Design, fabrication and performance evaluation of a 22-channel direct reading atomic emission spectrometer using inductively coupled plasma as a source of excitation

The indigenous design, fabrication and performance evaluation of a polychromator, using inductively coupled plasma (ICP) as a source of excitation, are described. A concave holographic grating is used as the dispersing element and a Paschen-Runge mount is chosen to focus the spectra over a wide range along the Rowland circle. Twenty-two exit slits, mounted along the circle, precisely correspond to the wavelengths used for determination of up to twenty elements present in the plasma. Radiations emerging from the exit slits are detected by photomultiplier tubes placed behind them. The photomultiplier signal is recorded by an electronic system consisting of an integrator and a PC-based data acquisition system. The performance of the spectrometer has been evaluated with an ICP excitation source. Synthetic standards in deionized water containing a mixture of twenty impurities have been analysed. Typical determination limits observed for elements range from sub-ppm to ppm levels. All the elements present as impurities can be detected simultaneously. It is also observed that each element has a different emitting region in the ICP flame for which the maximum signal to the background is obtained. The determination limits obtained corresponding to these zones are the lowest. A study of the sensitive emitting zones for several elements has been carried out and the results are demonstrated by photographs of the ICP flame. The study will help in achieving the minimum value of determination limit for an impurity element

Validation of the AASLD recommendations for Classification of Oesophageal Varices in Clinical Practice

Background & Aims The American Association for the Study of Liver Diseases recommends the use of a 2‐grade classification system (small and large) to describe the size of oesophageal varices (OV). Data on observer agreement (OA) on this system are currently lacking. We aimed to evaluate this classification and compare it to the widely used 3‐grade classification (grade 1 ‘small’, grade 2 ‘medium’, grade 3 ‘large’) among operators of variable experience. Methods High‐definition video recordings of 100 patients with cirrhosis were prospectively collected using standardised criteria. Nine observers of variable experience performed independent evaluations of the videos in random order. OV were scored using both systems. All assessments were repeated a year later by the same observers to assess intra‐observer agreement. Results Interobserver agreement (all observers) using the 2‐grade and the 3‐grade system was k = 0.71 (95% CI: 0.64‐0.78) and k = 0.73 (95% CI: 0.66‐0.79) respectively. When using the 2‐grade system, intra‐observer agreement between hepatologists (n = 3), luminal gastroenterologists (n = 3) and trainee gastroenterologists (n = 3) was k = 0.89 (95% CI: 0.86‐0.91), k = 0.72 (95% CI: 0.67‐0.77), and k = 0.74 (95% CI: 0.67‐0.8) respectively. With the 3‐grade system; intra‐observer agreement between the same three subgroups were k = 0.9 (95% CI: 0.87‐0.92), k = 0.73 (95% CI: 0.68‐0.78), k = 0.77 (95% CI: 0.71‐0.82) respectively. Conclusions There was no difference in OA between the 2‐grade and 3‐grade classification systems. Hepatologists had significantly higher levels of consistency in grading OV. This may have implications to create alternative training models for residents and fellows in the recognition and grading of OV

Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model

BACKGROUND: Both cell-associated and cell-free HIV virions are present in semen and cervical secretions of HIV-infected individuals. Thus, topical microbicides may need to inactivate both cell-associated and cell-free HIV to prevent sexual transmission of HIV/AIDS. To determine if the mild acidity of the healthy vagina and acid buffering microbicides would prevent transmission by HIV-infected leukocytes, we measured the effect of pH on leukocyte motility, viability and intracellular pH and tested the ability of an acidic buffering microbicide (BufferGel(®)) to prevent the transmission of cell-associated HIV in a HuPBL-SCID mouse model. METHODS: Human lymphocyte, monocyte, and macrophage motilities were measured as a function of time and pH using various acidifying agents. Lymphocyte and macrophage motilities were measured using video microscopy. Monocyte motility was measured using video microscopy and chemotactic chambers. Peripheral blood mononuclear cell (PBMC) viability and intracellular pH were determined as a function of time and pH using fluorescent dyes. HuPBL-SCID mice were pretreated with BufferGel, saline, or a control gel and challenged with HIV-1-infected human PBMCs. RESULTS: Progressive motility was completely abolished in all cell types between pH 5.5 and 6.0. Concomitantly, at and below pH 5.5, the intracellular pH of PBMCs dropped precipitously to match the extracellular medium and did not recover. After acidification with hydrochloric acid to pH 4.5 for 60 min, although completely immotile, 58% of PBMCs excluded ethidium homodimer-1 (dead-cell dye). In contrast, when acidified to this pH with BufferGel, a microbicide designed to maintain vaginal acidity in the presence of semen, only 4% excluded dye at 10 min and none excluded dye after 30 min. BufferGel significantly reduced transmission of HIV-1 in HuPBL-SCID mice (1 of 12 infected) compared to saline (12 of 12 infected) and a control gel (5 of 7 infected). CONCLUSION: These results suggest that physiologic or microbicide-induced acid immobilization and killing of infected white blood cells may be effective in preventing sexual transmission of cell-associated HIV

No evidence for association of ataxia-telangiectasia mutated gene T2119C and C3161G amino acid substitution variants with risk of breast cancer

BACKGROUND: There is evidence that certain mutations in the double-strand break repair pathway ataxia-telangiectasia mutated gene act in a dominant-negative manner to increase the risk of breast cancer. There are also some reports to suggest that the amino acid substitution variants T2119C Ser707Pro and C3161G Pro1054Arg may be associated with breast cancer risk. We investigate the breast cancer risk associated with these two nonconservative amino acid substitution variants using a large Australian population-based case–control study. METHODS: The polymorphisms were genotyped in more than 1300 cases and 600 controls using 5' exonuclease assays. Case–control analyses and genotype distributions were compared by logistic regression. RESULTS: The 2119C variant was rare, occurring at frequencies of 1.4 and 1.3% in cases and controls, respectively (P = 0.8). There was no difference in genotype distribution between cases and controls (P = 0.8), and the TC genotype was not associated with increased risk of breast cancer (adjusted odds ratio = 1.08, 95% confidence interval = 0.59–1.97, P = 0.8). Similarly, the 3161G variant was no more common in cases than in controls (2.9% versus 2.2%, P = 0.2), there was no difference in genotype distribution between cases and controls (P = 0.1), and the CG genotype was not associated with an increased risk of breast cancer (adjusted odds ratio = 1.30, 95% confidence interval = 0.85–1.98, P = 0.2). This lack of evidence for an association persisted within groups defined by the family history of breast cancer or by age. CONCLUSION: The 2119C and 3161G amino acid substitution variants are not associated with moderate or high risks of breast cancer in Australian women

Microanatomy of Adult Zebrafish Extraocular Muscles

Binocular vision requires intricate control of eye movement to align overlapping visual fields for fusion in the visual cortex, and each eye is controlled by 6 extraocular muscles (EOMs). Disorders of EOMs are an important cause of symptomatic vision loss. Importantly, EOMs represent specialized skeletal muscles with distinct gene expression profile and susceptibility to neuromuscular disorders. We aim to investigate and describe the anatomy of adult zebrafish extraocular muscles (EOMs) to enable comparison with human EOM anatomy and facilitate the use of zebrafish as a model for EOM research. Using differential interference contrast (DIC), epifluorescence microscopy, and precise sectioning techniques, we evaluate the anatomy of zebrafish EOM origin, muscle course, and insertion on the eye. Immunofluorescence is used to identify components of tendons, basement membrane and neuromuscular junctions (NMJs), and to analyze myofiber characteristics. We find that adult zebrafish EOM insertions on the globe parallel the organization of human EOMs, including the close proximity of specific EOM insertions to one another. However, analysis of EOM origins reveals important differences between human and zebrafish, such as the common rostral origin of both oblique muscles and the caudal origin of the lateral rectus muscles. Thrombospondin 4 marks the EOM tendons in regions that are highly innervated, and laminin marks the basement membrane, enabling evaluation of myofiber size and distribution. The NMJs appear to include both en plaque and en grappe synapses, while NMJ density is much higher in EOMs than in somatic muscles. In conclusion, zebrafish and human EOM anatomy are generally homologous, supporting the use of zebrafish for studying EOM biology. However, anatomic differences exist, revealing divergent evolutionary pressures

How managers can build trust in strategic alliances: a meta-analysis on the central trust-building mechanisms

Trust is an important driver of superior alliance performance. Alliance managers are influential in this regard because trust requires active involvement, commitment and the dedicated support of the key actors involved in the strategic alliance. Despite the importance of trust for explaining alliance performance, little effort has been made to systematically investigate the mechanisms that managers can use to purposefully create trust in strategic alliances. We use Parkhe’s (1998b) theoretical framework to derive nine hypotheses that distinguish between process-based, characteristic-based and institutional-based trust-building mechanisms. Our meta-analysis of 64 empirical studies shows that trust is strongly related to alliance performance. Process-based mechanisms are more important for building trust than characteristic- and institutional-based mechanisms. The effects of prior ties and asset specificity are not as strong as expected and the impact of safeguards on trust is not well understood. Overall, theoretical trust research has outpaced empirical research by far and promising opportunities for future empirical research exist

Interaction of hnRNPA1/A2 and DAZAP1 with an Alu-Derived Intronic Splicing Enhancer Regulates ATM Aberrant Splicing

We have previously identified an Alu-derived Intronic Splicing enhancer (ISE) in the Ataxia Teleangectasia Mutated gene (ATM) that facilitates intron pre-mRNA processing and leads to the inclusion of a cryptic exon in the final mRNA transcript. By using an RNA pull-down assay, we show here that hnRNPA1/A2, HuR and DAZAP1 splicing factors and DHX36 RNA helicase bind to the ISE. By functional studies (overexpression and siRNA experiments), we demonstrate that hnRNPA1 and DAZAP1 are indeed involved in ISE-dependent ATM cryptic exon activation, with hnRNPA1 acting negatively and DAZAP1 positively on splicing selection. On the contrary, HuR and DHX36 have no effect on ATM splicing pattern. These data suggest that splicing factors with both negative and positive effect can assemble on the intronic Alu repeats and regulate pre-mRNA splicing

Menstrual hygiene management among women and adolescent girls in the aftermath of the earthquake in Nepal.

BACKGROUND: Menstrual hygiene management (MHM) is an essential aspect of hygiene for women and adolescent girls between menarche and menopause. Despite being an important issue concerning women and girls in the menstruating age group MHM is often overlooked in post-disaster responses. Further, there is limited evidence of menstrual hygiene management in humanitarian settings. This study aims to describe the experiences and perceptions of women and adolescent girls on menstrual hygiene management in post-earthquake Nepal. METHODS: A mixed methods study was carried out among the earthquake affected women and adolescent girls in three villages of Sindhupalchowk district of Nepal. Data was collected using a semi-structured questionnaire that captured experiences and perceptions of respondents on menstrual hygiene management in the aftermath of the Nepal earthquake. Quantitative data were triangulated with in-depth interview regarding respondent's personal experiences of menstrual hygiene management. RESULTS: Menstrual hygiene was rated as the sixth highest overall need and perceived as an immediate need by 18.8% of the respondents. There were 42.8% women & girls who menstruated within first week of the earthquake. Reusable sanitary cloth were used by about 66.7% of the respondents before the earthquake and remained a popular method (76.1%) post-earthquake. None of the respondents reported receiving menstrual adsorbents as relief materials in the first month following the earthquake. Disposable pads (77.8%) were preferred by respondents as they were perceived to be clean and convenient to use. Most respondents (73.5%) felt that reusable sanitary pads were a sustainable choice. Women who were in the age group of 15-34 years (OR = 3.14; CI = (1.07-9.20), did not go to school (OR = 9.68; CI = 2.16-43.33), married (OR = 2.99; CI = 1.22-7.31) and previously used reusable sanitary cloth (OR = 5.82; CI = 2.33-14.55) were more likely to use the reusable sanitary cloth. CONCLUSIONS: In the immediate aftermath of the earthquake, women and girls completely depended on the use of locally available resources as adsorbents during menstruation. Immediate relief activities by humanitarian agencies, lacked MHM activities. Understanding the previous practice and using local resources, the reusable sanitary cloth is a way to address the menstrual hygiene needs in the post-disaster situations in Nepal

The Comparative Oncology Trials Consortium: Using Spontaneously Occurring Cancers in Dogs to Inform the Cancer Drug Development Pathway

Chand Khanna and colleagues describe the work of the Comparative Oncology Trials Consortium (COTC), which provides infrastructure and resources to integrate naturally occurring dog cancer models into the development of new human cancer drugs, devices, and imaging techniques

RNAi-mediated COPS3 gene silencing inhibits metastasis of osteogenic sarcoma cells

Metastatic disease is the primary cause of mortality among patients with osteogenic sarcoma (OGS). In this study, we aimed to identify the relationship of COPS3 gene expression to metastasis. Immunohistochemical staining for COPS3 was performed on 65 OGS samples (37 without and 28 with metastatic disease); 18.9% (7/37) of specimens from patients with no metastasis and 57.1% (16/28) of specimens from patients with metastasis showed intense staining of COPS3. Comparison of COPS3 expression between a poorly metastatic osteosarcoma cell line (SAOS-2) and highly metastatic osteosarcoma cell line (HOS) showed stronger expression of COPS3 in HOS cells. Inhibiting COPS3 function by siRNA resulted in reduced proliferation and migration of HOS cells. Inhibition of COPS3 gene downregulated expression of the MAPK signaling pathway, which has an important role in metastasis of OGS. Our results suggested that overexpression of the COPS3 gene might have important roles in metastasis of osteosarcoma cells