facial nerve), and inner ear (cochlea, vestibule, internal auditory canal, and cochlear and vestibular nerves). The gathered data were statistically analyzed.Our study included 12 TBs from 6 donors. We found a high prevalence of abnormalities affecting the ears. The most frequent findings were stapes malformation (100%), aberrant course of the facial nerve (100%) with narrow facial recess (50%), sclerotic and hypodeveloped mastoids (50%), cochlear (100%) and vestibular (83.3%) hypoplasia with aplasia of the semicircular canals, hypoplasia and aplasia of the cochlear (66.6%) and vestibular (91.6%) nerves, and narrowing of the bony canal of the cochlear nerve (66.6%). The number of spiral ganglion and Scarpa's ganglion neurons were decreased in all specimens (versus normative data).In our study, CHARGE syndrome was associated with multiple TB abnormalities that may severely affect audiovestibular function and rehabilitation.

Urinary inulin clearance is considered the gold standard of glomerular filtration rate (GFR) measurement but plasma clearance of less expensive and more accessible tracers is more commonly performed. Many plasma sampling protocols exist but little is known about their accuracy. Here, the study objectives were to compare plasma iohexol and 99mTc-DTPA GFR with varying sampling strategies to the GFR measured by urinary inulin and to identify protocols with the greatest accuracy according to clinical characteristics. GFR was measured simultaneously using urinary inulin, plasma iohexol, and plasma 99mTc DTPA clearance. Blood was sampled from 2 to 10 hours after injection. For each method, bias, precision, and accuracy (P30 and mean absolute error) were calculated for the entire cohort and for eGFR-EPI creatinine subgroups (

The hand gesture recognition system is a noncontact and intuitive communication approach, which, in turn, allows for natural and efficient interaction. This work focuses on developing a novel and robust gesture recognition system, which is insensitive to environmental illumination and background variation. In the field of gesture recognition, standard vision sensors, such as CMOS cameras, are widely used as the sensing devices in state-of-the-art hand gesture recognition systems. However, such cameras depend on environmental constraints, such as lighting variability and the cluttered background, which significantly deteriorates their performances. In this work, we propose an event-based gesture recognition system to overcome the detriment constraints and enhance the robustness of the recognition performance. Our system relies on a biologically inspired neuromorphic vision sensor that has microsecond temporal resolution, high dynamic range, and low latency. The sensor output is a sequence of asynchronous events instead of discrete frames. To interpret the visual data, we utilize a wearable glove as an interaction device with five high-frequency (>100 Hz) active LED markers (ALMs), representing fingers and palm, which are tracked precisely in the temporal domain using a restricted spatiotemporal particle filter algorithm. The latency of the sensing pipeline is negligible compared with the dynamics of the environment as the sensor’s temporal resolution allows us to distinguish high frequencies precisely. We design an encoding process to extract features and adopt a lightweight network to classify the hand gestures. The recognition accuracy of our system is comparable to the state-of-the-art methods. To study the robustness of the system, experiments considering illumination and background variations are performed, and the results show that our system is more robust than the state-of-the-art deep learning-based gesture recognition systems. Note to Practitioners —This article addresses the robustness of the hand gesture recognition system that is important for gesture recognition-based applications. Existing methods rely on either the large-volume data to train a deep learning model or to restrict the applied environments (e.g., an ideal environment without dynamic background). However, a vision-based deep learning model requires large computational resources, while the ideal environment limits the practicality of the system. In this work, we introduce a biologically inspired neuromorphic vision sensor and an ALM glove and build a novel gesture recognition system to tackle the above issue. The neuromorphic vision sensor has a microsecond temporal resolution and a high dynamic range. With these properties, the sensing system of our prototype operates in a very low-latency space, which, in turn, ensures that our gesture recognition system is robust to illumination variance and dynamic background. Thus, this work is valuable to the research of illumination-robust gesture recognition systems. Preliminary experiments suggest that our system prototype is feasible, but it has not yet been incorporated into an online gesture recognition system nor tested with complex gestures. In future work, we will concentrate on the improvement of the signal processing methods that advance the current system to complex and practical applications.

Background The impact of post-transplant red blood cell transfusion (RBCT) and their potential immunomodulatory effects on kidney transplant recipients are unclear. We examined the risks for adverse graft outcomes associated with post-kidney transplant RBCT. Methods We conducted a retrospective cohort study of all adult kidney transplant recipients at The Ottawa Hospital from 2002 to 2018. The exposure of interest was receipt of a RBCT after transplant categorized as 1, 2, 3-5 and >5 RBC. Outcomes of interest were rejection and death-censored graft loss (DCGL). Cox proportional hazards models were used to calculate hazard ratios (HR) with RBCT as a time-varying, cumulative exposure. Results Among 1,258 kidney transplant recipients, 468 (37.2%) received 2,373 a total of RBCT, 197 (15.7%) had rejection and 114 (9.1%) DCGL. For the receipt of 1, 2, 3-5 and >5 RBCT, compared to individuals never transfused, the adjusted HRs (95% CI) for rejection were 2.47 (1.62 to 3.77), 1.27 (0.77 to 2.11), 1.74 (1.00 to 3.05) and 2.23 (1.13 to 4.40) respectively; DCGL 2.32 (1.02 to 5.27), 3.03 (1.62 to 5.64), 7.50 (4.19 to 13.43) and 14.63 (8.32 to 25.72) respectively. Considering a time lag for a RBCT to be considered an exposure prior to an outcome to limit reverse causation, RBCT was not associated with rejection; the HRs for DCGL attenuated but remained similar. RBCT was also associated with a negative control outcome, demonstrating possible unmeasured confounding. Conclusion RBCT after kidney transplant is not associated with rejection, but may carry an increased risk for DCGL.

Background The lipid-lowering and positive cardiovascular effect of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors was shown in several studies, hence, they are more widely used in the lipid-lowering management of individuals with high cardiovascular risk. As real-world data are still scarce, specifically in patients with type 2 diabetes (T2D), the aim of this retrospective analysis was to investigate the efficacy of PCSK9 inhibitors in lowering low-density lipoprotein cholesterol (LDL-C) in an outpatient clinic of a tertiary care center in routine care. Methods A retrospective analysis of data extracted from the electronic patient record was performed. Patients who were routinely prescribed with PCSK9 inhibitor therapy (alirocumab or evolocumab) during the years 2016 and 2019 were included in the analysis. Characteristics of the patient population, the effects on LDL-C and HbA1c levels as well as subsequent cardiovascular events were assessed over an observation period of 18 months. Results We identified 237 patients treated with PCSK9 inhibitors between January 2016 and September 2019. Almost all patients (97.5%) received PCSK9 inhibitors for secondary prevention. 26.2% of the population had a concomitant diabetes diagnosis. Intolerance to statins (83.1%), ezetimibe (44.7%) or both agents (42.6%) was reported frequently. Three months after initiation of PCSK9 inhibitor therapy, 61.2% of the patients achieved LDL-C levels 54 mmol/mol) had a higher reduction in LDL-C but still were more likely to subsequent cardiovascular events. Conclusions Significant reductions in LDL-C and a high percentage of patients achieving recommended treatment targets were observed. The percentage of patients with T2D meeting recommended LDL-C targets was higher than in those without T2D. Still some patients did not achieve LDL-C levels as recommended in current guidelines. Special attention to the characteristics of these patients is required in the future to enable achievement of treatment goals and avoid adverse cardiovascular outcomes.

The dicentric chromosome (DC) assay accurately quantifies exposure to radiation, however, manual and semi-automated assignment of DCs has limited its use for a potential large-scale radiation incident. The Automated Dicentric Chromosome Identifier and Dose Estimator (ADCI) software automates unattended DC detection and determines radiation exposures, fulfilling IAEA criteria for triage biodosimetry. This study evaluates the throughput of high-performance ADCI (ADCI-HT) to stratify exposures of populations in 15 simulated population scale radiation exposures. ADCI-HT streamlines dose estimation using a supercomputer by optimal hierarchical scheduling of DC detection for varying numbers of samples and metaphase cell images in parallel on multiple processors. We evaluated processing times and accuracy of estimated exposures across census-defined populations. Image processing of 1744 samples on 16,384 CPUs required 1 h 11 min 23 s and radiation dose estimation based on DC frequencies required 32 sec. Processing of 40,000 samples at 10 exposures from five laboratories required 25 h and met IAEA criteria (dose estimates were within 0.5 Gy, median = 0.07). Geostatistically interpolated radiation exposure contours of simulated nuclear incidents were defined by samples exposed to clinically relevant exposure levels (1 and 2 Gy). Analysis of all exposed individuals with ADCI-HT required 0.6–7.4 days, depending on the population density of the simulation.

Die Behandlung von fiebernden Kindern und Jugendlichen nach einer Tropenreise stellt fur den Padiater haufig eine Herausforderung dar. Die genaue Anamnese unter Berucksichtigung des Reiseziels, der Reiseart und moglicher Expositionen (Suswasserexposition, Tierkontakte etc.) sowie eine komplette korperliche Untersuchung sind essenziell. Durch die Verknupfung von Inkubationszeit und Destination lassen sich potenzielle Differenzialdiagnosen haufig deutlich reduzieren. Wahrend viele Infektionen selbstlimitierend oder unkompliziert verlaufen, ist es wichtig, potenziell lebensgefahrliche Infektionen richtig zu erkennen und zugig zu behandeln. Dieser Beitrag soll eine Hilfestellung zur rationalen Herangehensweise und Diagnosestellung bezuglich Fieber im Kontext der tropenmedizinischen Differenzialdiagnosen im padiatrischen Patientenkollektiv geben.

Forschung im Ingenieurwesen (2021). doi:10.1007/s10010-021-00452-3, Published by Springer, Berlin ; Heidelberg

The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease for patients not receiving dialysis represents an update to the KDIGO 2012 guideline on this topic. Development of this guideline update followed a rigorous process of evidence review and appraisal. Guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence. The strength of recommendations is based on the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. The scope includes topics covered in the original guideline, such as optimal blood pressure targets, lifestyle interventions, antihypertensive medications, and specific management in kidney transplant recipients and children. Some aspects of general and cardiovascular health, such as lipid and smoking management, are excluded. This guideline also introduces a chapter dedicated to proper blood pressure measurement since all large randomized trials targeting blood pressure with pivotal outcomes used standardized preparation and measurement protocols adhered to by patients and clinicians. Based on previous and new evidence, in particular the Systolic Blood Pressure Intervention Trial (SPRINT) results, we propose a systolic blood pressure target of less than 120 mm Hg using standardized office reading for most people with chronic kidney disease (CKD) not receiving dialysis, the exception being children and kidney transplant recipients. The goal of this guideline is to provide clinicians and patients a useful resource with actionable recommendations supplemented with practice points. The burden of the recommendations on patients and resources, public policy implications, and limitations of the evidence are taken into consideration. Lastly, knowledge gaps and recommendations for future research are provided.

By 2050, the number of adults over 65 years of age will be double the under-5 population, and heavily concentrated in low- and middle-income countries. Population growth and increasing life expectancies call for effective healthy aging strategies inclusive of immunization to reduce the burden of vaccine-preventable diseases, improve quality of life, and mitigate antimicrobial resistance. Based on a review of available literature on the pneumococcal disease, influenza, and herpes zoster epidemiology and economic burden, and the health systems and policy barriers for adult immunization, we identified evidence gaps and considerations for prioritizing adult immunization. The body of evidence for adult immunization and the health and economic burden of adult disease is heavily concentrated in high-income countries. The few countries reporting adult immunization policies generally focus on high-risk groups. Despite robust child immunization programs in most countries, adult immunization programs and policies lag far behind and there is a general lack of appropriate delivery platforms. Global adult disease burden and economic costs are substantial but evidence from low- and middle-income countries is limited. There is a need for a strengthened evidence base and political commitment to drive a comprehensive, global technical consensus on adult immunization.