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Background: We investigated the feasibility of dose-dense neoadjuvant chemotherapy (NACT) with paclitaxel and carboplatin before radical chemoradiation (CRT) and assessed the response rate to such a regimen. Methods: CxII is a single-arm phase II trial of 46 patients, with locally advanced cervical cancer (stage Ib2-IVa). Patients received dose-dense carboplatin (AUC2) and paclitaxel (80 mg m −2 ) weekly for six cycles followed by CRT (40 mg m −2 of weekly cisplatin, 50.4 Gy, 28 fractions plus brachytherapy). The primary end point was response rate 12 weeks post-CRT. Results: Baseline characteristics were: median age at diagnosis 43 years; 72% squamous, 22% adenocarcinoma and 7% adenosquamous histologies; FIGO stage IB2 (11%), II (50%), III (33%), IV (7%). Complete or partial response rate was 70% (95% CI: 54–82) post-NACT and 85% (95% CI: 71–94) post-CRT. The median follow-up was 39.1 months. Overall and progression-free survivals at 3 years were 67% (95% CI: 51–79) and 68% (95% CI: 51–79), respectively. Grade 3/4 toxicities were 20% during NACT (11% haematological, 9% non-haematological) and 52% during CRT (haematological: 41%, non-haematological: 22%). Conclusion: A good response rate is achieved by dose-dense weekly NACT with carboplatin and paclitaxel followed by radical CRT. This treatment regimen is feasible as evidenced by the acceptable toxicity of NACT and by the high compliance to radiotherapy (98%).

The UK has introduced legislation that requires net-zero greenhouse gas emissions to be achieved by 2050. Improving the energy efficiency of homes is a key objective to help reach this target, and the UK government’s Clean Growth Strategy aims to get many homes up to an Energy Performance Certificate (EPC) Band of C by 2035. The relationship between home energy-efficiency and occupant health and wellbeing remains an area of ongoing research. This paper explores the nexus between home energy efficiency, energy consumption and self-reported health—an indicator of the general health and wellbeing of the population. We focus on Greater London through secondary data analysis. Energy-efficiency ratings and air infiltration rates of dwellings, derived from EPCs, were aggregated and matched to local area self-reported health and energy consumption data obtained from the Greater London Authority’s (GLA) Lower Layer Super Output Area (LSOA) Atlas database. Our regression model indicates that improving the energy efficiency (SAP) rating by 10 points for a typical home may reduce household gas consumption by around 7% (95% CIs: 2%, 14%). Beta regression finds a positive, but not statistically significant association between median SAP rating and the proportion of the population reporting ‘good or very good’ health when considering all Greater London LSOAs (z score = 0.60, p value = 0.55). A statistically significant positive association is observed however when repeating the analysis for the lowest income quartile LSOAs (z score = 2.03, p value = 0.04). This indicates that the least well-off may benefit most from home energy efficiency programs. A statistically significant positive association is also observed for the relationship between self-reported health and air infiltration rates (z score = 2.62, p value = 0.01). The findings support existing evidence for the predominantly naturally ventilated UK housing stock, suggesting that home energy efficiency measures provide a co-benefit for occupant health provided that adequate air exchange is maintained.

Throughout the world there are problems recruiting ethnic minority patients into cancer clinical trials. A major barrier to trial entry may be distrust of research and the medical system. This may be compounded by the regulatory framework governing research with an emphasis on written consent, closed questions and consent documentation, as well as fiscal issues. The Leicester UK experience is that trial accrual is better if British South Asian patients are approached by a senior doctor rather than someone of perceived lesser hierarchical status and a greater partnership between the hospital and General Practitioner may increase trial participation of this particular ethnic minority. In Los Angeles, USA, trial recruitment was improved by a greater utilisation of Hispanic staff and a Spanish language-based education programme. Involvement of community leaders is essential. While adhering to national, legal and ethnical standards, information sheets and consent, it helps if forms can be tailored towards the local ethnic minority population. Written translations are often of limited value in the recruitment of patients with no or limited knowledge of English. In some cultural settings, tape-recorded verbal consent (following approval presentations) may be an acceptable substitute for written consent, and appropriate legislative changes should be considered to facilitate this option. Approaches should be tailored to specific minority populations, taking consideration of their unique characteristics and with input from their community leadership.

The first phase 2 gene therapy trial for HIV-1 has shown some promising signs. There's a long way to go before this would be a viable approach in people with HIV—this trial did not show a statistically significant difference in viral load at the primary end point–but other analyses did reveal that the gene therapy seemed to have a modest, but statistically significant, effect at reducing viral load in the treated subjects versus the placebo arm. The study also provides some clues about what to improve in the future. Gene transfer has potential as a once-only treatment that reduces viral load, preserves the immune system and avoids lifetime highly active antiretroviral therapy. This study, which is to our knowledge the first randomized, double-blind, placebo-controlled, phase 2 cell-delivered gene transfer clinical trial, was conducted in 74 HIV-1–infected adults who received a tat - vpr –specific anti-HIV ribozyme (OZ1) or placebo delivered in autologous CD34 + hematopoietic progenitor cells. There were no OZ1-related adverse events. There was no statistically significant difference in viral load between the OZ1 and placebo group at the primary end point (average at weeks 47 and 48), but time-weighted areas under the curve from weeks 40–48 and 40–100 were significantly lower in the OZ1 group. Throughout the 100 weeks, CD4 + lymphocyte counts were higher in the OZ1 group. This study indicates that cell-delivered gene transfer is safe and biologically active in individuals with HIV and can be developed as a conventional therapeutic product.

Housing is an important modifier of outdoor environmental hazards due to features such as the amount of passive and active ventilation a dwelling receives, the proportion of the façade that is glazed and the building’s thermal insulation levels. Using Artificial Neural Networks based on an indoor building physics model, we simulate indoor temperature and air pollution concentrations in ~15 million English and Welsh dwellings and assess how exposure to indoor hazards varies for different population groups. The model is derived using simulations from the dynamic thermal modelling tool EnergyPlus , taking a spatially-distributed housing stock as input. Results are linked to the latest 2021 Census data on area-measures of population demographics to assess if vulnerable subgroups bear a disproportionate risk from indoor environmental hazards. We find neighbourhoods in England and Wales with a higher proportion of infants, ethnic minorities and income-deprived populations experience higher two-day maximum indoor temperatures in summertime; whilst more ethnically diverse areas have elevated annual average indoor concentrations of outdoor-sourced PM 2.5 . Areas with a higher proportion of those aged 65+ had a lower standardised indoor temperature (SIT) in winter, increasing the risk of fuel poverty. We then implement a stock-wide, home energy retrofit, in line with national decarbonisation targets. Results suggest energy-efficient building interventions may exacerbate heat inequalities without the provision of external shading, but improve population exposure to winter indoor temperatures and indoor concentrations of ambient-sourced PM 2.5 .

Trauma accounts for 20% of deaths in pregnant women. Injury characterisation and outcome in pregnant women following trauma is poorly described. To understand and inform optimum care of this key injury population, a study was conducted using the Trauma Audit Research Network (TARN) database. In total, 341 pregnant and 26,774 non-pregnant female patients aged 15 to 46 years were identified for comparison from the TARN database. Mortality, cross-sectional imaging, blood product administration and EQ-5D scores were compared between the two groups. Mechanism of injury, Injury Severity Score (ISS) and mortality rate before and after the creation of regional trauma networks were reported for pregnant patients. Pregnancy was recorded in 1.3% (341/27,115) of included patients, with the most common cause of injury being road traffic collisions. A reduction in crude maternal mortality was observed over the course of the study period (7.3% to 2.9%). Baseline mean EQ-5D (0.47) and EQ-VAS (54.08) improved to 0.81 ( < 0.001) and 85.75 ( = 0.001), respectively, at 6 months following injury. The incidence of trauma in pregnancy is small and mortality in injured pregnant women decreased over the study period. Pregnant patients have significantly improved patient-reported outcome measures 6 months after injury although this is limited in impact because of poor response rates and outcome reporting. Construction and validation of tools aiding in outcome reporting will help considerably in understanding further gains in the care of pregnant women.

This paper explores the impact of different approaches to aggregating the indoor concentration of fine particulate matter (PM2.5) in a case study home. Indoor- and outdoor-sourced PM2.5 was modelled in CONTAM-EnergyPlus for a bungalow occupied by a family of four in Plymouth, England. Simulations were conducted assuming energy efficiency levels typical of a 1950s home and following retrofit. Pollutants were modelled at a 5-min temporal resolution in bedrooms, kitchen and living room and aggregated according to four metrics: (i) household arithmetic mean concentration, (ii) household time-weighted mean concentration, (iii) arithmetic mean of individual exposure, and (iv) household arithmetic mean exposure. Comparing the household metrics revealed differences of up to 50.0 % (3.6 μg/m3) for the pre-retrofit model, which remained largely consistent following retrofit. When comparing against individual exposure, differences were observed for all three metrics and reached 55.6% (9.1 μg/m3) for the pre-retrofit model, and 50.6% (8.7 μg/m3) for the post-retrofit model. Approaches (i) and (ii) consistently underpredicted individual exposure. Further, the differences were greatest for the time-weighted mean method, suggesting that taking into consideration the total time that each room is occupied but not when it is occupied will not necessarily provide a more accurate description of occupant exposure compared to the simple arithmetic mean. To better represent individual exposure, data on occupant presence is required.

The impact of the COVID-19 pandemic on building energy use has been studied across various countries. However, with the growing trend toward flexible working and the rising frequency of climate-induced extreme weather events, the combined effects of these factors on future energy use remain largely unexplored. This study develops a methodology to investigate the resilience of the UK’s low-income housing sector in response to the combined impacts of climate change and pandemics. Energy use of 7 residential archetypes (Bungalow, Converted flat, Detached, Semi-detached, Mid-terrace, End-terrace, and Low-rise buildings) under 13 future climate scenarios for the year 2050 and using detailed pandemic occupancy profiles is simulated. Specific thermo-physical properties and construction details of the archetypes (e.g., U-values, building envelope, HVAC system characteristics, boundary conditions, etc.) are obtained from English Housing Survey (EHS) data to develop a multi-zone model using the EnergyPlus software. The aim is to simulate hourly energy use (heating & hot water, electricity, and cooling) considering future climate scenarios (for the year 2050 as extreme warm and extreme cold) and pandemic measures for (1) Standard Retrofitting Scenario (SRS) and (2) Deep Retrofitting Scenario (DRS) for different housing archetypes. The results show that the increase in cooling during the extreme warm year (EWY) - and under the extended 14-hour to 24-hour potential pandemic occupancy schedule - is significantly greater than the rise in heat consumption during the extreme cold year (ECY) but varies across the housing archetypes. Furthermore, the results show retrofitting can result in higher cooling requirements. Across the three retrofitting scenarios, energy use for cooling is highest under the DRS, while the base case scenario (BCS), no retrofitting, shows the lowest energy use for cooling. Implementing passive cooling measures, such as shading, ventilation, and using cool/green roofs, may offset the increase in cooling demand caused by retrofitting.

Global efforts to reduce greenhouse gas emissions from buildings while also improving their environmental resilience have intensified. These efforts are often supported by building stock models which can inform policymakers on the impact of policies on energy consumption, greenhouse gas emissions and the indoor environment. The input values of such models are commonly informed by reference tables, which can result in inaccurate specification and incomplete representation of the distribution of possible values. In this modelling case study of a semi-detached dwelling archetype, the influence of using a reference U-value (2.1 W/(m 2 K)) for solid walls in England on heat-related mortality rate is compared to a probabilistic specification based on empirical evidence (median = 1.7W/(m 2 K)). Using the theoretical reference U-value generally resulted in a lower indoor overheating risk compared to the use of the empirically derived U-values pre-retrofit, but a larger increase in heat-related mortality rate following internal wall insulation (1.20%) than the use of the empirical median (0.94%, 95 % Confidence Interval = 0.87–0.99 %). This highlights the potentially significant implications of using fixed reference values. Future work will employ this probabilistic framework on multiple influential parameters.

In this work we evaluate the potential of selected environmental strategies in reducing air pollution and summertime indoor overheating. Associated changes in mortality rates are also calculated for older adults in London. Reducing these risks for vulnerable groups is an immediate priority and given that seniors spend most of their time indoors, our focus is on strategies that prioritize the transformation of residential environments for indoor thermal comfort and air quality improvements. For each strategy, we develop specific scenarios related to building adaptations and test potential reductions on indoor overheating and pollutant exposures from outdoor sources (PM 2.5 ), as well as on senior mortality through the CRAFT tool (Cities Rapid Assessment Framework for Transformation). We then pick the scenarios with highest impacts on mortality, aiming to formulate effective policy recommendations for Greater London. Preliminary results suggest that environmental policies related to the installation of shading could have the highest reduction in heat and pollution-related senior mortality, followed by moderate effects due to building insulation retrofits and the greening of roofs. With an increasing ageing population in the UK and beyond, our work highlights the need for city-level policies to address building modifications, considering the importance of indoor spaces for older adults.