Treatment outcome of tubercular lymphadenopathy cases treated under dots: a five year follow up study

Background: Treatment of tubercular lymphadenopathy consists of at least 6 months of therapy with antitubercular drugs as DOTS in India. Some studies recommend that extension of therapy for some time may lead to lesser recurrence and relapse. This study was planned to assess the outcome of DOTS therapy in lymph node tuberculosis (TB) cases treated under RNTCP and to find out the prevalence of relapse in these patients in southern Rajasthan.Methods: This was a retrospective analysis of 275 cases of lymph node tuberculosis treated with DOTS under RNTCP. An immediate outcome of these cases was recorded and further traceable 81 patients were interviewed for long term outcome.Results: In our study population, treatment completion rate was 93.09%, defaulter rate was 4% and death reported in 3.7% (3/81) cases. We observed relapse rate of 9.1% after treatment completion. A total of 7.04% patients received extended treatment and none of them had relapsed during our follow up.Conclusions: Our study confirms that the efficacy of DOTS treatment is quite good in cases of tubercular lymphadenopathy but still requires review of programmatic strategy. An extension of antitubercular therapy is recommended because patients treated with DOTS had a little higher relapse rate in comparison to whom the treatment extended who had no recurrence and relapse

Caste and identity processes among British Sikhs in the Midlands

This article examines the role of caste in the lives and identities of a small sample of young Sikhs in the English Midlands, using social psychological theory. In many academic writings, there is an implicit representation of caste as a negative aspect of South Asian culture and religion, and of caste identification as a means of oppressing vulnerable outgroups. Twenty-three young Sikhs were interviewed, and the qualitative data were analysed using Identity Process Theory. The following themes are discussed: (i) Caste as a Dormant Social Category, (ii) Anchoring the Caste Ingroup to Positive Social Representations, and (iii) Caste as an Inherent or Constructed Aspect of Identity? It is argued that neither caste nor caste-based prejudice appear to be prominent in the lives and identities of our interviewees but that, because caste is an important symbolic aspect of identity which can acquire salient in particular contexts, some Sikhs may wish to maintain this identity though endogamy. What is understood as caste-based prejudice can be better understood in terms of the downward comparison principle in social psychology. The implications for caste legislation are discussed

Distinct Roles for Aryl Hydrocarbon Receptor Nuclear Translocator and Ah Receptor in Estrogen-Mediated Signaling in Human Cancer Cell Lines

The activated AHR/ARNT complex (AHRC) regulates the expression of target genes upon exposure to environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Importantly, evidence has shown that TCDD represses estrogen receptor (ER) target gene activation through the AHRC. Our data indicates that AHR and ARNT act independently from each other at non-dioxin response element sites. Therefore, we sought to determine the specific functions of AHR and ARNT in estrogen-dependent signaling in human MCF7 breast cancer and human ECC-1 endometrial carcinoma cells. Knockdown of AHR with siRNA abrogates dioxin-inducible repression of estrogen-dependent gene transcription. Intriguingly, knockdown of ARNT does not effect TCDD-mediated repression of estrogen-regulated transcription, suggesting that AHR represses ER function independently of ARNT. This theory is supported by the ability of the selective AHR modulator 3′,4′-dimethoxy-α-naphthoflavone (DiMNF) to repress estrogen-inducible transcription. Furthermore, basal and estrogen-activated transcription of the genes encoding cathepsin-D and pS2 are down-regulated in MCF7 cells but up-regulated in ECC-1 cells in response to loss of ARNT. These responses are mirrored at the protein level with cathepsin-D. Furthermore, knock-down of ARNT led to opposite but corresponding changes in estrogen-stimulated proliferation in both MCF7 and ECC-1 cells. We have obtained experimental evidence demonstrating a dioxin-dependent repressor function for AHR and a dioxin-independent co-activator/co-repressor function for ARNT in estrogen signalling. These results provide us with further insight into the mechanisms of transcription factor crosstalk and putative therapeutic targets in estrogen-positive cancers

Sparsity and Incoherence in Compressive Sampling

We consider the problem of reconstructing a sparse signal $x^0\in\R^n$ from a limited number of linear measurements. Given $m$ randomly selected samples of $U x^0$, where $U$ is an orthonormal matrix, we show that $\ell_1$ minimization recovers $x^0$ exactly when the number of measurements exceeds $$m\geq \mathrm{Const}\cdot\mu^2(U)\cdot S\cdot\log n,$$ where $S$ is the number of nonzero components in $x^0$, and $\mu$ is the largest entry in $U$ properly normalized: $\mu(U) = \sqrt{n} \cdot \max_{k,j} |U_{k,j}|$. The smaller $\mu$, the fewer samples needed. The result holds for ``most'' sparse signals $x^0$ supported on a fixed (but arbitrary) set $T$. Given $T$, if the sign of $x^0$ for each nonzero entry on $T$ and the observed values of $Ux^0$ are drawn at random, the signal is recovered with overwhelming probability. Moreover, there is a sense in which this is nearly optimal since any method succeeding with the same probability would require just about this many samples

Development and user-testing of a digital patient decision aid to facilitate shared decision-making for people with stable angina

Background Research shows that people with stable angina need decision support when considering elective treatments. Initial treatment is with medicines but patients may gain further benefit with invasive percutaneous coronary intervention (PCI). Choosing between these treatments can be challenging for patients because both confer similar benefits but have different risks. Patient decision aids (PtDAs) are evidence-based interventions that support shared decision-making (SDM) when making healthcare decisions. This study aimed to develop and user-test a digital patient decision aid (CONNECT) to facilitate SDM for people with stable angina considering invasive treatment with elective PCI. Methods A multi-phase study was conducted to develop and test CONNECT (COroNary aNgioplasty dECision Tool) using approaches recommended by the International Patient Decision Aid Standards Collaboration: (i) Steering Group assembled, (ii) review of clinical guidance, (iii) co-design workshops with patients and cardiology health professionals, (iv) first prototype developed and ‘alpha’ tested (semi-structured cognitive interviews and 12-item acceptability questionnaire) with patients, cardiologists and cardiac nurses, recruited from two hospitals in Northern England, and (v) final PtDA refined following iterative user-feedback. Quantitative data were analysed descriptively and qualitative data from the interviews analysed using deductive content analysis. Results CONNECT was developed and user-tested with 34 patients and 29 cardiology health professionals. Findings showed that CONNECT was generally acceptable, usable, comprehensible, and desirable. Participants suggested that CONNECT had the potential to improve care quality by personalising consultations and facilitating SDM and informed consent. Patient safety may be improved as CONNECT includes questions about symptom burden which can identify asymptomatic patients unlikely to benefit from PCI, as well as those who may need to be fast tracked because of worsening symptoms. Conclusions CONNECT is the first digital PtDA for people with stable angina considering elective PCI, developed in the UK using recommended processes and fulfilling international quality criteria. CONNECT shows promise as an approach to facilitate SDM and should be evaluated in a clinical trial. Further work is required to standardise the provision of probabilistic risk information for people considering elective PCI and to understand how CONNECT can be accessible to underserved communities

An Experimental Study of Effects of Step Roughness in Skimming Flows on Stepped Chutes

On a spillway chute, a stepped design increases the rate of energy dissipation on the chute itself and reduces the size of a downstream energy dissipator. Up to date, the effects of step roughness on the flow properties remain unknown despite the practical relevance to damaged concrete steps, rock chutes and gabions weirs. New measurements were conducted in a large-size laboratory facility with two step conditions (smooth and rough) and three types of step roughness. Detailed air-water flow properties were measured systematically for several flow rates. The results showed faster flow motion on rough step chutes. Although the finding is counter-intuitive, it is linked with the location of the inception point of free-surface aeration being located further downstream than for a smooth stepped chute for an identical flow rate. In the aerated flow region, the velocities on rough-step chutes were larger than those of smooth chute flows for a given flow rate and dimensionless location from the inception point of free-surface aeration both at step edges and between step edges. The results suggest that design guidelines for smooth (concrete) stepped spillway may not be suitable to rough stepped chutes including gabion stepped weirs, and older stepped chutes with damaged steps

The feasibility of the PAM intervention to support treatment-adherence in people with hypertension in primary care: a randomised clinical controlled trial.

The PAM intervention is a behavioural intervention to support adherence to anti-hypertensive medications and therefore to lower blood pressure. This feasibility trial recruited 101 nonadherent patients (54% male, mean age 65.8 years) with hypertension and high blood pressure from nine general practices in the UK. The trial had 15.5% uptake and 7.9% attrition rate. Patients were randomly allocated to two groups: the intervention group (n = 61) received the PAM intervention as an adjunct to usual care; the control group (n = 40) received usual care only. At 3 months, biochemically validated medication adherence was improved by 20% (95% CI 3-36%) in the intervention than control, and systolic blood pressure was reduced by 9.16 mmHg (95% CI 5.69-12.64) in intervention than control. Improvements in medication adherence and reductions in blood pressure suggested potential intervention effectiveness. For a subsample of patients, improvements in medication adherence and reductions in full lipid profile (cholesterol 1.39 mmol/mol 95% CI 0.64-1.40) and in glycated haemoglobin (3.08 mmol/mol, 95% CI 0.42-5.73) favoured the intervention. A larger trial will obtain rigorous evidence about the potential clinical effectiveness and cost-effectiveness of the intervention.Trial registration Trial date of first registration 28/01/2019. ISRCTN74504989. https://doi.org/10.1186/ISRCTN74504989

Positron emission tomographic imaging of tumor cell death using zirconium-89-labeled APOMAB(R) following cisplatin chemotherapy in lung and ovarian cancer xenograft models

Published online 06 July 2021Purpose Early detection of tumor treatment responses represents an unmet clinical need with no approved noninvasive methods. DAB4, or its chimeric derivative, chDAB4 (APOMAB®) is an antibody that targets the Lupus associated antigen (La/SSB). La/SSB is over-expressed in malignancy and selectively targeted by chDAB4 in cancer cells dying from DNA-damaging treatment. Therefore, chDAB4 is a unique diagnostic tool that detects dead cancer cells and thus could distinguish between treatment responsive and nonresponsive patients. Procedures In clinically relevant tumor models, mice bearing subcutaneous xenografts of human ovarian or lung cancer cell lines or intraperitoneal ovarian cancer xenografts were untreated or given chemotherapy followed 24h later by chDAB4 radiolabeled with [⁸⁹Zr]ZrIV. Tumor responses were monitored using bioluminescence imaging and caliper measurements. [⁸⁹Zr]Zr-chDAB4 uptake in tumor and normal tissues was measured using an Albira SI Positron-Emission Tomography (PET) imager and its biodistribution was measured using a Hidex gamma-counter. Results Tumor uptake of [⁸⁹Zr]Zr-chDAB4 was detected in untreated mice, and uptake significantly increased in both human lung and ovarian tumors after chemotherapy, but not in normal tissues. Conclusion Given that tumors, rather than normal tissues, were targeted after chemotherapy, these results support the clinical development of chDAB4 as a radiodiagnostic imaging agent and as a potential predictive marker of treatment response.Vasilios Liapis, William Tieu, Nicole L. Wittwer, Tessa Gargett, Andreas Evdokiou, Prab Takhar, Stacey E. Rudd, Paul S. Donnelly, Michael P. Brown, Alexander H. Staudache

Co-design of digital learning resources for care workers: reflections on the neurocare knowhow project

Neurocare Knowhow is an online learning platform for care workers who support people with neurological conditions. Care workers often do not receive specialist training around neurological conditions and can experience anxiety and apprehension about caring for this group. Neurocare Knowhow aims to increase care workers’ knowledge and confidence. Featuring flexible and personalisable digital features, in combination with documentary video and audio, it offers an alternative to traditional e-learning, moving away from longform didactic courses to flexible on-the-go learning. This co-design project worked closely with people with neurological conditions, their families, care workers and care organisation managers to validate the need and develop a proof of concept pilot. Co-design activity took place across multiple workshops in person and online. These gathered detailed insights into preferred features that support engaging online learning. The platform offers learning across diverse neurological conditions as a whole, with a focus on shared symptoms and challenges encountered by people with neurological conditions. Ongoing development to scale the pilot up to meet an anticipated national audience includes a focus on artificial intelligence to support searches at a moment of need and a range of personalisable features for individual and team learning