Using InVivoStat to perform the statistical analysis of experiments

The need to improve reproducibility and reliability of animal experiments has led some journals to increase the stringency of the criteria that must be satisfied before manuscripts can be considered suitable for publication. In this article we give advice on experimental design, including minimum group sizes, calculating statistical power and avoiding pseudo-replication, which can improve reproducibility. We also give advice on normalisation, transformations, the gateway analysis of variance strategy and the use of p-values and confidence intervals. Applying all these statistical procedures correctly will strengthen the validity of the conclusions. We discuss how InVivoStat, a free-to-use statistical software package, which was designed for life scientists, especially animal researchers, can be used to help with these principles

Anisotropic P‐wave attenuation measured from a multi‐azimuth surface seismic reflection survey

A system of aligned vertical fractures produces azimuthal variations in stacking velocity and amplitude variation with offset, characteristics often reported in seismic reflection data for hydrocarbon exploration. Studies of associated attenuation anisotropy have been mostly theoretical, laboratory or vertical seismic profiling based. We used an 11 common‐midpoint‐long portion of each of four marine surface‐seismic reflection profiles, intersecting each other at 45° within circa 100 m of a common location, to measure the azimuthal variation of effective attenuation, Q−1eff and stacking velocity, in a shallow interval, about 100 m thick, in which consistently orientated vertical fracturing was expected due to an underlying salt diapirism. We found qualitative and quantitative consistency between the azimuthal variation in the attenuation and stacking velocity, and published amplitude variation with offset results. The 135° azimuth line showed the least apparent attenuation (1000 Q−1eff= 16 ± 7) and the fastest stacking velocity, hence we infer it to be closest to the fracture trend: the orthogonal 45° line showed the most apparent attenuation (1000Q−1eff= 52 ± 15) and slowest stacking velocity. The variation of Q−1eff with azimuth φ is well fitted by 1000Q−1eff= 34 − 18cos[2(φ+40°)] giving a fracture direction of 140 ± 23° (±1SD, derived from ‘bootstrapping’ fits to all 114 combinations of individual common‐midpoint/azimuth measurements), compared to 134 ± 47° from published amplitude variation with offset data. The effects of short‐window spectral estimation and choices of spectral ratio bandwidth and offset ranges used in attenuation analysis, individually give uncertainties of up to ±13° in fracture direction. This magnitude of azimuthal variation can be produced by credible crack geometries (e.g., dry cracks, radius 6.5 m, aspect ratio 3 × 10−5, crack density 0.2) but we do not claim these to be the actual properties of the interval studied, because of the lack of well control (and its consequences for the choice of theoretical model and host rock physical properties) and the small number of azimuths available here

Mathematical modelling of the impact of adolescent/adult tuberculosis vaccines to inform global, national, and subnational policy and delivery

Background: Tuberculosis is a leading cause of death worldwide from a single infectious agent, with an estimated 10.6 million new cases and 1.6 million deaths in 2021. The global burden of tuberculosis is highest in low- and middle-income countries (LMICs), and the largest burden of disease by country is found in India, accounting for around 30% of cases and deaths in 2021. New tuberculosis vaccines could play a key role in reducing the global burden of tuberculosis. As of 2023, there were sixteen candidates in clinical trials, and the vaccine candidate M72/AS01E and BCG-revaccination are of particular interest, as they have recently completed Phase IIb trials with positive results. There is optimism that a new vaccine or a recommendation for policy change for an existing vaccine could come within the next decade. It is important for decision makers to have information about the potential health and economic impacts of tuberculosis vaccines to support development and planning for vaccine introduction. However, decision makers will require different information to make informed decisions depending on their role. Global decision makers need to know the potential value of introducing tuberculosis vaccines to encourage continued development of candidates, whereas decision makers for national and subnational governments need information on country-level implementation of vaccines, such as M72/AS01E and BCG-revaccination, and the impact of any regional specific differences. The overall aim of this thesis is to use mathematical modelling to generate appropriate evidence to provide decision makers globally, and at various levels of government in India, with estimates of health and economic impact to support tuberculosis vaccine development, policy, and introduction. Methods: I developed a new tuberculosis model to incorporate recent advances in the knowledge of tuberculosis natural history, including subclinical disease and self-clearance. To support decision makers globally and encourage investment in vaccine candidates, I independently calibrated the model to 105 LMICs representing 93% of the global tuberculosis burden. I estimated the potential health impacts of vaccines meeting the WHO Preferred Product Characteristics for New Tuberculosis Vaccines by WHO region, World Bank income group, and WHO burden group. To support country-specific decisions regarding vaccine delivery of M72/AS01E and BCG-revaccination in India overall, I developed a sophisticated country-level model to simulate tuberculosis vaccine introduction in India. The country-level model incorporated differences in public and private sector treatment, and calibration targets over time to constrain long-term dynamics. I simulated M72/AS01E and BCG-revaccination scenarios exploring uncertainty in product characteristics and delivery. I estimated reductions in tuberculosis cases and deaths by each scenario, as well as costs and cost-effectiveness from the health system and societal perspectives. Finally, to assess potential differences between delivery strategies for M72/AS01E and BCGrevaccination within India, I developed subnational models for Delhi and Gujarat—two regions within India estimated to have the highest and lowest adult prevalence of tuberculosis disease respectively, incorporating regional specific differences in demography, infection prevalence, and treatment. I simulated M72/AS01E and BCG-revaccination scenarios to quantify and compare the predicted health and economic impacts. Results: Results from the multi-country modelling suggest that introducing new tuberculosis vaccines aligned with the WHO Preferred Product Characteristics could have a substantial impact in LMICs. Rapid introduction of an adolescent/adult vaccine could prevent up to 76.0 million cases and 8.5 million deaths before 2050. A booster infant vaccine could prevent up to 18.0 million cases and 2.6 million deaths before 2050. Evaluating the delivery of specific vaccine candidates through country-level modelling in India, M72/AS01E vaccines could avert up to 19.3 million cases and 3.1 million deaths, and BCGrevaccination could avert up to 15.2 million cases and 2.6 million deaths by 2050. Nearly all vaccine scenarios were cost-effective at the most conservative country-level threshold compared to no new vaccine introduction, and the average annual cost of M72/AS01E vaccination was around four times greater than that of BCG-revaccination. When comparing delivery strategies for specific vaccine candidates using the subnational models within India, M72/AS01E vaccines could avert up to 1.0 million cases in Delhi and 575 thousand cases in Gujarat, and BCG-revaccination could avert up to 626 thousand cases in Delhi and 222 thousand cases in Gujarat. Both subnational models predicted a larger impact of M72/AS01E vaccines than the impact of BCG-revaccination. The relative impact of BCG-revaccination for scenarios delivering the vaccine to older ages or all adults was higher in Gujarat compared to Delhi. Conclusions: New tuberculosis vaccines are likely to have a substantial health and economic impact globally and in India. The considerable reduction in cases and deaths estimated from multi-country modelling of tuberculosis vaccines in 105 LMICs supports the case for sustained investment in tuberculosis vaccine candidates throughout the pipeline to ensure success. While uncertainty in the actual vaccine characteristics exists, the modelling suggests that including a vaccination campaign, as well as rapidly introducing and scaling-up a new vaccine is crucial to obtain rapid impact by 2050. Country-level modelling in India and subnational modelling in Delhi and Gujarat of M72/AS01E and BCG-revaccination were estimated to be impactful and cost-effective. Knowledge of the population demographics and age-specific prevalence of infection will be important for decision makers in India to consider when considering delivery strategies for vaccines which are not effective for all infection statuses. Overall, these results suggest tuberculosis vaccines could be impactful and effective no matter the geographic scale of analysis, but at the national and subnational level, vaccine delivery strategies need to take into account regional variation in epidemiology and health care access to allow for the greatest possible impact. The evidence generated in this thesis has and can support global decision makers with vaccine investment decisions, and the Indian government with decisions regarding policy and vaccine delivery

Photon indistinguishability measurements under pulsed and continuous excitation

The indistinguishability of successively generated photons from a single quantum emitter is most commonly measured using two-photon interference at a beam splitter. Whilst for sources excited in the pulsed regime the measured bunching of photons reflects the full wavepacket indistinguishability of the emitted photons, for continuous wave (cw) excitation the inevitable dependence on detector timing resolution and driving strength obscures the underlying photon interference process. Here we derive a method to extract the photon indistinguishability from cw measurements by considering the relevant correlation functions. The equivalence of both methods is experimentally verified through comparison of cw and pulsed excitation of an archetypal source of photons, a single molecule

Resident Memory T Cells (TRM) Are Abundant in Human Lung: Diversity, Function, and Antigen Specificity

Recent studies have shown that tissue resident memory T cells (TRM) are critical to antiviral host defense in peripheral tissues. This new appreciation of TRM that reside in epithelial tissues and mediate host defense has been studied most extensively in skin: adult human skin contains large numbers of functional TRM that express skin specific markers. Indeed, more than twice as many T cells reside in skin as in peripheral blood. This T cell population has a diverse T cell receptor repertoire, and can produce a broad array of cytokines. More recently, we have begun to examine other epithelial tissues for the presence of resident T cells. In the present study, we asked whether analogous populations of resident T cells could be found in human lung. We were able to demonstrate abundant resident T cells in human lung-more than 10 billion T cells were present. Lung T cells were largely of the effector memory T cell (TEM) phenotype, though small numbers of central memory T cells (TCM) and T regulatory cells (Treg) could be identified. Lung T cells had a diverse T cell receptor repertoire and subsets produced IL-17, IL-4, IFNγ, as well as TNFα. A significant number of lung TRM CD4+Th cells produced more than one cytokine, identifying them as “multifunctional” Th1 type cells. Finally, lung TRM, but not TRM resident to skin or T cells from blood, proliferated in response to influenza virus. This work suggests that normal human lung contains large numbers of TRM cells, and these cells are poised to respond to recall antigens previously encountered through lung mucosa. This population of T cells may contribute to the pathogenesis of asthma and other T cell mediated lung diseases

Not all systematic reviews are systematic: A meta-review of the quality of systematic reviews for non-invasive remote monitoring in heart failure

We carried out a critical appraisal and synthesis of the systematic reviews and meta-analyses of remote monitoring for heart failure. A comprehensive literature search identified 65 relevant publications from 3333 citations. Seventeen studies fulfilled the inclusion and exclusion criteria. Seven (41%) systematic reviews pooled results for meta-analysis. Eight (47%) considered all non-invasive remote monitoring strategies. Five (29%) focused on telemonitoring. Four (24%) included both non-invasive and invasive technologies. The reviews were appraised by two independent reviewers for their quality and risk of bias using the AMSTAR tool. According to the AMSTAR criteria, ten (58%) systematic reviews were of poor methodological quality. In the high quality reviews, the relative risk of mortality in patients who received remote monitoring ranged from 0.53 to 0.88. The high quality reviews also reported that remote monitoring reduced the relative risk of all-cause (0.52 to 0.96) and heart failure-related hospitalizations (0.72 to 0.79) and, as a consequence, healthcare costs. However, further research is required before considering widespread implementation of remote monitoring. The subset of the heart failure population that derives the most benefit from intensive monitoring, the best technology, and the optimum duration of monitoring, all need to be identified. © The Author(s) 2013

A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic

Sewage, a complex mixture of organic and inorganic chemicals, is considered to be a major source of environmental pollution. A random screen of 20 organic man-made chemicals present in liquid effluents revealed that half appeared able to interact with the estradiol receptor. This was demonstrated by their ability to inhibit binding of 17 beta-estradiol to the fish estrogen receptor. Further studies, using mammalian estrogen screens in vitro, revealed that the two phthalate esters butylbenzyl phthalate (BBP) and di-n-butylphthalate (DBP) and a food antioxidant, butylated hydroxyanisole (BHA) were estrogenic; however, they were all less estrogenic than the environmental estrogen octylphenol. Phthalate esters, used in the production of various plastics (including PVC), are among the most common industrial chemicals. Their ubiquity in the environment and tendency to bioconcentrate in animal fat are well known. Neither BBP nor DBP were able to act as antagonists, indicating that, in the presence of endogenous estrogens, their overall effect would be cumulative. Recently, it has been suggested that environmental estrogens may be etiological agents in several human diseases, including disorders of the male reproductive tract and breast and testicular cancers. The current finding that some phthalate compounds and some food additives are weakly estrogenic in vitro, needs to be supported by further studies on their effects in vivo before any conclusions can be made regarding their possible role in the development of these condition

Gesture Detection Towards Real-Time Ergonomic Analysis for Intelligent Automation Assistance

Manual handling involves transporting of load by hand through lifting or lowering and operators on the manufacturing shop floor are daily faced with constant lifting and lowering operations which leads to Work-Related Musculoskeletal Disorders. The trend in data collection on the Shop floor for ergonomic evaluation during manual handling activities has revealed a gap in gesture detection as gesture triggered data collection could facilitate more accurate ergonomic data capture and analysis. This paper presents an application developed to detect gestures towards triggering real-time human motion data capture on the shop floor for ergonomic evaluations and risk assessment using the Microsoft Kinect. The machine learning technology known as the discrete indicator—precisely the AdaBoost Trigger indicator was employed to train the gestures. Our results show that the Kinect can be trained to detect gestures towards real-time ergonomic analysis and possibly offering intelligent automation assistance during human posture detrimental tasks