Educational needs of patients, families, and healthcare professionals to support the patient journey in haemophilia gene therapy in the UK

With the first gene therapies for haemophilia approved by the European Commission, the US Food and Drug Administration, and the Medicines and Healthcare products Regulatory Agency, it is important to consider the remaining unmet needs and challenges that may arise throughout patients’ treatment journeys. We discuss existing unmet needs and important considerations prior to, during, and following haemophilia gene therapy treatment in the UK, and propose potential next steps. Key areas for attention are education, psychological support, and guidance on implementation. Strategies are urgently required to fulfil these needs. An immediate priority for information providers should be comprehensive education for people with haemophilia (PWH) and healthcare professionals (HCPs). Greater access to resources and training in psychological services will be required throughout the treatment pathway. More specific guidance is required to define the implementation model, criteria for accreditation, and responsibilities of care centres. Furthermore, PWH may revisit discussions with HCPs multiple times pre-infusion, thus the patient journey is unlikely to be linear. Consideration of these challenges, and of potential strategies to address them, will be integral to optimising the future success of this promising therapy

Prevalence and predictors of exclusive breastfeeding in urban slums, Bihar

Objective: Various socio-cultural factors influence infant feeding practices and thus early childhood nutrition and child survival in India. This study aimed to examine the prevalence of exclusive breastfeeding, its promoters and barriers in urban slums of Bihar, India. Methods: We conducted a community based cross-sectional survey involving 297 mothers living in slum settlements in Bihar. Data were collected using structured questionnaire on exclusive breastfeeding practices, and the factors that could influence this. Descriptive analysis was done to estimate the prevalence of exclusive breastfeeding and regression model was performed to identify the predictors of exclusive breastfeeding. Results: Only 23% of mothers initiate breastfeeding within 1 hour of delivery and 27.6% mothers practise exclusive breastfeeding up to six months. Mother's education was found to be associated with duration of exclusive breastfeeding (OR 11, 95% CI 2-59). Term babies were more likely to be breastfed exclusively for six months than pre-term babies (OR 8.6, 95% CI 1.6-47.6). Antenatal care visits and completing immunization were significantly associated with duration of exclusive breastfeeding (P < 0.001). The majority of mothers acquire exclusive breastfeeding knowledge through television/radio (OR 68, 95% CI 5.5-832.5) and newspaper advertisements (OR 14, 95% CI 2.6-76). Conclusion: Prevalence of exclusive breastfeeding up to six months of age and early initiation of breastfeeding remains low in slums of Bihar. Exclusive breastfeeding and early initiation of breastfeeding rates could be improved by educating and counselling mothers during health facility contacts by primary care providers

Efficient Excitation of Micro/Nano Resonators and Their Higher Order Modes

We demonstrate a simple and flexible technique to efficiently activate micro/nano-electromechanical systems (MEMS/NEMS) resonators at their fundamental and higher order vibration modes. The method is based on the utilization of the amplified voltage across an inductor, L, of an LC tank resonant circuit to actuate the MEMS/NEMS resonator. By matching the electrical and mechanical resonances, significant amplitude amplification is reported across the resonators terminals. We show experimentally amplitude amplification up to twelve times, which is demonstrated to efficiently excite several vibration modes of a microplate MEMS resonator and the fundamental mode of a NEMS resonator

A Phase IB open-label, dose-escalation study of NUC 1031 in combination with carboplatin for recurrent ovarian cancer

Funding: The study was funded and the investigational drug NUC-1031 was supplied by NuCana plc.Purpose: NUC-1031 is a first-in-class ProTide modification of gemcitabine. In PRO-002, NUC‑1031 was combined with carboplatin in recurrent ovarian cancer (OC). Experimental Design: NUC-1031 was administered on days 1 & 8 with carboplatin on day 1 every 3 weeks for up to 6 cycles. Four dose cohorts of NUC-1031 (500, 625 and 750 mg/m2) with carboplatin (AUC4 or 5) were investigated. Primary endpoint was RP2CD. Secondary endpoints included safety, investigator-assessed objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS) and pharmacokinetics (PK). Results: 25 women with recurrent OC, a mean of 3.8 prior lines of chemotherapy and a median platinum-free interval (PFI) of 5 months (range: 7 - 451 days) were enrolled, 15/25 (60%) platinum-resistant; 9 (36%) partially platinum-sensitive and 1 (4%) platinum-sensitive. Of the 23 response-evaluable: there was 1 confirmed complete response (CR, 4%), 5 partial responses (PR, 17%) and 8 (35%) stable disease (SD). The ORR was 26% and CBR was 74% across all doses and 100% in the RP2CD cohort. Median PFS was 27.1 weeks. NUC-1031 was stable in the plasma and rapidly generated high intracellular dFdCTP levels that were unaffected by carboplatin. Conclusions: NUC-1031 combined with carboplatin is well tolerated in recurrent OC. Highest efficacy was observed at the RP2CD of 500 mg/m2 NUC-1031 on days 1 & 8 with AUC5 carboplatin day 1, every 3 weeks for 6 cycles. The ability to deliver carboplatin at AUC5 and the efficacy of this schedule even in patients with platinum-resistant disease makes this an attractive therapeutic combination.PostprintPeer reviewe

Effect of IoT capabilities and energy consumption behavior on green supply chain integration

The Internet of Things (IoT) is the next generation of internet-connected information communication technologies (ICT). IoT typically integrates supply chain activities to enhance green supply chain performance (GSCP). Since every organization has different IoT capabilities in comparison with other organizations, GSCP can enable supply chain integration activities for enhanced performance. The implementation of an IoT system can reduce the consumption of organizational resources like energy, electricity, and time and can increase the operational speed to gain better logistics and, ultimately, improved supply chain performance. This study has developed and empirically tested the relationship between IoT capabilities, energy consumption behavior (ECB), supply chain integration, green training (GT), and supply chain practices. Such a multidisciplinary relationship has not previously been established in the literature. The proposed study can fulfill the literature gap and opens new horizons for interdisciplinary research. Data used in this study are collected through offline and online survey methods. A total number of 250 out of 400 respondents participated in the survey. Data has been analyzed through partial least square-structure equation modeling (PLS-SEM) technique. The results of this study empirically test the developed model. IoT has a positive effect on supplier integration (SI), and customer integration (CI). Furthermore, SI and CI have a mediating role between IoT and GSCP, and GT has a positive impact on GSCP. It is concluded that the implementation of IoT can integrate CI and SI to increase GSCP. GT and ECB can ultimately improve GSCP. Additionally, the use of technology and GT can motivate employees to save energy and protect the environment to increase GSCP

Recombinant ADAMTS13 reduces abnormally up-regulated von Willebrand factor in plasma from patients with severe COVID-19

Thrombosis affecting the pulmonary and systemic vasculature is common during severe COVID-19 and causes adverse outcomes. Although thrombosis likely results from inflammatory activation of vascular cells, the mediators of thrombosis remain unconfirmed. In a cross-sectional cohort of 36 severe COVID-19 patients, we show that markedly increased plasma von Willebrand factor (VWF) levels were accompanied by a partial reduction in the VWF regulatory protease ADAMTS13. In all patients we find this VWF/ADAMTS13 imbalance to be associated with persistence of ultra-high-molecular-weight (UHMW) VWF multimers that are highly thrombogenic in some disease settings. Incubation of plasma samples from patients with severe COVID-19 with recombinant ADAMTS13 (rADAMTS13) substantially reduced the abnormally high VWF activity, reduced overall multimer size and depleted UHMW VWF multimers in a time and concentration dependent manner. Our data implicate disruption of normal VWF/ADAMTS13 homeostasis in the pathogenesis of severe COVID-19 and indicate that this can be reversed ex vivo by correction of low plasma ADAMTS13 levels. These findings suggest a potential therapeutic role for rADAMTS13 in helping restore haemostatic balance in COVID-19 patients

Prevalence of asymptomatic leishmania infection in people living with HIV and progression to symptomatic visceral leishmaniasis in Bihar, India

Intro People living with HIV (PLHIV) have an increased risk of developing visceral leishmaniasis (VL) and poor outcomes compared to HIV-negative individuals. Here, we aim to establish the prevalence and determinants of asymptomatic Leishmania infection (ALI) and the rate and risk factors for progression of ALI to VL in a cohort of PLHIV in Bihar, India. Methods We conducted a cross-sectional survey of PLHIV ≥18 years of age with no history or current diagnosis of VL or PKDL at anti-retroviral therapy centres within VL endemic districts of Bihar. ALI was defined as a positive rK39 ELISA, rK39 RDT, and/or qPCR. Additionally, the urinary Leishmania antigen ELISA was evaluated. The ALI and non-ALI cohorts were followed up every three months for 18 months in person and by telephone, respectively. Determinants for ALI were established using logistic regression model. Findings A total of 1,296 PLHIV enrolled in HIV care, 694 (53.6%) of whom were female and a median age of 39 years (IQR 33–46), were included in the analysis. The baseline prevalence of ALI was 7.4% (n=96). All 96 individuals were positive by rK39 ELISA, while 0.5% (n=6) and 0.4% (n=5) were positive by qPCR and rK39 RDT, respectively. Risk factors for ALI were CD4 counts <100 (OR 3.1; 95%CI 1.2–7.6) and CD4 counts 100-199 (OR=2.1; 95% CI: 1.1-4.0) compared to CD4 counts ≥300, and a household size ≥5 (OR=1.9; 95%CI: 1.1-3.1).Within the ALI cohort, four (3.7%) participants developed VL, compared to no progression in the non-ALI cohort. Mortality rates were higher in ALI compared to non-ALI (OR =2.7; 95% CI: 1.1-6.1). Conclusion The prevalence of ALI in PLHIV in VL endemic villages in Bihar was relatively high. However, the progression rate from ALI to VL in PLHIV was low. Patients with low CD4 counts and larger household size were at higher risk of ALI

An integrated workflow for robust alignment and simplified quantitative analysis of NMR spectrometry data

<p>Abstract</p> <p>Background</p> <p>Nuclear magnetic resonance spectroscopy (NMR) is a powerful technique to reveal and compare quantitative metabolic profiles of biological tissues. However, chemical and physical sample variations make the analysis of the data challenging, and typically require the application of a number of preprocessing steps prior to data interpretation. For example, noise reduction, normalization, baseline correction, peak picking, spectrum alignment and statistical analysis are indispensable components in any NMR analysis pipeline.</p> <p>Results</p> <p>We introduce a novel suite of informatics tools for the quantitative analysis of NMR metabolomic profile data. The core of the processing cascade is a novel peak alignment algorithm, called hierarchical Cluster-based Peak Alignment (CluPA). The algorithm aligns a target spectrum to the reference spectrum in a top-down fashion by building a hierarchical cluster tree from peak lists of reference and target spectra and then dividing the spectra into smaller segments based on the most distant clusters of the tree. To reduce the computational time to estimate the spectral misalignment, the method makes use of Fast Fourier Transformation (FFT) cross-correlation. Since the method returns a high-quality alignment, we can propose a simple methodology to study the variability of the NMR spectra. For each aligned NMR data point the ratio of the between-group and within-group sum of squares (BW-ratio) is calculated to quantify the difference in variability between and within predefined groups of NMR spectra. This differential analysis is related to the calculation of the F-statistic or a one-way ANOVA, but without distributional assumptions. Statistical inference based on the BW-ratio is achieved by bootstrapping the null distribution from the experimental data.</p> <p>Conclusions</p> <p>The workflow performance was evaluated using a previously published dataset. Correlation maps, spectral and grey scale plots show clear improvements in comparison to other methods, and the down-to-earth quantitative analysis works well for the CluPA-aligned spectra. The whole workflow is embedded into a modular and statistically sound framework that is implemented as an R package called "speaq" ("spectrum alignment and quantitation"), which is freely available from <url>http://code.google.com/p/speaq/</url>.</p

Prevalence of HCV and HIV infections in 2005-Earthquake-affected areas of Pakistan

<p>Abstract</p> <p>Background</p> <p>On October 8, 2005, an earthquake of magnitude 7.6 hit the Northern parts of Pakistan. In the post-earthquake scenario, overcrowding, improper sewage disposal, contamination of food and drinking water, hasty surgical procedures, and unscreened blood transfusions to earthquake victims most likely promotes the spread of infections already prevalent in the area.</p> <p>Objective</p> <p>The objective of the study reported here was to determine the prevalence of Human Immunodeficiency and Hepatitis C viruses (respectively, HIV and HCV) in the earthquake-affected communities of Pakistan. The samples were analyzed 2 months and then again 11 months after the earthquake to estimate the burden of HIV and HCV in these areas, and to determine any rise in the prevalence of these viral infections as a result of the earthquake.</p> <p>Methods</p> <p>Blood samples were initially collected during December, 2005 to March 2006, from 245 inhabitants of the earthquake-affected areas. These samples were screened for HCV and HIV, using immunochromatography and Enzyme-Linked Immuno-Sorbent Assay (ELISA).</p> <p>Results</p> <p>Out of 245 samples tested, 8 (3.26%) were found positive for HCV, and 0 (0.0%) for HIV, indicating the existence of HCV infection in the earthquake-stricken areas. The same methods were used to analyze the samples collected in the second round of screening in the same area, in September, 2006 – 11 months after the earthquake. This time 290 blood samples were collected, out of which 16 (5.51%) samples were positive for HCV, and 0 for HIV.</p> <p>Conclusion</p> <p>A slightly higher prevalence of HCV was recorded 11 months after the earthquake; this increase, however, was not statistically significant. None of the study participants was found HIV-infected.</p