A Novel Sensitive Immunoassay Targeting the 5-Methylthio-d-Xylofuranose-Lipoarabinomannan Epitope Meets the WHO's Performance Target for Tuberculosis Diagnosis.

The only currently commercialized point-of-care assay for tuberculosis (TB) that measures lipoarabinomannan (LAM) in urine (Alere LF-LAM) has insufficient sensitivity. We evaluated the potential of 100 novel monoclonal antibody pairs targeting a variety of LAM epitopes on a sensitive electrochemiluminescence platform to improve the diagnostic accuracy. In the screening, many antibody pairs showed high reactivity to purified LAM but performed poorly at detecting urinary LAM in clinical samples, suggesting differences in antigen structure and immunoreactivity of the different LAM sources. The 12 best antibody pairs from the screening were tested in a retrospective case-control study with urine samples from 75 adults with presumptive TB. The best antibody pair reached femtomolar analytical sensitivity for LAM detection and an overall clinical sensitivity of 93% (confidence interval [CI], 80% to 97%) and specificity of 97% (CI, 85% to 100%). Importantly, in HIV-negative subjects positive for TB by sputum smear microscopy, the test achieved a sensitivity of 80% (CI, 55% to 93%). This compares to an overall sensitivity of 33% (CI, 20% to 48%) of the Alere LF-LAM and a sensitivity of 13% (CI, 4% to 38%) in HIV-negative subjects in the same sample set. The capture antibody targets a unique 5-methylthio-d-xylofuranose (MTX)-dependent epitope in LAM that is specific to the Mycobacterium tuberculosis complex and shows no cross-reactivity with fast-growing mycobacteria or other bacteria. The present study provides evidence that improved assay methods and reagents lead to increased diagnostic accuracy. The results of this work have informed the development of a sensitive and specific novel LAM point-of-care assay with the aim to meet the WHO's performance target for TB diagnosis

Optimal Service Placement with QoS Monitoring in NFV and Slicing Enabled 5G IoT Networks

Network function virtualization (NFV) and network slicing are two promising enabling technologies for 5G networks. Considering the volume of data traffic generated by Internet of things (IoT) applications and their service requirement diversity as well as that network resources are spread across different locations, it is imperative to find solutions for optimal service placement and resource allocation for quality of service (QoS) provisioning. In this paper, we address the challenges of optimal network service placement with active QoS monitoring in NFV and network slicing enabled 5G IoT networks and propose a network architecture with optimal computation and resource placement over core, local, and edge data centers. The solution is implemented through virtualized infrastructure managers where operation costs and QoS requirements are considered for service placement. Optimal algorithms are developed based on a control system hub platform with an open source management and orchestration framework. To monitor the performance during traffic runtime, virtual charmed factors are adopted for control and QoS measurement.acceptedVersio

Identification of somatostatin receptor type 5 gene polymorphisms associated with acromegaly

Objective: The aim of this study was to characterize the genetic variance of somatostatin receptor 5 (SSTR5) and investigate the possible correlation of such variants with acromegaly risk and different disease characteristics. Design and methods: The SSTR5 gene coding region and 2000 bp upstream region was sequenced in 48 patients with acromegaly and 96 control subjects. Further, three single nucleotide polymorphisms (SNPs) were analyzed in the same group of acromegaly patients and in an additional group of 475 age- and sex-matched controls. Results: In total, 19 SNPs were identified in the SSTR5 gene locus by direct sequencing. Three SNPs (rs34037914, rs169068, and rs642249) were significantly associated with the presence of acromegaly using the initial controls. The allele frequencies were significantly (P&lt;0.01) different between the acromegaly patients and the additional large control group. rs34037914 and rs642249 remained significantly associated with acromegaly after Bonferroni correction and permutation tests (odds ratio (OR) = 3.38; 95% confidence interval (CI), 1.78-6.42; P=0.00016 and OR=2.41; 95% CI, 1.41-4.13; P=0.0014 respectively). Haplotype reconstruction revealed two possible risk haplotypes determined by rs34037914 (633T) and rs642249 (1044A) alleles. Both haplotypes were found in significantly higher frequency in acromegaly patients compared with controls (P=0.001). In addition, the 663T allele was significantly associated with a younger age of acromegaly diagnosis (unstandardized regression coefficient beta=-10.4; P=0.002), increased body mass index (beta=4.1; P=0.004), higher number of adenoma resection (P&lt;0.001) and lack of observable tumor shrinkage after somatostatin analog treatment (P=0.014). Conclusions: Our results demonstrate a previously undetected strong association of two SSTR5 SNPs with acromegaly. The data also suggest a possible involvement of SSTR5 variants in decreased suppression of GH production and increased tumor proliferation.</p

An RCT of dating matters:Effects on teen dating violence and relationship behaviors

Introduction Teen dating violence is a serious public health problem with few effective prevention strategies. This study examines whether the Dating Matters comprehensive prevention model, compared with a standard of care intervention, prevented negative relationship behaviors and promoted positive relationship behaviors. Study design This longitudinal, cluster-RCT compared the effectiveness of Dating Matters with standard of care across middle school. Standard of care was an evidence-based teen dating violence prevention curriculum (Safe Dates) implemented in eighth grade. Setting/participants Forty-six middle schools in high-risk urban neighborhoods in four U.S. cities were randomized. Schools lost to follow-up were replaced with new schools, which were independently randomized (71% school retention). Students were surveyed in fall and spring of sixth, seventh, and eighth grades (2012–2016). The analysis sample includes students from schools implementing Dating Matters or standard of care for >2 years who started sixth grade in the fall of 2012 or 2013 and had dated (N=2,349 students, mean age 12 years, 49% female, and 55% black, non-Hispanic, 28% Hispanic, 17% other). Intervention Dating Matters is a comprehensive, multicomponent prevention model including classroom-delivered programs for sixth to eighth graders, training for parents of sixth to eighth graders, educator training, a youth communications program, and local health department activities to assess capacity and track teen dating violence–related policy and data. Main outcome measures Self-reported teen dating violence perpetration and victimization, use of negative conflict resolution strategies, and positive relationship skills were examined as outcomes. Imputation and analyses were conducted in 2017. Results Latent panel models demonstrated significant program effects for three of four outcomes; Dating Matters students reported 8.43% lower teen dating violence perpetration, 9.78% lower teen dating violence victimization, and 5.52% lower use of negative conflict resolution strategies, on average across time points and cohorts, than standard of care students. There were no significant effects on positive relationship behaviors. Conclusions Dating Matters demonstrates comparative effectiveness, through middle school, for reducing unhealthy relationship behaviors, such as teen dating violence and use of negative conflict resolution strategies, relative to the standard of care intervention

Targeted Nanoparticles for Imaging Incipient Pancreatic Ductal Adenocarcinoma

Kimberly Kelly and colleagues describe the discovery of plectin-1 as a novel biomarker for pancreatic ductal adenocarcinoma and the subsequent development of a specific imaging probe using this marker

H2A.Bbd: an X-chromosome-encoded histone involved in mammalian spermiogenesis

Despite the identification of H2A.Bbd as a new vertebrate-specific replacement histone variant several years ago, and despite the many in vitro structural characterizations using reconstituted chromatin complexes consisting of this variant, the existence of H2A.Bbd in the cell and its location has remained elusive. Here, we report that the native form of this variant is present in highly advanced spermiogenic fractions of mammalian testis at the time when histones are highly acetylated and being replaced by protamines. It is also present in the nucleosomal chromatin fraction of mature human sperm. The ectopically expressed non-tagged version of the protein is associated with micrococcal nuclease-refractory insoluble fractions of chromatin and in mouse (20T1/2) cell line, H2A.Bbd is enriched at the periphery of chromocenters. The exceedingly rapid evolution of this unique X-chromosome-linked histone variant is shared with other reproductive proteins including those associated with chromatin in the mature sperm (protamines) of many vertebrates. This common rate of evolution provides further support for the functional and structural involvement of this protein in male gametogenesis in mammals

Symptomatic hypopituitarism revealing primary suprasellar lymphoma

<p>Abstract</p> <p>Background</p> <p>The most common cause of hypopituitarism is pituitary adenoma. However, in the case of suprasellar masses different etiologies are possible. We report an unusual case of primary suprasellar lymphoma presented with hypopituitarism.</p> <p>Case presentation</p> <p>A 26 year old woman presented with amenorrhea, galactorrhea and neurological disorders. Also, the laboratory work-up revealed partial hypopituitarism. The magnetic resonance imaging of the head showed a suprasellar mass. A presumptive diagnosis of granulomatous processes was made and the patient was given steroid therapy. Repeated brain MRI detected new lesions in the brain with regression of the suprasellar mass. Stereotactic biopsy of the paraventricular lesion revealed the diagnosis of B-cell lymphoma.</p> <p>Conclusion</p> <p>This case presentation reports a rare cause of hypopituitarism. Primary suprasellar lymphoma is extremely rare and represented a real diagnostic challenge. Besides, suprasellar masses are varied in aetiology and can present diagnostic problems for a radiologist. Also, because of the increased incidence of PCNSL, lymphoma must be kept in mind in the differential diagnosis of lesions in the suprasellar region.</p

Longitudinal SARS-CoV-2 RNA wastewater monitoring across a range of scales correlates with total and regional COVID-19 burden in a well-defined urban population

Wastewater-based epidemiology (WBE) is an emerging surveillance tool that has been used to monitor the ongoing COVID-19 pandemic by tracking SARS-CoV-2 RNA shed into wastewater. WBE was performed to monitor the occurrence and spread of SARS-CoV-2 from three wastewater treatment plants (WWTP) and six neighborhoods in the city of Calgary, Canada (population 1.44 million). A total of 222 WWTP and 192 neighborhood samples were collected from June 2020 to May 2021, encompassing the end of the first-wave (June 2020), the second-wave (November end to December 2020) and the third-wave of the COVID-19 pandemic (mid-April to May 2021). Flow-weighted 24-hour composite samples were processed to extract RNA that was then analyzed for two SARS-CoV-2-specific regions of the nucleocapsid gene, N1 and N2, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Using this approach SARS-CoV-2 RNA was detected in 98.06% (406/414) of wastewater samples. SARS-CoV-2 RNA abundance was compared to clinically diagnosed COVID-19 cases organized by the three-digit postal code of affected individuals' primary residences, enabling correlation analysis at neighborhood, WWTP and city-wide scales. Strong correlations were observed between N1 & N2 gene signals in wastewater and new daily cases for WWTPs and neighborhoods. Similarly, when flow rates at Calgary's three WWTPs were used to normalize observed concentrations of SARS-CoV-2 RNA and combine them into a city-wide signal, this was strongly correlated with regionally diagnosed COVID-19 cases and clinical test percent positivity rate. Linked census data demonstrated disproportionate SARS-CoV-2 in wastewater from areas of the city with lower socioeconomic status and more racialized communities. WBE across a range of urban scales was demonstrated to be an effective mechanism of COVID-19 surveillance

Many quality measurements, but few quality measures assessing the quality of breast cancer care in women: A systematic review

BACKGROUND: Breast cancer in women is increasingly frequent, and care is complex, onerous and expensive, all of which lend urgency to improvements in care. Quality measurement is essential to monitor effectiveness and to guide improvements in healthcare. METHODS: Ten databases, including Medline, were searched electronically to identify measures assessing the quality of breast cancer care in women (diagnosis, treatment, followup, documentation of care). Eligible studies measured adherence to standards of breast cancer care in women diagnosed with, or in treatment for, any histological type of adenocarcinoma of the breast. Reference lists of studies, review articles, web sites, and files of experts were searched manually. Evidence appraisal entailed dual independent assessments of data (e.g., indicators used in quality measurement). The extent of each quality indicator's scientific validation as a measure was assessed. The American Society of Clinical Oncology (ASCO) was asked to contribute quality measures under development. RESULTS: Sixty relevant reports identified 58 studies with 143 indicators assessing adherence to quality breast cancer care. A paucity of validated indicators (n = 12), most of which assessed quality of life, only permitted a qualitative data synthesis. Most quality indicators evaluated processes of care. CONCLUSION: While some studies revealed patterns of under-use of care, all adherence data require confirmation using validated quality measures. ASCO's current development of a set of quality measures relating to breast cancer care may hold the key to conducting definitive studies