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Travellers may be exposed to a wide range of different air pollutants during their journeys. In this study, personal exposures within vehicles and during active travel were tested in real-world conditions across nine different transport modes on journeys from London Paddington to Oxford City Centre, in the United Kingdom. The modes tested covered cycling, walking, buses, coaches, trains and private cars. Such exposures are relevant to questions of traveller comfort and safety in the context of airborne diseases such as COVID-19 and a growing awareness of the health, safety and productivity effects of interior air quality. Pollutants measured were particle number (PN), particle mass (PM), carbon dioxide (CO2) and speciated volatile organic compounds (VOCs), using devices carried on or with the traveller, with pumped sampling. Whilst only a relatively small number of journeys were assessed—inviting future work to assess their statistical significance—the current study highlights where a particular focus on exposure reduction should be placed. Real-time results showed that exposures were dominated by short-term spikes in ambient concentrations, such as when standing on a train platform, or at the roadside. The size distribution of particles varied significantly according to the situation. On average, the coach created the highest exposures overall; trains had mixed performance, while private cars and active transport typically had the lowest exposures. Sources of pollutants included both combustion products entering the vehicle and personal care products from other passengers, which were judged from desk research on the most likely source of each individual compound. Although more exposed to exhaust emissions while walking or cycling, the active traveller had the benefit of rapid dilution of these pollutants in the open air. An important variable in determining total exposure was the journey length, where the speed of the private car was advantageous compared to the relative slowness of the coach.

PDF file - 522K, Percentage of CD8+T cells recognizing MUC1 tetramer in HLA 2.1+ patients.

Purpose: A multiple myeloma vaccine has been developed whereby patient-derived tumor cells are fused with autologous dendritic cells, creating a hybridoma that stimulates a broad antitumor response. We report on the results of a phase II trial in which patients underwent vaccination following autologous stem cell transplantation (ASCT) to target minimal residual disease.Experimental Design: Twenty-four patients received serial vaccinations with dendritic cell/myeloma fusion cells following posttransplant hematopoietic recovery. A second cohort of 12 patients received a pretransplant vaccine followed by posttransplant vaccinations. Dendritic cells generated from adherent mononuclear cells cultured with granulocyte macrophage colony-stimulating factor, interleukin-4, and TNF-α were fused with autologous bone marrow–derived myeloma fusion cells using polyethylene glycol. Fusion cells were quantified by determining the percentage of cells that coexpress dendritic cell and myeloma fusion antigens.Results: The posttransplant period was associated with reduction in general measures of cellular immunity; however, an increase in CD4 and CD8+ myeloma-specific T cells was observed after ASCT that was significantly expanded following posttransplant vaccination. Seventy-eight percent of patients achieved a best response of complete response (CR)+very good partial response (VGPR) and 47% achieved a CR/near CR (nCR). Remarkably, 24% of patients who achieved a partial response following transplant were converted to CR/nCR after vaccination and at more than 3 months posttransplant, consistent with a vaccine-mediated effect on residual disease.Conclusions: The posttransplant period for patients with multiple myeloma provides a unique platform for cellular immunotherapy in which vaccination with dendritic cell/myeloma fusion fusions resulted in the marked expansion of myeloma-specific T cells and cytoreduction of minimal residual disease. Clin Cancer Res; 19(13); 3640–8. ©2013 AACR.

PDF file, 3806K, CD34-/lineage-cells from patient #25 were sorted into MUC1high and MUC1low populations.

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PDF file, 3013K, AML blasts from patient #20 harbored the trisomy 14 chromosomal abnormality.

Background. There is widespread acknowledgment amongst the rare disease community that effective communication strategies are lacking to explain diagnostic issues and therapeutic challenges to the public. The goal of this study was to objectively assess the communication needs of rare disease associations using validated techniques. - Methods. Sixty-minute structured interviews and objective analysis of transcribed responses were conducted and analyzed for 20 rare disease organizations. - Results. Associations uniformly agreed that effective communication was important to educate the public, advance advocacy and raise funds. However, there was no consensus as to how this should be achieved. Only seven of the 20 organizations had formal communication plans. Only few organizations had staff dedicated to external communication. - Conclusions. Strategic improvement in rare disease communication may increase the awareness of rare diseases and advance science. Communication challenges included staffing, funding, technological resources, training and expertise.

The current generation of Zero Emission Vehicle (ZEV) policies are designed to accelerate the transition away from conventional internal combustion engine (ICE) petrol and diesel vehicle fleets. However, the current focus on zero exhaust emissions and the lack of more detailed guidance regarding Non-Exhaust Emissions (NEEs) may mean that some of the trade-offs in transitioning to, e.g., Battery Electric Vehicle (BEV) fleets may be missed by many in the commercial sector. Here, as part of early work on the scoping of the First Bus EURO VI Diesel Vehicle (E6DV) to BEV fleet upgrades, we estimate E6DV total particulate emissions to be ca. 62–85 and 164–213 mg.veh−1.km−1 for PM2.5 and PM10, respectively, and that the majority, typically 93–97%, are NEEs. We also discuss the complex interaction between E6DV/BEV properties and estimate potential changes resulting from the transition to BEVs as ranging from a decrease of ca. 2–12% to an increase of ca. 12–50% depending on a combination of weight difference, regenerative brake performance and journey type. Finally, we propose metrics that would allow fleet operators more insight into a wider range of emission outcomes at the scoping stage of a fleet upgrade.

Although the consequences of sleep deficiency for obesity risk are increasingly apparent, experimental evidence is limited and there are no studies on body fat distribution.The purpose of this study was to investigate the effects of experimentally-induced sleep curtailment in the setting of free access to food on energy intake, energy expenditure, and regional body composition.Twelve healthy, nonobese individuals (9 males, age range 19 to 39 years) completed a randomized, controlled, crossover, 21-day inpatient study comprising 4 days of acclimation, 14 days of experimental sleep restriction (4 hour sleep opportunity) or control sleep (9 hour sleep opportunity), and a 3-day recovery segment. Repeated measures of energy intake, energy expenditure, body weight, body composition, fat distribution and circulating biomarkers were acquired.With sleep restriction vs control, participants consumed more calories (P = 0.015), increasing protein (P = 0.050) and fat intake (P = 0.046). Energy expenditure was unchanged (all P0.16). Participants gained significantly more weight when exposed to experimental sleep restriction than during control sleep (P = 0.008). While changes in total body fat did not differ between conditions (P = 0.710), total abdominal fat increased only during sleep restriction (P = 0.011), with significant increases evident in both subcutaneous and visceral abdominal fat depots (P = 0.047 and P = 0.042, respectively).Sleep restriction combined with ad libitum food promotes excess energy intake without varying energy expenditure. Weight gain and particularly central accumulation of fat indicate that sleep loss predisposes to abdominal visceral obesity. (Sleep Restriction and Obesity; NCT01580761).

This article documents thermophysiological patterns associated with migraine episodes, where the inner canthi and supraorbital temperatures drop significantly compared to normal conditions. These temperature drops are likely due to vasoconstriction of the ophthalmic arteries under the inner canthi and sympathetic activation of the eccrine glands in the supraorbital region, respectively. The thermal patterns were observed on eight migraine patients and meticulously quantified using advance computational methods, capable of delineating small anatomical structures in thermal imagery and tracking them automatically over time. These methods open the way for monitoring migraine episodes in nonclinical environments, where the patient maintains directional attention, such as his/her computer at home or at work. This development has the potential to significantly expand the operational envelope of migraine studies.

In a drive to achieve net zero emissions, U.K. transport decarbonisation policies are predominantly focussed on measures to promote the uptake and use of electric vehicles (EVs). This is reflected in the COP26 Transport Declaration signed by 38 national governments, alongside city region governments, vehicle manufacturers and investors. However, emerging evidence suggests that EVs present multiple challenges for air quality, mobility and health, including risks from non-exhaust emissions (NEEs) and increasing reliance on vehicles for short trips. Understanding the interconnected links between electric mobility, human health and the environment, including synergies and trade-offs, requires a whole systems approach to transport policymaking. In the present paper, we describe the use of Participatory Systems Mapping (PSM) in which a diverse group of stakeholders collaboratively constructed a causal model of the U.K. surface transport system through a series of interactive online workshops. We present the map and its analysis, with our findings illustrating how unintended consequences of EV-focussed transport policies may have an impact on air quality, human health and important social functions of the transport system. We conclude by considering how online participatory causal modelling techniques could be effectively integrated with empirical metrics to facilitate effective policy design and appraisal in the transport sector.

Objective Little is known about long-term metabolic (energy expenditure) adaptation after bariatric surgery. Methods Resting metabolic rate under basal conditions (RMR), total daily energy expenditure (TDEE), and body composition were measured in 25 participants in the Longitudinal Assessment of Bariatric Surgery-2. Results Six months after surgery, BMI (±SD) decreased (47 ± 6 kg/m2 to 37 ± 5 kg/m2 ), body fat went from 48% ± 6% to 40% ± 6% fat, and fat-free mass went from 67 ± 9 kg to 60 ± 9 kg. In absolute terms, RMR and TDEE both decreased significantly (1,730 ± 278 kcal/d vs. 1,430 ± 200 kcal/d and 2,879 ± 544 kcal/d vs. 2,369 ± 304 kcal/d), and the achieved energy balance was -1,293 ± 355 kcal/d. Sixteen of these participants underwent repeated measures at ∼24 months; TDEE decreased 6 months postoperatively (2,957 ± 540 kcal/d to 2,423 ± 324 kcal/d; P = 0.0003), but at ∼24 months, TDEE (2,602 ± 471 kcal/d) was not significantly different compared with month 6. The average negative energy balance from baseline to month 24 was -379 ± 131 kcal/d. Conclusions RMR and TDEE fall precipitously in the first 6 months after bariatric surgery, but these adaptive changes were no longer significant after 2 years.

Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti–T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. Patients received either ATLG or placebo 20 mg/kg per day on days −3, −2, −1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study end point was moderate-severe cGVHD-free survival. Results Despite a reduction in grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v 33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free survival between ATLG and placebo was found (2-year estimate: 48% v 44%, respectively; P = .47). Both progression-free survival (PFS) and overall survival (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [ P = .034], respectively). Multivariable analysis confirmed that ATLG was associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026) and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.

Myeloid-derived suppressor cells (MDSCs) play a critical role in promoting immune tolerance and disease growth. The mechanism by which tumor cells evoke the expansion of MDSCs in acute myeloid leukemia (AML) has not been well described. We have demonstrated that patients with AML exhibit increased presence of MDSCs in their peripheral blood, in comparison with normal controls. Cytogenetic studies demonstrated that MDSCs in patients with AML may be derived from leukemic or apparently normal progenitors. Engraftment of C57BL/6 mice with TIB-49 AML led to an expansion of CD11b+ Gr1+ MDSCs in bone marrow and spleen. Coculture of the AML cell lines MOLM-4, THP-1 or primary AML cells with donor peripheral blood mononuclear cells elicited a cell contact-dependent expansion of MDSCs. MDSCs were suppressive of autologous T-cell responses as evidenced by reduced T-cell proliferation and a switch from a Th1 to a Th2 phenotype. We hypothesized that the expansion of MDSCs in AML is accomplished by tumor-derived extracellular vesicles (EVs). Using tracking studies, we demonstrated that AML EVs are taken-up myeloid progenitor cells, resulting in the selective proliferation of MDSCs in comparison with functionally competent antigen-presenting cells. The MUC1 oncoprotein was subsequently identified as the critical driver of EV-mediated MDSC expansion. MUC1 induces increased expression of c-myc in EVs that induces proliferation in the target MDSC population via downstream effects on cell cycle proteins. Moreover, we demonstrate that the microRNA miR34a acts as the regulatory mechanism by which MUC1 drives c-myc expression in AML cells and EVs.