134 research outputs found

    The Response of Karachi Stock Exchange to Nuclear Detonation

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    Stock markets are highly reactive to internal and external developments. News of major events take no time to impact, the Stock Exchange that quite often serves as a barometer of the good and bad for the market. The importance of particular events and their effect on the stock market has been a subject of study in financial literature. Such studies attempt to assess the extent to which stock markets’ performance stray’s from the normal around the time of the occurrence of subject events. The stock market crash in the USA of October 1987 and related crash in the Far East later in January 1998 led to several studies of the event. On October 14, 1987, the US stock market began the steepest decline of its history, culminating in the crash of October 19, when the Dow Jones Industrial Average fell 508 points (22.6 percent). Certain aspects of the event of Black Monday as it is called emphasised the need for research to explore what fundamental economic factors triggered the large decline and the institutional and structural factors that were inherent in the trading strategies of investors. Michell and Netter (1989) have presented evidence that a tax bill containing anti takeover provision proposed by the U.S. House Ways and Means Committee of Oct. 13, 1987 was the economic event that triggered the October 19 crash. Other events and economic conditions during October 14–16 have been cited in the literature including higher than expected trade deficits, rising interest rate and increased worries about the government deficit and fear of inflation by many studies. Certain trading strategies such as index arbitrage and portfolio insurance has been cited by the Report of Presidential Task Force (1988). Roll (1988) has argued the crash did not begin in US since many other world markets experienced a severe decline on October 19 before US markets opened.

    The Response of Karachi Stock Exchange to Nuclear Detonation

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    Stock markets are highly reactive to internal and external developments. News of major events take no time to impact, the Stock Exchange that quite often serves as a barometer of the good and bad for the market. The importance of particular events and their effect on the stock market has been a subject of study in financial literature. Such studies attempt to assess the extent to which stock markets’ performance stray’s from the normal around the time of the occurrence of subject events. The stock market crash in the USA of October 1987 and related crash in the Far East later in January 1998 led to several studies of the event

    NEOADJUVANT WEEKLY NAB-PACLITAXEL PLUS CARBOPLATIN FOLLOWED BY DOXORUBICIN PLUS CYCLOPHOSPHAMIDE WITH BEVACIZUMAB ADDED CONCURRENTLY TO CHEMOTHERAPY FOR OPERABLE TRIPLE-NEGATIVE INVASIVE BREAST CANCER

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    Purpose: This phase II neoadjuvant study investigated whether nab paclitaxel, carboplatin and bevacizumab given before neoadjuvant doxorubicin/cyclophosphamide (AC) produced higher pathologic complete response (pCR) rates in triple- negative breast cancer (TNBC) compared with historical results achieved with standard anthracycline/taxane regimens. Patients and Methods: Eligible patients with operable TNBC ≥2 cm received four cycles of carboplatin (area under the curve 6, day 1) plus nab-paclitaxel (100 mg/m2, days 1, 8 and 15) every 28 days, followed by four 14-day cycles of AC neoadjuvantly, with bevacizumab 10 mg/kg every 14 days for the rst 6 cycles of neoadjuvant chemotherapy, resuming postoperatively to complete 1 year of antibody treatment. In breast pCR and pCR (breast + nodes) were primary and secondary endpoints, respectively. Results: Due to slow accrual, the study was closed after enrollment of 42 of 60 planned patients. Of the 38 patients who underwent surgery (ef cacy population), 22 (58%) achieved an in-breast pCR and 19 (50%) achieved a pCR (breast + nodes). Neutropenia was the most common Grade 3/4 adverse event (57% Grade 3 and 31% Grade 4), but only 1 patient required hospitalisation and IV antibiotics for neutropenic fever. Other Grade 3/4 events included anaemia (24%), thrombocytopenia (29%) and peripheral neuropathy (Grade 3, 5%). Conclusion: Our results demonstrate a substantially higher pCR rate, both in-breast and breast + nodes, with the combination of nab paclitaxel plus carboplatin followed by AC, with concurrent bevacizumab, versus historic pCR rates with anthracycline-taxane regimens alone, supporting further investigation of this regimen, preferably in molecularly driven subsets, for the neoadjuvant treatment of patients with TNBC. Key words: Bevacizumab, breast cancer, carboplatin, nab-paclitaxel, neoadjuvant, triple-negative

    Atypical right diaphragmatic hernia (hernia of Morgagni), spigelian hernia and epigastric hernia in a patient with Williams syndrome: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Williams syndrome is rare genetic disorder resulting in neurodevelopmental problems. Hernias of the foramen of Morgagni are rare diaphragmatic hernias and they mostly present on the right side, in the anterior mediastinum. They are usually asymptomatic and are difficult to diagnose, especially in patients with learning disabilities.</p> <p>Case presentation</p> <p>This 49-year-old woman with Williams syndrome, cognitive impairment and aortic stenosis presented to physicians with right-sided chest pain. She had previously undergone repair of her right spigelian and epigastric hernia. Her abdominal examination was unremarkable. Chest X-ray suggested right-sided diaphragmatic hernia and pleural effusion for which she received treatment. The computed tomography scan showed a diaphragmatic hernia with some collapse/consolidation of the adjacent lung. Furthermore, the patient had aortic stenosis and was high risk for anaesthesia (ASA grade 3). She underwent successful laparoscopic repair of her congenital diaphragmatic hernia leading to a quick and uneventful postoperative recovery.</p> <p>Conclusion</p> <p>These multiple hernias suggest that patients with Williams syndrome may have some connective tissue disorder which makes them prone to develop hernias especially associated with those parts of the body which may have intracavity pressure variations like the abdomen. Diaphragmatic hernia may be the cause of chest pain in these patients. A computed tomography scan helps in early diagnosis, and laparoscopic repair helps in prevention of further complications, and leads to quick recovery especially in patients with learning disabilities. In the presence of significant comorbidities, a less invasive operative procedure with quick recovery becomes advisable.</p

    Is there a role for natural desiccated thyroid in the treatment of levothyroxine unresponsive hypothyroidism? Results from a consecutive case series

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    From Wiley via Jisc Publications RouterHistory: received 2021-08-10, rev-recd 2021-09-19, accepted 2021-10-06, pub-electronic 2021-11-20Article version: VoRPublication status: PublishedAbstract: Introduction: Some levothyroxine unresponsive individuals with hypothyroidism are prescribed a natural desiccated thyroid (NDT) preparation such as Armour Thyroid ® or ERFA Thyroid ® . These contain a mixture of levothyroxine and liothyronine in a fixed ratio. We evaluated the response to NDT in individuals at a single endocrine centre in terms of how the change from levothyroxine to NDT impacted on their lives in relation to quality of life (QOL) and thyroid symptoms. Methods: The ThyPRO39 (thyroid symptomatology) and EQ‐5D‐5L‐related QoL/EQ5D5L (generic QOL) questionnaires were administered to 31 consecutive patients who had been initiated on NDT, before initiating treatment/6 months later. Results: There were 28 women and 3 men. The dose range of NDT was 60‐180 mg daily. Age range was 26‐77 years with length of time since diagnosis with hypothyroidism ranging from 2 to 40 years. One person discontinued the NDT because of lack of response; two because of cardiac symptoms. EQ‐5D‐5L utility increased from a mean (SD) of 0.214 (0.338) at baseline, to 0.606 (0.248) after 6 months; corresponding to a difference of 0.392 (95% CI 0.241‐0.542), t = 6.82, P < .001. EQ‐VAS scores increased from 33.4 (17.2) to 71.1 (17.5), a difference of 37.7 (95% CI 25.2‐50.2), t = −4.9, P < .001. ThyPRO scores showed consistent fall across all domains with the composite QoL‐impact Score improving from 68.3 (95% CI 60.9‐75.7) to 25.2 (95% CI 18.7‐31.7), a difference of 43.1 (95% CI 33‐53.2) (t = 5.6, P < .001). Conclusion: Significant symptomatic benefit and improvement in QOL was experienced by people with a history of levothyroxine unresponsive hypothyroidism treated with NDT, suggesting the need for further evaluation of NDT in this context

    Colorization and Automated Segmentation of Human T2 MR Brain Images for Characterization of Soft Tissues

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    Characterization of tissues like brain by using magnetic resonance (MR) images and colorization of the gray scale image has been reported in the literature, along with the advantages and drawbacks. Here, we present two independent methods; (i) a novel colorization method to underscore the variability in brain MR images, indicative of the underlying physical density of bio tissue, (ii) a segmentation method (both hard and soft segmentation) to characterize gray brain MR images. The segmented images are then transformed into color using the above-mentioned colorization method, yielding promising results for manual tracing. Our color transformation incorporates the voxel classification by matching the luminance of voxels of the source MR image and provided color image by measuring the distance between them. The segmentation method is based on single-phase clustering for 2D and 3D image segmentation with a new auto centroid selection method, which divides the image into three distinct regions (gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) using prior anatomical knowledge). Results have been successfully validated on human T2-weighted (T2) brain MR images. The proposed method can be potentially applied to gray-scale images from other imaging modalities, in bringing out additional diagnostic tissue information contained in the colorized image processing approach as described

    Force Generation upon T Cell Receptor Engagement

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    T cells are major players of adaptive immune response in mammals. Recognition of an antigenic peptide in association with the major histocompatibility complex at the surface of an antigen presenting cell (APC) is a specific and sensitive process whose mechanism is not fully understood. The potential contribution of mechanical forces in the T cell activation process is increasingly debated, although these forces are scarcely defined and hold only limited experimental evidence. In this work, we have implemented a biomembrane force probe (BFP) setup and a model APC to explore the nature and the characteristics of the mechanical forces potentially generated upon engagement of the T cell receptor (TCR) and/or lymphocyte function-associated antigen-1 (LFA-1). We show that upon contact with a model APC coated with antibodies towards TCR-CD3, after a short latency, the T cell developed a timed sequence of pushing and pulling forces against its target. These processes were defined by their initial constant growth velocity and loading rate (force increase per unit of time). LFA-1 engagement together with TCR-CD3 reduced the growing speed during the pushing phase without triggering the same mechanical behavior when engaged alone. Intracellular Ca2+ concentration ([Ca2+]i) was monitored simultaneously to verify the cell commitment in the activation process. [Ca2+]i increased a few tens of seconds after the beginning of the pushing phase although no strong correlation appeared between the two events. The pushing phase was driven by actin polymerization. Tuning the BFP mechanical properties, we could show that the loading rate during the pulling phase increased with the target stiffness. This indicated that a mechanosensing mechanism is implemented in the early steps of the activation process. We provide here the first quantified description of force generation sequence upon local bidimensional engagement of TCR-CD3 and discuss its potential role in a T cell mechanically-regulated activation process

    Concurrent Proinflammatory and Apoptotic Activity of a Helicobacter pylori Protein (HP986) Points to Its Role in Chronic Persistence

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    Helicobacter pylori induces cytokine mediated changes in gastroduodenal pathophysiology, wherein, the activated macrophages at the sub-mucosal space play a central role in mounting innate immune response against the antigens. The bacterium gains niche through persistent inflammation and local immune-suppression causing peptic ulcer disease or chronic gastritis; the latter being a significant risk factor for the development of gastric adenocarcinoma. What favors persistence of H. pylori in the gastric niches is not clearly understood. We report detailed characterization of a functionally unknown gene (HP986), which was detected in patient isolates associated with peptic ulcer and gastric carcinoma. Expression and purification of recombinant HP986 (rHP986) revealed a novel, ∼29 kDa protein in biologically active form which associates with significant levels of humoral immune responses in diseased individuals (p<0.001). Also, it induced significant levels of TNF-α and Interleukin-8 in cultured human macrophages concurrent to the translocation of nuclear transcription factor-κB (NF-κB). Further, the rHP986 induced apoptosis of cultured macrophages through a Fas mediated pathway. Dissection of the underlying signaling mechanism revealed that rHP986 induces both TNFR1 and Fas expression to lead to apoptosis. We further demonstrated interaction of HP986 with TNFR1 through computational and experimental approaches. Independent proinflammatory and apoptotic responses triggered by rHP986 as shown in this study point to its role, possibly as a survival strategy to gain niche through inflammation and to counter the activated macrophages to avoid clearance
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