Spatio-temporal changes of winter and spring phytoplankton blooms in Arabian sea during the period 1997-2020.

Arabian Sea (AS) experiences Chlorophyll-a (Chl-a) blooms during winter and early spring (November-March) mainly due to the changes induced by seasonally reversing monsoon winds and associated processes. The seasonal blooms exhibit distinct regional patterns in their onset, duration, intensity and peak period. Recent changes in ocean dynamics and plankton composition have inflicted adverse effects in the distribution of Chl-a concentration in AS. Here, we analyse the long-term spatio-temporal changes in winter and early spring bloom events during the period 1997-2020, and evaluate the role of sea surface temperature (SST), mixed layer depth (MLD), sea surface salinity, winds, mesoscale eddies and surface currents on these bloom occurrences. We observe a significant reduction in these blooms, which started in the early 2000s and intensified in the last decade (2010-2020), with a notable drop in the adjacent gulfs (Gulf of Aden: 1.38 ± 0.7 × 10-5 mg m-3 yr-1, Gulf of Oman: 4.71 ± 1.35 × 10-6 mg m-3 yr-1) and West coast of India (-6.71 ± 2.85 × 10-6 mg m-3 yr-1). The MLD and ocean temperature are the major factors that govern bloom in Gulf of Oman and open waters. Conversely, the coastal upwelling and eddies drive blooms in Gulf of Aden. The winter cooling trigger the bloom in the northern Indian west coast, but the inter-basin exchange of surface waters through the West Indian Coastal Current inhibits its southward spread. This study, therefore, reveals unique processes that initiate and control the winter and early spring blooms in different regions of AS. The ongoing warming of AS could contribute to further decline in these seasonal blooms, which would be a great concern for regional marine productivity and associated regional food security.

Genetic landscape of pancreatic adenocarcinoma patients: a pilot study from Pakistan.

BACKGROUND: Pancreatic adenocarcinoma is one of the most aggressive malignancies with extremely low survival rate. Studies have shown that the exploration of key genes can provide a basis for targeted treatment of these patients. The genomic architecture of the Pakistani pancreatic adenocarcinoma patients remains unexplored. Keeping the scenario in place, the current study aims to analyse 88 cancer related genes in Pakistani pancreatic adenocarcinoma patients in order to elucidate candidate gene(s) for targeted molecular therapy. METHODS AND RESULTS: A total 18 patients were included in the study initially and FFPE tumor samples were obtained. After confirmation of diagnosis and appropriate tumor content, DNA was extracted. Based on the quality and quantity of the extracted DNA, six pancreatic adenocarcinoma tumor samples were selected. Following to this, all the samples were subjected to targeted sequencing (Axen Cancer Panel 1). Variant detection was done and clinical significance of identified variants was assessed using ClinVar database. Targeted sequencing of tumor samples revealed a total of 29 alterations in the coding region of various genes. Among these five pathogenic variants were found in KRAS, BRCA1, TP53 and APC genes. CONCLUSION: This is the first study that explores genes involved in pancreatic adenocarcinoma from the Pakistani population. Results obtained from the pilot study can guide us about the key genetic players in the Pakistani pancreatic adenocarcinoma population. This can lead to our better understanding of the molecular targeted therapies for these patients and designing future researches on larger sample size.

A user-guided personalization methodology to facilitate new smart home occupancy.

Smart homes are becoming increasingly popular in providing people with the services they desire. Activity recognition is a fundamental task to provide personalised home facilities. Many promising approaches are being used for activity recognition; one of them is data-driven. It has some fascinating features and advantages. However, there are drawbacks such as the lack of ability to providing home automation from the day one due to the limited data available. In this paper, we propose an approach, called READY (useR-guided nEw smart home ADaptation sYstem) for developing a personalised automation system that provides the user with smart home services the moment they move into their new house. The system development process was strongly user-centred, involving users in every step of the system's design. Later, the user-guided transfer learning approach was introduced that uses an old smart home data set to enhance the existing smart home service with user contributions. Finally, the proposed approach and designed system were tested and validated in the smart lab that showed promising results.

Henoch-Schönlein purpura: Another COVID-19 complication.

Whether affecting children or adults, SARS-CoV-2 infection (COVID-19) can have multi-organ involvement mediated by an inflammatory cascade. Immunoglobulin A (IgA) is one of the key components of the inflammatory cascade that can lead to endothelial injury and inflammation. IgA vasculitis or Henoch-Schönlein purpura (HSP) has been rarely reported in the context of COVID-19. In this report, we highlight a case of HSP occurring 2 days after diagnosis of COVID-19 in a 16-year-old boy, who presented with palpable purpura of the lower extremities and buttocks, diffuse abdominal pain, hemoptysis, and hematochezia. He was treated with oral prednisolone with rapid clinical improvement.

Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer.

BACKGROUND: Microsatellite instability (MSI) is a biomarker for response to immune checkpoint inhibitors (ICPIs). PD-1 inhibitors in metastatic colorectal carcinoma (mCRC) with MSI-high (MSI-H) have demonstrated a high disease control rate and favorable progression-free survival (PFS); however, reported response rates to pembrolizumab and nivolumab are variable and often <50%, suggesting that additional predictive biomarkers are needed. METHODS: Clinicopathologic data were collected from patients with MSI-H mCRC confirmed by hybrid capture-based next-generation sequencing (NGS) treated with PD-1/L1 inhibitors at five institutes. Tumor mutational burden (TMB) was determined on 0.8-1.1 Mb of sequenced DNA and reported as mutations/Mb. Potential biomarkers of response and time to progression were analyzed by univariate and multivariate analyses. Once TMB was confirmed as a predictive biomarker, a larger dataset of 18 140 unique CRC patients was analyzed to define the relevance of the identified TMB cut-point. RESULTS: A total of 22 patients were treated with PD-1/L1 inhibitors including 19 with pembrolizumab monotherapy. Among tested variables, TMB showed the strongest association with objective response (OR; P < 0.001) and PFS, by univariate (P < 0.001) and multivariate analysis (P < 0.01). Using log-rank statistics, the optimal predictive cut-point for TMB was estimated between 37 and 41 mutations/Mb. All 13 TMBhigh cases responded, while 6/9 TMBlow cases had progressive disease. The median PFS for TMBhigh has not been reached (median follow-up >18 months) while the median PFS for TMBlow was 2 months. A TMB of 37.4 mutations/Mb in a large MSI-H mCRC population (821/18, 140 cases; 4.5%) evaluated by NGS corresponded to the 35th percentile cut-point. CONCLUSIONS: TMB appears to be an important independent biomarker within MSI-H mCRC to stratify patients for likelihood of response to ICPIs. If validated in prospective studies, TMB may play an important role in guiding the sequencing and/or combinations of ICPIs in MSI-H mCRC.

Loss of function of NF1 is a mechanism of acquired resistance to endocrine therapy in lobular breast cancer.

Background: Invasive lobular carcinoma (ILC) as a disease entity distinct from invasive ductal carcinoma (IDC) has merited focused studies of the genomic landscape, but those to date are largely limited to the assessment of early-stage cancers. Given that genomic alterations develop as acquired resistance to endocrine therapy, studies on refractory ILC are needed. Patients and methods: Tissue from 336 primary-enriched, breast-biopsied ILC and 485 estrogen receptor (ER)-positive IDC and metastatic biopsy specimens from 180 ILC and 191 ER-positive IDC patients was assayed with hybrid-capture-based comprehensive genomic profiling for short variant, indel, copy number variants, and rearrangements in up to 395 cancer-related genes. Results: Whereas ESR1 alterations are enriched in the metastases of both ILC and IDC compared with breast specimens, NF1 alterations are enriched only in ILC metastases (mILC). NF1 alterations are predominantly under loss of heterozygosity (11/14, 79%), are mutually exclusive with ESR1 mutations [odds ratio = 0.24, P < 0.027] and are frequently polyclonal in ctDNA assays. Assessment of paired specimens shows that NF1 alterations arise in the setting of acquired resistance. An in vitro model of CDH1 mutated ER-positive breast cancer demonstrates that NF1 knockdown confers a growth advantage in the presence of 4-hydroxy tamoxifen. Our study further identified a significant increase in tumor mutational burden (TMB) in mILCs relative to breast ILCs or metastatic IDCs (8.9% >20 mutations/mb; P < 0.001). Most TMB-high mILCs harbor an APOBEC trinucleotide signature (14/16; 88%). Conclusions: This study identifies alteration of NF1 as enriched specifically in mILC. Mutual exclusivity with ESR1 alterations, polyclonality in relapsed ctDNA, and de novo acquisition suggest a role for NF1 loss in endocrine therapy resistance. Since NF1 loss leads to RAS/RAF kinase activation, patients may benefit from a matched inhibitor. Moreover, for an independent subset of mILC, TMB was elevated relative to breast ILC, suggesting possible benefit from immune checkpoint inhibitors.

Recurrent hyperactive ESR1 fusion proteins in endocrine therapy-resistant breast cancer.

Background: Estrogen receptor-positive (ER-positive) metastatic breast cancer is often intractable due to endocrine therapy resistance. Although ESR1 promoter switching events have been associated with endocrine-therapy resistance, recurrent ESR1 fusion proteins have yet to be identified in advanced breast cancer. Patients and methods: To identify genomic structural rearrangements (REs) including gene fusions in acquired resistance, we undertook a multimodal sequencing effort in three breast cancer patient cohorts: (i) mate-pair and/or RNAseq in 6 patient-matched primary-metastatic tumors and 51 metastases, (ii) high coverage (>500×) comprehensive genomic profiling of 287-395 cancer-related genes across 9542 solid tumors (5216 from metastatic disease), and (iii) ultra-high coverage (>5000×) genomic profiling of 62 cancer-related genes in 254 ctDNA samples. In addition to traditional gene fusion detection methods (i.e. discordant reads, split reads), ESR1 REs were detected from targeted sequencing data by applying a novel algorithm (copyshift) that identifies major copy number shifts at rearrangement hotspots. Results: We identify 88 ESR1 REs across 83 unique patients with direct confirmation of 9 ESR1 fusion proteins (including 2 via immunoblot). ESR1 REs are highly enriched in ER-positive, metastatic disease and co-occur with known ESR1 missense alterations, suggestive of polyclonal resistance. Importantly, all fusions result from a breakpoint in or near ESR1 intron 6 and therefore lack an intact ligand binding domain (LBD). In vitro characterization of three fusions reveals ligand-independence and hyperactivity dependent upon the 3' partner gene. Our lower-bound estimate of ESR1 fusions is at least 1% of metastatic solid breast cancers, the prevalence in ctDNA is at least 10× enriched. We postulate this enrichment may represent secondary resistance to more aggressive endocrine therapies applied to patients with ESR1 LBD missense alterations. Conclusions: Collectively, these data indicate that N-terminal ESR1 fusions involving exons 6-7 are a recurrent driver of endocrine therapy resistance and are impervious to ER-targeted therapies.

Severe localised granulomatosis with polyangiitis (Wegener's granulomatosis) manifesting with extensive cranial nerve palsies and cranial diabetes insipidus: a case report and literature review.

BACKGROUND: Granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis) is a multisystem vasculitis of small- to medium-sized blood vessels. Cranial involvement can result in cranial nerve palsies and, rarely, pituitary infiltration. CASE PRESENTATION: We describe the case of a 32 year-old woman with limited but severe GPA manifesting as progressive cranial nerve palsies and pituitary dysfunction. Our patient initially presented with localised ENT involvement, but despite treatment with methotrexate, she deteriorated. Granulomatous inflammatory tissue around the skull base resulted in cavernous sinus syndrome, facial nerve palsy, palsies of cranial nerves IX-XII (Collet-Sicard syndrome), and the rare complication of cranial diabetes insipidus due to pituitary infiltration. The glossopharyngeal, vagus and accessory nerve palsies resulted in severe dysphagia and she required nasogastric tube feeding. Her neurological deficits substantially improved with treatment including high dose corticosteroid, cyclophosphamide and rituximab. CONCLUSIONS: This case emphasises that serious morbidity can arise from localised cranial Wegener's granulomatosis in the absence of systemic disease. In such cases intensive induction immunosuppression is required. Analysis of previously reported cases of pituitary involvement in GPA reveals that this rare complication predominantly affects female patients.

Comprehensive genomic profiling of salivary mucoepidermoid carcinomas reveals frequent BAP1, PIK3CA, and other actionable genomic alterations.

Background: We sought to identify genomic alterations (GAs) in salivary mucoepidermoid carcinomas. Patients and methods: DNA was extracted from 48 mucoepidermoid carcinomas. Comprehensive genomic profiling (CGP) including the calculation to tumor mutational burden (TMB) was performed on hybridization-captured adaptor ligation-based libraries of 315 cancer-related genes plus introns from 28 genes frequently rearranged for cancer and evaluated for all classes of GAs. Results: A total of 183 GAs were found in 80 unique genes. High-grade tumors had more GAs (mean 5 ± 3.8) compared with low (2.3 ± 1.4) or intermediate (2.6 ± 1.5) (P = 0.019). TP53 GAs were seen in all tumor grades (41.7%) but were most common in high-grade malignancies (56%) (P = 0.047). CDKN2A GAs were seen in 41.6% of tumors. PI3K/mTOR pathway activation, including PI3KCA mutations, were more common in high grade (52%) than in low- and intermediate-grade tumors (4.3%) (P = 0.007). BAP1 GAs were observed in 20.8% of tumors and BRCA1/2 GAs present in 10.5% of specimens. ERBB2 amplifications were seen in only 8.3% of tumors. The TMB for this patient group was relatively low with only 5 (10%) of cases having greater than 10 mutations/megabase of sequenced DNA. Conclusion: CGP of salivary mucoepidermoid carcinomas revealed diverse GAs that may lead to customized treatment options for patients with these rare tumors.

Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer.

BACKGROUND: Genomic changes that occur in breast cancer during the course of disease have been informed by sequencing of primary and metastatic tumor tissue. For patients with relapsed and metastatic disease, evolution of the breast cancer genome highlights the importance of using a recent sample for genomic profiling to guide clinical decision-making. Obtaining a metastatic tissue biopsy can be challenging, and analysis of circulating tumor DNA (ctDNA) from blood may provide a minimally invasive alternative. PATIENTS AND METHODS: Hybrid capture-based genomic profiling was carried out on ctDNA from 254 female patients with estrogen receptor-positive breast cancer. Peripheral blood samples were submitted by clinicians in the course of routine clinical care between May 2016 and March 2017. Sequencing of 62 genes was carried out to a median unique coverage depth of 7503×. Genomic alterations (GAs) in ctDNA were evaluated and compared with matched tissue samples and genomic datasets of tissue from breast cancer. RESULTS: At least 1 GA was reported in 78% of samples. Frequently altered genes were TP53 (38%), ESR1 (31%) and PIK3CA (31%). Temporally matched ctDNA and tissue samples were available for 14 patients; 89% of mutations detected in tissue were also detected in ctDNA. Diverse ESR1 GAs including mutation, rearrangement and amplification, were observed. Multiple concurrent ESR1 GAs were observed in 40% of ESR1-altered cases, suggesting polyclonal origin; ESR1 compound mutations were also observed in two cases. ESR1-altered cases harbored co-occurring GAs in PIK3CA (35%), FGFR1 (16%), ERBB2 (8%), BRCA1/2 (5%), and AKT1 (4%). CONCLUSIONS: GAs relevant to relapsed/metastatic breast cancer management were identified, including diverse ESR1 GAs. Genomic profiling of ctDNA demonstrated sensitive detection of mutations found in tissue. Detection of amplifications was associated with ctDNA fraction. Genomic profiling of ctDNA may provide a complementary and possibly alternative approach to tissue-based genomic testing for patients with estrogen receptor-positive metastatic breast cancer.

Toxicodynetics in nordiazepam and oxazepam overdoses.

OBJECTIVES: Toxicodynetics aims at defining the time-course of major clinical events in drug overdose. We report the toxicodynetics in mono-intoxications with oxazepam and nordiazepam. METHODS: Cases of oxazepam or nordiazepam overdoses collected at the Paris poison control centre from 1999 to 2014 on the basis of self-report. A particular attention was paid to eliminate the concomitant alcohol or psychotropic co-ingestions. The toxicodynetic parameters were assessed as previously described. Results are expressed using 10-90 percentiles. In adults, the dose was normalized (TI, toxic Index) by dividing the supposed ingested dose by the maximal recommended dose. RESULTS: Two hundred and fifty-one and 74 cases of oxazepam and nordiazepam poisonings were included, respectively. The Emax for oxazepam and nordiazepam were sleepiness or obtundation in 106 and 36 cases, respectively. Coma was used to qualify only one oxazepam overdose. The median delay in onset of the Emax was 1.5h (0.33-15) in nordiazepam and 4h (0.5-15) in oxazepam overdose. In both overdoses, the onset of Emax occurred on an "on-off" mode. In adults, the greatest TIs in nordiazepam and oxazepam overdoses were 45 and 26.7, respectively. The TI in the oxazepam-induced coma was 26.7, the largest dose. CONCLUSION: Data collected in PCC allow determining a number of toxicodynetic parameters. Toxicodynetics showed that nordiazepam is not a cause of coma even in large overdose while oxazepam causes coma only at a very high dose. Deep coma in nordiazepam overdose whatever the dose and deep coma in overdose with oxazepam involving TI less than 20 result from unrecognized drug-drug interaction.

Comprehensive genomic profiling of anal squamous cell carcinoma reveals distinct genomically defined classes.

BACKGROUND: Squamous cell cancers of the anal canal (ASCC) are increasing in frequency and lack effective therapies for advanced disease. Although an association with human papillomavirus (HPV) has been established, little is known about the molecular characterization of ASCC. A comprehensive genomic analysis of ASCC was undertaken to identify novel genomic alterations (GAs) that will inform therapeutic choices for patients with advanced disease. PATIENTS AND METHODS: Hybrid-capture-based next-generation sequencing of exons from 236 cancer-related genes and intronic regions from 19 genes commonly rearranged in cancer was performed on 70 patients with ASCC. HPV status was assessed by aligning tumor sequencing reads to HPV viral genomes. GAs were identified using an established algorithm and correlated with HPV status. RESULTS: Sixty-one samples (87%) were HPV-positive. A mean of 3.5 GAs per sample was identified. Recurrent alterations in phosphoinositol-3-kinase pathway (PI3K/AKT/mTOR) genes including amplifications and homozygous deletions were present in 63% of cases. Clinically relevant GAs in genes involved in DNA repair, chromatin remodeling, or receptor tyrosine kinase signaling were observed in 30% of cases. Loss-of-function mutations in TP53 and CDKN2A were significantly enhanced in HPV-negative cases (P < 0.0001). CONCLUSIONS: This is the first comprehensive genomic analysis of ASCC, and the results suggest new therapeutic approaches. Differing genomic profiles between HPV-associated and HPV-negative ASCC warrants further investigation and may require novel therapeutic and preventive strategies.

COMMUNITY CO-DESIGNED SCHISTOSOMIASIS CONTROL INTERVENTIONS FOR SCHOOL-AGED CHILDREN IN ZANZIBAR.

Top-down biomedical interventions to control schistosomiasis in sub-Saharan Africa have had limited success, primarily because they fail to engage with the social, political, economic and ecological contexts in which they are delivered. Despite the call to foster community engagement and to adapt interventions to local circumstances, programmes have rarely embraced such an approach. This article outlines a community co-designed process, based upon Human-Centered Design, to demonstrate how this approach works in practice. It is based on initial work undertaken by social science researchers, public health practitioners and community members from the Zanzibar Islands, Tanzania, between November 2011 and December 2013. During the process, 32 community members participated in a qualitative and quantitative data-driven workshop where they interpreted data on local infections from S. haematobium and co-designed interventions with the assistance of a facilitator trained in the social sciences. These interventions included the implementation of novel school-based education and training, the identification of relevant safe play activities and events at local schools, the installation of community-designed urinals for boys and girls and the installation of community-designed laundry-washing platforms to reduce exposure to cercariae-contaminated fresh water. It is suggested that the a community co-designed process, drawing from Human-Centered Design principles and techniques, enables the development of more sustainable and effective interventions for the control of schistosomiasis.

Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing.

BACKGROUND: To determine genomic alterations in head and neck squamous cell carcinoma (HNSCC) using formalin-fixed, paraffin-embedded (FFPE) tumors obtained through routine clinical practice, selected cancer-related genes were evaluated and compared with alterations seen in frozen tumors obtained through research studies. PATIENTS AND METHODS: DNA samples obtained from 252 FFPE HNSCC were analyzed using next-generation sequencing-based (NGS) clinical assay to determine sequence and copy number variations in 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. Human papillomavirus (HPV) status was determined by presence of the HPV DNA sequence in all samples and corroborated with high-risk HPV in situ hybridization (ISH) and p16 immunohistochemical (IHC) staining in a subset of tumors. Sequencing data from 399 frozen tumors in The Cancer Genome Atlas and University of Chicago public datasets were analyzed for comparison. RESULTS: Among 252 FFPE HNSCC, 84 (33%) were HPV positive and 168 (67%) were HPV negative by sequencing. A subset of 40 tumors with HPV ISH and p16 IHC results showed complete concordance with NGS-derived HPV status. The most common genes with genomic alterations were PIK3CA and PTEN in HPV-positive tumors and TP53 and CDKN2A/B in HPV-negative tumors. In the pathway analysis, the PI3K pathway in HPV-positive tumors and DNA repair-p53 and cell cycle pathways in HPV-negative tumors were frequently altered. The HPV-positive oropharynx and HPV-positive nasal cavity/paranasal sinus carcinoma shared similar mutational profiles. CONCLUSION: The genomic profile of FFPE HNSCC tumors obtained through routine clinical practice is comparable with frozen tumors studied in research setting, demonstrating the feasibility of comprehensive genomic profiling in a clinical setting. However, the clinical significance of these genomic alterations requires further investigation through application of these genomic profiles as integral biomarkers in clinical trials.

Decolonisation of MRSA and its effect on surgical site infections--a study in a tertiary care institute.

BACKGROUND: Two-thirds of surgical site infections (SSI) because of Staphylococcus aureus are caused by Methicillin resistant Staphylococcus aureus (MRSA). This study was done to assess the efficacy of topical 2% mupirocin with 2% chlorhexidine gluconate body wash in decolonizing MRSA and its impact in preventing SSI because of MRSA. The various risk factors associated with MRSA carriers and SSI were also studied because of paucity of data in the developing world. METHODS: We did a non-randomised interventional trial in 602 patients undergoing elective general surgical operations. All patients in case (297) group were screened for MRSA and those positive were decolonised with topical 2% mupirocin calcium ointment and daily baths with 2% chlorhexidine antiseptic solution for 5 days. Control (305) group patients underwent surgery without decolonisation. Postoperatively, all patients were followed up for SSI for 30 days. RESULTS: Prevalence of MRSA carriers was 7.5% with decolonisation rate of 95.2%. The SSI incidence was 21.3%. The significant risk factors for SSI were type of anaesthesia (p = 0.002), duration of surgery (p = 0.001) and preoperative hospital stay (p = 0.001). There was a significant association between MRSA carrier positivity at the time of surgery and SSI (p = 0.041). CONCLUSIONS: There was no reduction in rate of SSI or other nosocomial infections in patients undergoing elective general surgical operations following preoperative MRSA decolonisation with 2% mupirocin and 2% chlorhexidine gluconate in MRSA carriers. MRSA carrier status was a significant risk factor for SSI but not for other nosocomial infections.

Comparison of the Kato-Katz method and ether-concentration technique for the diagnosis of soil-transmitted helminth infections in the framework of a randomised controlled trial.

Soil-transmitted helminth infections are a major public health problem. An accurate diagnosis is important in order to identify individuals and communities in need of intervention, and for monitoring drug efficacy and potential emergence of resistance. We compared the accuracy of the Kato-Katz method and ether-concentration technique for the diagnosis of soil-transmitted helminth infections within a randomised controlled trial. Quadruplicate Kato-Katz thick smears (duplicate Kato-Katz from two stool samples each) were examined before (baseline) and 3 weeks after treatment (follow-up). Additionally, at baseline and follow-up, the first stool sample was subjected to an ether-concentration method. We determined the prevalence, sensitivity, negative predictive value, diagnostic agreement and cure rates for single and duplicate Kato-Katz thick smears from the first stool sample, quadruplicate Kato-Katz thick smears produced from two stool samples and single ether-concentration as compared to our 'gold' standard (i.e. quadruplicate Kato-Katz plus ether-concentration). Quadruplicate Kato-Katz revealed a higher sensitivity than single ether-concentration for Trichuris trichiura at baseline (94.3 % vs. 88.5 %, p = 0.002) and follow-up (93.8 % vs. 83.5 %, p < 0.001). In contrary, at follow-up, ether-concentration showed a higher sensitivity than quadruplicate Kato-Katz for Ascaris lumbricoides diagnosis (86.7 % vs. 46.7 %, p = 0.012). The ether-concentration method showed similar or slightly higher sensitivity than the Kato-Katz technique based on a single stool sample for all soil-transmitted helminth infections. The estimated cure rates were heavily dependent on the diagnostic technique and sampling effort. In conclusion, data on the prevalence of soil-transmitted helminth infections and the efficacy of anthelminthics are greatly influenced by the diagnostic method and sampling effort. The ether-concentration technique is a valuable alternative to the Kato-Katz method for helminth diagnosis.

Molecular characterization of high-level-cholera-toxin-producing El Tor variant Vibrio cholerae strains in the Zanzibar Archipelago of Tanzania.

Analysis of 1,180 diarrheal stool samples in Zanzibar detected 247 Vibrio cholerae O1, Ogawa strains in 2009. Phenotypic traits and PCR-based detection of rstR, rtxC, and tcpA alleles showed that they belonged to the El Tor biotype. Genetic analysis of ctxB of these strains revealed that they were classical type, and production of classical cholera toxin B (CTB) was confirmed by Western blotting. These strains produced more CT than the prototype El Tor and formed a separate cluster by pulsed-field gel electrophoresis (PFGE) analysis.

Comprehensive genomic profiling of epithelial ovarian cancer by next generation sequencing-based diagnostic assay reveals new routes to targeted therapies.

OBJECTIVE: Targeted next generation sequencing (NGS) was evaluated for its ability to identify unanticipated targetable genomic alterations (GA) for patients with relapsed ovarian epithelial carcinoma (OC). METHODS: DNA sequencing was performed for 3320 exons of 182 cancer-related genes and 37 introns of 14 genes frequently rearranged in cancer on indexed, adaptor ligated, hybridization-captured libraries using DNA isolated from FFPE sections from 48 histologically verified relapsed OC specimens. The original primary tumor was sequenced in 26 (54%) of the cases and recurrent/metastatic tumor site biopsies were sequenced in 22 (46%) of the cases. Actionability was defined as: GA that predict sensitivity or resistance to approved or standard therapies or are inclusion or exclusion criteria for specific experimental therapies in NCI registered clinical trials. RESULTS: There were 38 (80%) serous, 5 (10%) endometrioid, 3 (6%) clear cell, 1 mucinous (2%) and 1 (2%) undifferentiated carcinomas. 141 GA were identified with an average of 2.9 GA (range 0-8) per tumor, of which 67 were actionable for an average of 1.4 actionable GA per patient (range 0-5). 33/48 (69%) of OC patient samples harbored at least one actionable GA. Most common GA were TP53 (79%); MYC (25%); BRCA1/2 (23%); KRAS (16.6%) and NF1 (14.5%). One tumor featured an ERBB2 point mutation. One of 3 (33%) of clear cell tumors featured cMET amplification validated by both FISH and IHC. CONCLUSIONS: NGS assessment of therapy resistant OC identifies an unexpectedly high frequency of GA that could influence targeted therapy selection for the disease.