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Background There is limited evidence to evaluate screening algorithms with rapid antigen testing and exposure assessments as identification strategies for paucisymptomatic or asymptomatic Ebola virus (EBOV) infection and unrecognized EBOV disease (EVD). Methods We used serostatus and self-reported postexposure symptoms from a cohort study to classify contact-participants as having no infection, paucisymptomatic or asymptomatic infection, or unrecognized EVD. Exposure risk was categorized as low, intermediate, or high. We created hypothetical scenarios to evaluate the World Health Organization (WHO) case definition with or without rapid diagnostic testing (RDT) or exposure assessments. Results This analysis included 990 EVD survivors and 1909 contacts, of whom 115 (6%) had paucisymptomatic or asymptomatic EBOV infection, 107 (6%) had unrecognized EVD, and 1687 (88%) were uninfected. High-risk exposures were drivers of unrecognized EVD (adjusted odds ratio, 3.5 [95% confidence interval, 2.4–4.9]). To identify contacts with unrecognized EVD who test negative by the WHO case definition, the sensitivity was 96% with RDT (95% confidence interval, 91%–99%), 87% with high-risk exposure (82%–92%), and 97% with intermediate- to high-risk exposures (93%–99%). The proportion of false-positives was 2% with RDT and 53%–93% with intermediate- and/or high-risk exposures. Conclusion We demonstrated the utility and trade-offs of sequential screening algorithms with RDT or exposure risk assessments as identification strategies for contacts with unrecognized EVD. [ABSTRACT FROM AUTHOR]

Do medical facilities also help advance improvements in socio-economic outcomes? We focus on Veterans, a vulnerable group over the COVID-19 pandemic who have access to a comprehensive healthcare network, and the receipt of funds from the Paycheck Protection Program (PPP) between April and June as a source of variation. First, we find that Veterans received 3.5% more loans and 6.8% larger loans than their counterparts (p < 0.01), controlling for a wide array of zipcode characteristics. Second, we develop models to predict the number of PPP loans awarded to Veterans, finding that the inclusion of local VA medical center characteristics adds almost as much explanatory power as the industry and occupational composition in an area and even more than the education, race, and age distribution combined. Our results suggest that VA medical centers can play an important role in helping Veterans thrive even beyond addressing their direct medical needs. [ABSTRACT FROM AUTHOR]

Introduction and objectives: Adult undescended testicles (UDTs) often present to fertility specialists with subfertility or azoospermia and with either an intra‐abdominal or inguinal testicle(s). Performing an orchidopexy followed by a surgical sperm retrieval (SSR) is a potential option to retrieve spermatozoa. A microdissection TESE (mTESE) procedure is performed to retrieve mature spermatozoa for use in ICSI. This paper reviews the outcomes of mTESE in adults following an orchidopexy. Material and methods: A cohort of azoospermic patients underwent adult orchidopexy over a 10‐year period at a single specialist centre. Data were collected retrospectively from the patient records retrieved from an institutional database. All patients underwent pre‐operative imaging to localize the testicles, serum testosterone levels and a semen analysis. Separate intraoperative testicular biopsies were performed to exclude intratubular germ cell neoplasia (ITGCN) and to analyse the Johnsen score. Results: Twelve patients (age range 18–36 years) underwent orchidopexy procedures for either intra‐abdominal or inguinal testicles. Mean follow‐up was 34 months (range 13–58). Ninety per cent of patients had bilateral UDT with azoospermia. Pre‐operative testosterone levels were within the normal range (mean 13.9 nmol/L; range 9.1–24.2). Five pelvic testicles (from four patients) were brought down and underwent a delayed mTESE. A total of nine inguinal orchidopexy procedures were carried out in eight men, and spermatozoa were found and preserved in three patients. None of the men with intra‐abdominal testicles had mature spermatozoa present following a delayed mTESE. Overall, SSR was successful in 37.5% of the patients. Histological analysis showed no cases of ITGCN and the Johnsen scores ranged from 1 to 3.3. Conclusions: Microdissection TESE following orchidopexy for inguinal testicles can result in a successful SSR in over 1/3rd of patients. Intra‐abdominal testicles appear to lack spermatogonia although the testicles can still be preserved for endogenous hormone production. Adult orchidopexy allows preservation of endogenous testosterone, easier self‐examination and an immediate or delayed mTESE in azoospermic patients. [ABSTRACT FROM AUTHOR]

Background: A lack of consensus exists amongst national guidelines regarding who should be investigated for haematuria. Type of haematuria and age-specific thresholds are frequently used to guide referral for the investigation of haematuria.Objectives: To develop and externally validate the haematuria cancer risk score (HCRS) to improve patient selection for the investigation of haematuria.Methods: Development cohort comprise of 3539 prospectively recruited patients recruited at 40 UK hospitals (DETECT 1; ClinicalTrials.gov: NCT02676180) and validation cohort comprise of 656 Swiss patients. All patients were aged >18 years and referred to hospital for the evaluation of visible and nonvisible haematuria. Sensitivity and specificity of the HCRS in the validation cohort were derived from a cut-off identified from the discovery cohort.Results: Patient age, gender, type of haematuria and smoking history were used to develop the HCRS. HCRS validation achieves good discrimination (AUC 0.835; 95% CI: 0.789-0.880) and calibration (calibration slope = 1.215) with no significant overfitting (P = 0.151). The HCRS detected 11.4% (n = 8) more cancers which would be missed by UK National Institute for Health and Clinical Excellence guidelines. The American Urological Association guidelines would identify all cancers with a specificity of 12.6% compared to 30.5% achieved by the HCRS. All patients with upper tract cancers would have been identified.Conclusion: The HCRS offers good discriminatory accuracy which is superior to existing guidelines. The simplicity of the model would facilitate adoption and improve patient and physician decision-making. [ABSTRACT FROM AUTHOR]

Estimating the 3-D pose of instruments is an important part of robotic minimally invasive surgery for automation of basic procedures as well as providing safety features, such as virtual fixtures. Image-based methods of 3-D pose estimation provide a non-invasive low cost solution compared with methods that incorporate external tracking systems. In this paper, we extend our recent work in estimating rigid 3-D pose with silhouette and optical flow-based features to incorporate the articulated degrees-of-freedom (DOFs) of robotic instruments within a gradient-based optimization framework. Validation of the technique is provided with a calibrated ex-vivo study from the da Vinci Research Kit (DVRK) robotic system, where we perform quantitative analysis on the errors each DOF of our tracker. Additionally, we perform several detailed comparisons with recently published techniques that combine visual methods with kinematic data acquired from the joint encoders. Our experiments demonstrate that our method is competitively accurate while relying solely on image data. [ABSTRACT FROM PUBLISHER]

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Common bean (Phaseolus vulgaris L.) is an important constituent of people's diets especially in developing countries. Dry beans find a suitable position in the culinary items because of their high nutritional value. For instance, rice and bean recipe (Rajmah Chawal) is famous in the northern part of India. Many fungal, viral and bacterial diseases affect the crop and causes heavy losses worldwide. Among the various fungal diseases, bean anthracnose caused by Colletotrichum lindemuthianum is a serious disease under cool and humid environments. Under favorable conditions, the yield losses may be up to 100 percent. The scientific community across the world has been studying the bean-anthracnose interaction for over 100 years and the information has helped to understand the pathosystem and devise better disease management strategies. Many excellent reviews on anthracnose resistance genes, marker aided breeding and R gene signatures highlight different tactics for disease management. Assembling the substantial literature available on pathogen is necessary for better understanding of the pathogen biology. The present review consolidates this information and provides a comprehensive outline about the detection, pathogenicity genes, pathogenic variability and molecular diversity of C. lindemuthianum. The importance of the bean genome and availability of SNP markers to dissect the bean-anthracnose interface is also addressed. [ABSTRACT FROM AUTHOR]

Common bean (Phaseolus vulgaris L.) production is subject to prolonged and crop-failurethreatening drought events worldwide. One of the best approaches in identifying parents and progeny with local adaptation to a target environment is the characterization of multiple environments. In this study, we used genotype plus genotype ' environment (GGE) biplot analysis to examine the informativeness of the testing environments used by the bean breeding program at Michigan State University to select for drought tolerance. A group of 96 diverse Mesoamerican common bean genotypes assembled from breeding programs and germplasm collections across the United States were tested in two Michigan locations for 3 yr. Genotype plus genotype ' environment biplots were used to rank genotypes according to environments and treatments (irrigated and rainfed) within environments. A genotype ' trait analysis was also used to identify traits relevant to yield under rainfed and irrigated environments. Significant differentiation and nonredundancy were found among the environments, suggesting that resource use is efficient. Rainfed environments were better at discriminating high-performing genotypes in Michigan. Genotype ' trait analysis showed a significantly negative correlation between growth habit and seed yield. A common feature of the better adapted and higher yielding genotypes under Michigan conditions was the upright type II growth habit. A number of root architecture traits such as taproot diameter were independent or associated with yield in common bean under different environments. Genotypes with contrasting traits associated with yield under rainfed and irrigated conditions were identified and could be used in the development of future common bean cultivars with improved drought tolerance. [ABSTRACT FROM AUTHOR]

Background: The accuracy of prostate-specific antigen (PSA) testing in prostate cancer detection is constrained by low sensitivity and specificity. Dysregulated expression of minichromosome maintenance (Mcm) 2-7 proteins is an early event in epithelial multistep carcinogenesis and thus MCM proteins represent powerful cancer diagnostic markers. In this study we investigate Mcm5 as a urinary biomarker for prostate cancer detection.Methods: Urine was obtained from 88 men with prostate cancer and from two control groups negative for malignancy. A strictly normal cohort included 28 men with complete, normal investigations, no urinary calculi and serum PSA <2 ng ml(-1). An expanded control cohort comprised 331 men with a benign final diagnosis, regardless of PSA level. Urine was collected before and after prostate massage in the cancer patient cohort. An immunofluorometric assay was used to measure Mcm5 levels in urine sediments.Results: The Mcm5 test detected prostate cancer with 82% sensitivity (confidence interval (CI)= 72-89%) and with a specificity ranging from 73 (CI=68-78%) to 93% (CI=76-99%). Prostate massage led to increased Mcm5 signals compared with pre-massage samples (median 3440 (interquartile range (IQR) 2280 to 5220) vs 2360 (IQR <1800 to 4360); P=0.009), and was associated with significantly increased diagnostic sensitivity (82 vs 60%; P=0.012).Conclusions: Urinary Mcm5 detection seems to be a simple, accurate and noninvasive method for identifying patients with prostate cancer. Large-scale prospective trials are now required to evaluate this test in diagnosis and screening. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer is the second most common cancer of the urinary system. Early diagnosis of this tumour and estimation of risk of future progression after initial transuretherial resection have a significant impact on prognosis. Although there are several molecular markers for the diagnosis and prognosis for this tumour, their accuracy is not ideal. Previous reports have shown that UHRF1 (ubiquitin-like with PHD and ring-finger domains 1) is essential for cellular proliferation. In this study, we examined whether UHRF1 can be a novel molecular marker of bladder cancer.Methods: We performed real-time TaqMan quantitative reverse transcription-PCR and immunohistochemistry to examine expression levels of UHRF1 in bladder and kidney cancers.Results: Significant overexpression of UHRF1 was observed in bladder cancer. The overexpression was correlated with the stage and grade of the cancer. Although UHRF1 expression in muscle-invasive cancer was greater than in non-invasive (pTa) or superficially invasive (pT1) cancers, UHRF1 could still be detected by immunohistochemistry in these early-stage cancers. Overexpression of UHRF1 in bladder cancer was associated with increased risk of progression after transurethral resection. High expression of UHRF1 in kidney cancer was also observed. But the increased levels of UHRF1 in kidney cancer were less significant compared with those in bladder cancer.Conclusion: Our result indicates that an immunohistochemistry-based UHRF1 detection in urine sediment or surgical specimens can be a sensitive and cancer-specific diagnostic and/or prognosis method, and may greatly improve the current diagnosis based on cytology. [ABSTRACT FROM AUTHOR]

Membrane type-1 matrix metalloproteinase (MT1-MMP) is a zinc-binding endopeptidase, which plays a crucial role in tumour growth, invasion and metastasis. We have shown previously that MT1-MMP has higher expression levels in the human urothelial cell carcinoma (UCC) tissue. We show here that siRNA against MT1-MMP blocks invasion in UCC cell lines. Invasion is also blocked by broad-spectrum protease and MMP inhibitors including tissue inhibitor of metalloproteinase-1 and -2. Membrane type-1-MMP can also regulate transcription. We have used expression arrays to identify genes that are differentially transcribed when siRNA is used to suppress MT1-MMP expression. Upon MT1-MMP knockdown, Dickkopf-3 (DKK3) expression was highly upregulated. The stability of DKK3 mRNA was unaffected under these conditions, suggesting transcriptional regulation of DKK3 by MT1-MMP. Dickkopf-3 has been previously shown to inhibit invasion. We confirm that the overexpression of DKK3 leads to decreased invasive potential as well as delayed wound healing. We show for the first time that the effects of MT1-MMP on cell invasion are mediated in part through changes in DKK3 gene transcription. [ABSTRACT FROM AUTHOR]

Activation of mitogen/extracellular-signal-regulated kinase kinase 5/extracellular signal-regulated kinase-5 (MEK5/ERK5) growth signalling is coupled to increased cell proliferation in prostate cancer (PCa). Dysregulation of the DNA replication licensing pathway, a critical step in growth control downstream of transduction signalling pathways, is associated with development of PCa. In this study we have investigated linkages between the MEK5/ERK5 pathway and DNA replication licensing during prostate carcinogenesis. The effects of increased MEK5/ERK5 signalling on the expression of replication licensing factors Mcm2 and geminin and the proliferation marker Ki67 were studied in an ecdysone-inducible system expressing a constitutively activated mutant of MEK5 in EcR293 cells and in stable ERK5 over-expressing PC3 clones. In parallel, expression of these biomarkers in PCa biopsy specimens (n=58) was studied and compared to clinicopathological parameters. In both in vitro systems induction of MEK5 expression resulted in increased levels of phosphorylated ERK5 and Mcm2, geminin and Ki67 proteins. In PCa specimens average Mcm2 expression was greater than Ki67 and geminin expression (median labelling index (LI) 36.7, 18.1, and 3.4% respectively), consistent with their differential expression according to growth status (P<0.0001). Mcm2, geminin and Ki67 expression were significantly associated with Gleason grade (P=0.0002, P=0.0003, P=0.004); however there was no link with T or M stage. There was a significant relationship between increasing ERK5 expression and increasing Mcm2 (P=0.003) and Ki67 (P=0.009) expression, with non-significant trends seen with increasing MEK5 expression. There were significant associations between Gleason grade and the number of cells traversing G1 phase (Ki67LI-gemininLI; (P=0.001)), with high ERK5 levels associated with both an increase in replication licensed but non-cycling cells (Mcm2LI-Ki67LI; (P=0.01)) and accelerated cell cycle progression (gemininLI/Ki67LI; (P= 0.005)), all indicative of a shift towards increasing proliferative potential. While Mcm2 and Ki67 were both prognostic factors on univariate analysis, only Mcm2 remained an independent prognostic marker on multivariate analysis. Taken together, our data show that induction of MEK5/ERK5 signalling is linked to activation of the DNA replication licensing pathway in PCa, and that the strong prognostic value of MCM proteins may result from their function as relay stations coupling growth regulatory pathways to genome duplication.British Journal of Cancer (2007) 96, 1384–1393. doi:10.1038/sj.bjc.6603718 www.bjcancer.com Published online 3 April 2007 [ABSTRACT FROM AUTHOR]

Pathogenicity of physiologically distinct races of Colletotrichum lindemuthianum originating from Andean (races 7, 19 and 55) and Mesoamerican (races 9, 31, 65, 69, 73, 81, 89, 95 and 453) locations of the new world were evaluated on 26 landrace genotypes of common bean ( Phaseolus vulgaris L.) from Paraná State, Brazil. Races 7 (Andean), 65, 73 and 89 (Mesoamerican) were the most pathogenic, while race 31 (Mesoamerican) was the least pathogenic. Most of the landrace genotypes evaluated (88%) were resistant to race 31, except Carioca 3, Preto 1 and Preto 2. In addition, about 50% of the landrace genotypes had resistance to races 9, 19, 55 and 453; and about 30% to races 7, 65, 69, 73, 81, 89 and 95. The resistance index, which measured the pathogenicity response averaged across all the physiologically distinct Andean and Mesoamerican races of C. lindemuthianum, of the landrace genotypes ranged from 8% to 83%. The most resistant cultivars were Carioca Pintado 1, Carioca Pintado 2, Jalo Vermelho and Jalo de Listras Pretas. In contrast, the most susceptible cultivars were Jalo Pardo, Jalo Pintado 1 and Bolinha that showed resistance only to the least pathogenic race 31. These results indicated that many of the common bean landrace cultivars evaluated have genes that could be useful in breeding programmes to enhance resistance to Andean and Mesoamerican races of C. lindemuthianum. [ABSTRACT FROM AUTHOR]

The matrix metalloproteinases (MMPs) are endopeptidases which break down the extracellular matrix and regulate cytokine and growth factor activity. Several MMPs have been implicated in the promotion of invasion and metastasis in a broad range of tumours including urothelial carcinoma. In this study, RNA from 132 normal bladder and urothelial carcinoma specimens was profiled for each of the 24 human MMPs, the four endogenous tissue inhibitors of MMPs (TIMPs) and several key growth factors and their receptors using quantitative real time RT-PCR. Laser capture microdissection (LCM) of RNA from 22 tumour and 11 normal frozen sections was performed allowing accurate RNA extraction from either stromal or epithelial compartments. This study confirms the over expression in bladder tumour tissue of well-documented MMPs and highlights a range of MMPs which have not previously been implicated in the development of urothelial cancer. In summary, MMP-2, MT1-MMP and the previously unreported MMP-28 were very highly expressed in tumour samples while MMPs 1, 7, 9, 11, 15, 19 and 23 were highly expressed. There was a significant positive correlation between transcript expression and tumour grade for MMPs 1, 2, 8, 10, 11, 12, 13, 14, 15 and 28 (P < 0.001). At the same confidence interval, TIMP-1 and TIMP-3 also correlated with increasing tumour grade. LCM revealed that most highly expressed MMPs are located primarily within the stromal compartment except MMP-13 which localised to the epithelial compartment. This work forms the basis for further functional studies, which will help to confirm the MMPs as potential diagnostic and therapeutic targets in early bladder cancer. [ABSTRACT FROM AUTHOR]

Background and objective: Hypotension, the commonest side-effect of spinal anaesthesia, results from sympathetic denervation. This study compared patient positioning (supine vs. decubitus) on haemodynamic variables during spinal anaesthesia. Methods: After intravenous crystalloid preloading with 5 mL kg -1 , hyperbaric bupivacaine 0.5% 2.5 mL was injected intrathecally at the L2-3 or L3-4 interspace. Patients were then randomly assigned to be positioned immediately supine and horizontal for 30 min (Group SUP, n = 12), or remained in the lateral decubitus position (fractured hip dependent) for 30 min (Group LAT, n = 14). Systolic blood pressure, mean arterial pressure, and loss of sensation of pinprick sensation were recorded prior to induction of spinal anaesthesia (baseline) and at 1, 2, 3, 5, 10, 15, 30, 45, 60, 90 and 120 min after intrathecal injection. Results: In Group SUP, the percent maximum systolic blood pressure (36 ± 13%) and percent maximum mean arterial pressure decreases (27 ± 13%) were significantly greater (P < 0.05) than in Group LAT (30 ± 8% and 23 ± 11%, respectively). Additionally, there was a borderline significant delay in the time to maximum systolic blood pressure decrease in Group LAT (3H ± 30 min) when compared with Group SUP (20 ± 17 min, P = 0.06), while the total dose of ephedrine required in the SUP group (30 mg) was greater than that requited in the LAT group (15 mg, P = 0.05). In Group LAT patients, the mean level of denervation on the operative side extended 2 dermatomes more cephalad than in Group SUP. Conclusions: Lateral positioning for spinal anaesthesia delays the onset of hypotension, while requiring smaller total doses of vasoconstrictors for blood pressure maintenance. [ABSTRACT FROM AUTHOR]

Interferon alpha (IFNalpha) is used to treat patients with advanced renal cell carcinoma (RCC) despite limited clinical benefit. IFNalpha can induce Fas receptor-mediated apoptosis by direct activation of pro-caspase-8 followed by activation of caspase-3. Alternative, indirect activation of caspase-3 via mitochondrial release of cytochrome c can occur and may explain the rescue from Fas-activated cell death by the antiapoptotic members of the Bcl-2 family. In this study, we examined G3139, a novel antisense compound targeting Bcl-2, in combination with IFNalpha. Human RCC lines (SK-RC-44 and SK-RC-07) were treated with IFNalpha, G3139 or a combination of the two. Fas-mediated cytotoxicity was induced by anti-Fas mAb, CH11. An analysis of Bcl-2, Fas and the cleavage of PARP was performed. IFNalpha induced Fas and Bcl-2 in SK-RC-44 and SK-RC-07. IFNalpha sensitised SK-RC-44 to anti-Fas and induced PARP cleavage confirming that IFNalpha has a cytotoxic effect on RCC lines by induction of the Fas antigen. Cytotoxicity was not evident in SK-RC-07 cells treated with IFNalpha. G3139 induced a specific downregulation of Bcl-2 in SK-RC-07 cells, which were then sensitised to anti-Fas after treatment with IFNalpha. Taken together, these results suggest that Fas-dependent pathways as well as alternative pathways, which can be inhibited by Bcl-2, exist in renal cell carcinoma. G3139 in combination with IFNalpha is a potential therapy in patients with metastatic renal cell carcinoma. [ABSTRACT FROM AUTHOR]