JURNAL AGROTEKNOLOGI
Not a member yet
63896 research outputs found
Sort by
Book review: The Caliphate of Man: Popular Sovereignty in Modern Islamic Thought, by Andrew F. March
No full textClinical validation of optimised RT-LAMP for the diagnosis of SARS-CoV-2 infection
No full textWe have optimised a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay for the detection of SARS-CoV-2 from extracted RNA for clinical application. We improved the stability and reliability of the RT-LAMP assay by the addition of a temperature-dependent switch oligonucleotide to reduce self- or off-target amplification. We then developed freeze-dried master mix for single step RT-LAMP reaction, simplifying the operation for end users and improving long-term storage and transportation. The assay can detect as low as 13 copies of SARS-CoV2 RNA per reaction (25-μL). Cross reactivity with other human coronaviruses was not observed. We have applied the new RT-LAMP assay for testing clinical extracted RNA samples extracted from swabs of 72 patients in the UK and 126 samples from Greece and demonstrated the overall sensitivity of 90.2% (95% CI 83.8–94.7%) and specificity of 92.4% (95% CI 83.2–97.5%). Among 115 positive samples which Ct values were less than 34, the RT-LAMP assay was able to detect 110 of them with 95.6% sensitivity. The specificity was 100% when RNA elution used RNase-free water. The outcome of RT-LAMP can be reported by both colorimetric detection and quantifiable fluorescent reading. Objective measures with a digitized reading data flow would allow for the sharing of results for local or national surveillance
The starting-points for knowledge: Chrysippus on how to acquire and fortify insecure apprehension
No full textThis paper examines some neglected Chrysippean fragments on insecure apprehension (κατάληψις). First, I present Chrysippus’ account of how non-Sages can begin to fortify their insecure apprehension and upgrade it into knowledge (ἐπιστήμη). Next, I reconstruct Chrysippus’ explanation of how sophisms and counter-arguments lead one to abandon one’s insecure apprehension. One such counter-argument originates in the sceptical Academy and targets the Stoic claim that insecure apprehension can be acquired on the basis of custom (συνήθεια). I show how Chrysippus could defend the possibility of custom-based apprehension, while also denying that there is custom-based knowledge
SMARThealth Pregnancy: feasibility and acceptability of a complex intervention for high-risk pregnant women in rural India: protocol for a pilot cluster randomised controlled trial
No full textIntroduction: India is in the process of a major epidemiological transition towards non-communicable diseases. Cardiovascular disease (CVD) is the leading cause of death in women in India. Predisposing independent risk factors include pregnancy-related conditions, e.g. hypertensive disorders of pregnancy (HDP) and gestational diabetes (GDM) - also associated with significant perinatal mortality and morbidity. Early identification, referral and management of pregnant women at increased risk of future CVD may offer opportunities for prevention.
In rural India, Community Health Workers (CHWs) provide most antenatal and postnatal care. Innovative solutions are required to address integrated care for rural women during transitions between antenatal, postnatal and general health services. The George Institute’s SMARThealth Programme has shown that CHWs in rural India screening non-pregnant adults for cardiovascular risk, using a decision support system, is feasible. Building on this, we developed a targeted training programme for CHWs and a complex system-level intervention that uses mobile clinical decision support for CHWs and primary care doctors to screen high-risk pregnant women. In addition to addressing HDP and GDM, the intervention also screens for anaemia in pregnancy.
Methods/Design: A pilot study will be undertaken in two diverse rural districts of India: Jhajjar (Haryana) and Guntur (Andhra Pradesh). Two Primary Health Centre clusters will be randomised to intervention or control groups at each study site. The primary objective of this pilot study is to explore the feasibility and acceptability of the SMARThealth Pregnancy intervention. Secondary objectives are to estimate: a)prevalence rates of moderate to severe anaemia, HDPs and GDM at the study sites; b) referral and follow-up rates, and c) mean haemoglobin and blood pressure values at the routine six week postnatal visit. A process evaluation will be conducted to explore the acceptability of the SMARThealth Pregnancy intervention for pregnant women and healthcare workers using qualitative methods.
Discussion: It is anticipated that the findings of this pilot study will help determine the feasibility and acceptability of the SMARThealth Pregnancy intervention, and highlight how the intervention might be further developed for evaluation in a larger, cluster randomised controlled trial.
Trial registration: ClinicalTrials.gov Identifier: NCT0396895
Linking the Clinical Dementia Rating Scale-Sum of Boxes, the Clinician’s Interview-Based Impression Plus Caregiver Input, and the Clinical Global Impression Scale: evidence based on individual participant data from five randomized clinical trials of donepezil
No full textBackground: In patients with Alzheimer’s disease, global assessment scales, such as the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Clinician’s Interview-Based Impression Plus Caregiver Input (CIBI plus), and the Clinical Global Impression (CGI) are commonly used.
Objective: To clinically understand and interpret the associations between these scales, we examined the linkages for the total and change scores of CDR-SB, CIBI plus, and CGI.
Methods: Individual participant data (N = 2,198) from five pivotal randomized placebo-controlled trials of donepezil were included. Data were collected at baseline and scheduled visits for up to 6 months. Spearman’s correlation coefficients ρ were examined between corresponding total and change scores of simultaneous CDR-SB, CIBI plus, and CGI ratings. To link between the simultaneous ratings, equipercentile linking was used.
Results: We found strong evidence that the Spearman’s correlation coefficients between the CDR-SB and CGI, and CDR-SB and CIBI plus total scores were at least adequately correlated (ρ= 0.50 to 0.71, with p < 0.01). The correlation coefficients between the change scores of CDR-SB and CGI were deemed adequate for weeks 6 to 24 (ρ= 0.44 to 0.65); the remaining correlations were smaller in magnitude (ρ= 0.09 to 0.35). Overall, the linkages were in-line with expectations, e.g., CDR-SB range score of 3-4 (= very mild dementia) was linked to a CGI score of 3 (= mildly ill), and an increase of CDR-SB of 1 was linked to a change of 5 (= minimal worsening) in both CGI and CIBI plus.
Conclusion: The study findings can be useful for clinicians wishing to compare scores of different scales across patients. They can also help researchers understand results of studies using different scales and can facilitate meta-analyses, to increase statistical power
Metabolomics reveal potential natural substrates of AcrB in Escherichia coli and Salmonella enterica serovar Typhimurium
No full textIn the fight against antibiotic resistance, drugs that target resistance mechanisms in bacteria can be used to restore the therapeutic effectiveness of antibiotics. The multidrug resistance efflux complex AcrAB-TolC is the most clinically relevant efflux pump in Enterobacterales and is a target for drug discovery. Inhibition of the pump protein AcrB allows the intracellular accumulation of a wide variety of antibiotics, effectively restoring their therapeutic potency. To facilitate the development of AcrB efflux inhibitors, it is desirable to discover the native substrates of the pump, as these could be chemically modified to become inhibitors. We analyzed the native substrate profile of AcrB in Escherichia coli MG1655 and Salmonella enterica serovar Typhimurium SL1344 using an untargeted metabolomics approach. We analyzed the endo- and exometabolome of the wild-type strain and their respective AcrB loss-of-function mutants (AcrB D408A) to determine the metabolites that are native substrates of AcrB. Although there is 95% homology between the AcrB proteins of S. Typhimurium and E. coli, we observed mostly different metabolic responses in the exometabolomes of the S. Typhimurium and E. coli AcrB D408A mutants relative to those in the wild type, potentially indicating a differential metabolic adaptation to the same mutation in these two species. Additionally, we uncovered metabolite classes that could be involved in virulence of S. Typhimurium and a potential natural substrate of AcrB common to both species
Developing clinical prediction models when adhering to minimum sample size recommendations: the importance of quantifying bootstrap variability in tuning parameters and predictive performance
No full textRecent minimum sample size formula (Riley et al.) for developing clinical prediction models help ensure that development datasets are of sufficient size to minimise overfitting. While these criteria are known to avoid excessive overfitting on average, the extent of variability in overfitting at recommended sample sizes is unknown. We investigated this through a simulation study and empirical example to develop logistic regression clinical prediction models using unpenalised maximum likelihood estimation, and various post-estimation shrinkage or penalisation methods. While the mean calibration slope was close to the ideal value of one for all methods, penalisation further reduced the level of overfitting, on average, compared to unpenalised methods. This came at the cost of higher variability in predictive performance for penalisation methods in external data. We recommend that penalisation methods are used in data that meet, or surpass, minimum sample size requirements to further mitigate overfitting, and that the variability in predictive performance and any tuning parameters should always be examined as part of the model development process, since this provides additional information over average (optimism-adjusted) performance alone. Lower variability would give reassurance that the developed clinical prediction model will perform well in new individuals from the same population as was used for model development
Epstein-Barr virus-negative diffuse large B-cell post-transplant lymphoma in an Epstein-Barr virus-positive recipient
No full textPost-transplant lymphoproliferative disease (PTLD) can arise as a complication after solid organ transplantation. Epstein-Barr virus (EBV) infection is a known risk factor and is known to drive disease manifestation. PTLD can occur in EBV-negative recipients and with EBV-negative donor organs, however, EBV-negative PTLD pathogenesis is unknown. Here, we present PTLD presenting as intussusception in a patient with a historic simultaneous pancreas-kidney transplant (SPK). This case study presents the first documented case of EBV-negative post-transplant lymphoproliferative disease in an EBV-seropositive SPK recipient from an EBV-positive donor. Here we describe the diagnosis and management of this patient, discuss the differences between EBV positive and negative driven post-transplant lymphoproliferative disease, and highlight areas of research opportunity in the latter
Self-harm and the COVID-19 pandemic: a study of factors contributing to self-harm during lockdown restrictions
No full textIntroduction
The COVID-19 pandemic and resulting public health measures may have major impacts on mental health, including on self-harm. We have investigated what factors related to the pandemic influenced hospital presentations following self-harm during lockdown in England.
Method
Mental health clinicians assessing individuals aged 18 years and over presenting to hospitals in Oxford and Derby following self-harm during the period March 23rd to May 17, 2020 recorded whether the self-harm was related to the impact of COVID-19 and, if so, what specific factors were relevant. These factors were organized into a classification scheme. Information was also collected on patients’ demographic characteristics, method of self-harm and suicide intent.
Results
Of 228 patients assessed, in 46.9% (N = 107) COVID-19 and lockdown restrictions were identified as influencing self-harm. This applied more to females than males (53.5%, N = 68/127 v 38.6%, N = 39/101, χ2 = 5.03, p = 0.025), but there were no differences in age, methods of self-harm or suicide intent between the two groups. The most frequent COVID-related factors were mental health issues, including new and worsening disorders, and cessation or reduction of services (including absence of face-to-face support), isolation and loneliness, reduced contact with key individuals, disruption to normal routine, and entrapment. Multiple, often inter-connected COVID-related factors were identified in many patients.
Conclusions
COVID-related factors were identified as influences in nearly half of individuals presenting to hospitals following self-harm in the period following introduction of lockdown restrictions. Females were particularly affected. The fact that mental health problems, including issues with delivery of care, predominated has implications for organisation of services during such periods. The contribution of isolation, loneliness and sense of entrapment highlight the need for relatives, friends and neighbours to be encouraged to reach out to others, especially those living alone. The classification of COVID-related factors can be used as an aide-memoire for clinicians