Continuing benefits of the Montreal Protocol and protection of the stratospheric ozone layer for human health and the environment.

The protection of Earth's stratospheric ozone (O3) is an ongoing process under the auspices of the universally ratified Montreal Protocol and its Amendments and adjustments. A critical part of this process is the assessment of the environmental issues related to changes in O3. The United Nations Environment Programme's Environmental Effects Assessment Panel provides annual scientific evaluations of some of the key issues arising in the recent collective knowledge base. This current update includes a comprehensive assessment of the incidence rates of skin cancer, cataract and other skin and eye diseases observed worldwide; the effects of UV radiation on tropospheric oxidants, and air and water quality; trends in breakdown products of fluorinated chemicals and recent information of their toxicity; and recent technological innovations of building materials for greater resistance to UV radiation. These issues span a wide range of topics, including both harmful and beneficial effects of exposure to UV radiation, and complex interactions with climate change. While the Montreal Protocol has succeeded in preventing large reductions in stratospheric O3, future changes may occur due to a number of natural and anthropogenic factors. Thus, frequent assessments of potential environmental impacts are essential to ensure that policies remain based on the best available scientific knowledge.

Unique molecular signatures sustained in circulating monocytes and regulatory T cells in convalescent COVID-19 patients.

Over two years into the COVID-19 pandemic, the human immune response to SARS-CoV-2 during the active disease phase has been extensively studied. However, the long-term impact after recovery, which is critical to advance our understanding SARS-CoV-2 and COVID-19-associated long-term complications, remains largely unknown. Herein, we characterized single-cell profiles of circulating immune cells in the peripheral blood of 100 patients, including convalescent COVID-19 and sero-negative controls. Flow cytometry analyses revealed reduced frequencies of both short-lived monocytes and long-lived regulatory T (Treg) cells within the patients who have recovered from severe COVID-19. sc-RNA seq analysis identifies seven heterogeneous clusters of monocytes and nine Treg clusters featuring distinct molecular signatures in association with COVID-19 severity. Asymptomatic patients contain the most abundant clusters of monocytes and Tregs expressing high CD74 or IFN-responsive genes. In contrast, the patients recovered from a severe disease have shown two dominant inflammatory monocyte clusters featuring S100 family genes: one monocyte cluster of S100A8 & A9 coupled with high HLA-I and another cluster of S100A4 & A6 with high HLA-II genes, a specific non-classical monocyte cluster with distinct IFITM family genes, as well as a unique TGF-ß high Treg Cluster. The outpatients and seronegative controls share most of the monocyte and Treg clusters patterns with high expression of HLA genes. Surprisingly, while presumably short-lived monocytes appear to have sustained alterations over 4 months, the decreased frequencies of long-lived Tregs (high HLA-DRA and S100A6) in the outpatients restore over the tested convalescent time (≥ 4 months). Collectively, our study identifies sustained and dynamically altered monocytes and Treg clusters with distinct molecular signatures after recovery, associated with COVID-19 severity.

Linkages between COVID-19, solar UV radiation, and the Montreal Protocol.

There are several connections between coronavirus disease 2019 (COVID-19), solar UV radiation, and the Montreal Protocol. Exposure to ambient solar UV radiation inactivates SARS-CoV-2, the virus responsible for COVID-19. An action spectrum describing the wavelength dependence of the inactivation of SARS-CoV-2 by UV and visible radiation has recently been published. In contrast to action spectra that have been assumed in the past for estimating the effect of UV radiation on SARS-CoV-2, the new action spectrum has a large sensitivity in the UV-A (315-400 nm) range. If this "UV-A tail" is correct, solar UV radiation could be much more efficient in inactivating the virus responsible for COVID-19 than previously thought. Furthermore, the sensitivity of inactivation rates to the total column ozone would be reduced because ozone absorbs only a small amount of UV-A radiation. Using solar simulators, the times for inactivating SARS-CoV-2 have been determined by several groups; however, many measurements are affected by poorly defined experimental setups. The most reliable data suggest that 90% of viral particles embedded in saliva are inactivated within ~ 7 min by solar radiation for a solar zenith angle (SZA) of 16.5° and within ~ 13 min for a SZA of 63.4°. Slightly longer inactivation times were found for aerosolised virus particles. These times can become considerably longer during cloudy conditions or if virus particles are shielded from solar radiation. Many publications have provided evidence of an inverse relationship between ambient solar UV radiation and the incidence or severity of COVID-19, but the reasons for these negative correlations have not been unambiguously identified and could also be explained by confounders, such as ambient temperature, humidity, visible radiation, daylength, temporal changes in risk and disease management, and the proximity of people to other people. Meta-analyses of observational studies indicate inverse associations between serum 25-hydroxy vitamin D (25(OH)D) concentration and the risk of SARS-CoV-2 positivity or severity of COVID-19, although the quality of these studies is largely low. Mendelian randomisation studies have not found statistically significant evidence of a causal effect of 25(OH)D concentration on COVID-19 susceptibility or severity, but a potential link between vitamin D status and disease severity cannot be excluded as some randomised trials suggest that vitamin D supplementation is beneficial for people admitted to a hospital. Several studies indicate significant positive associations between air pollution and COVID-19 incidence and fatality rates. Conversely, well-established cohort studies indicate no association between long-term exposure to air pollution and infection with SARS-CoV-2. By limiting increases in UV radiation, the Montreal Protocol has also suppressed the inactivation rates of pathogens exposed to UV radiation. However, there is insufficient evidence to conclude that the expected larger inactivation rates without the Montreal Protocol would have had tangible consequences on the progress of the COVID-19 pandemic.

The effects of exposure to solar radiation on human health.

This assessment by the Environmental Effects Assessment Panel (EEAP) of the Montreal Protocol under the United Nations Environment Programme (UNEP) evaluates the effects of ultraviolet (UV) radiation on human health within the context of the Montreal Protocol and its Amendments. We assess work published since our last comprehensive assessment in 2018. Over the last four years gains have been made in knowledge of the links between sun exposure and health outcomes, mechanisms, and estimates of disease burden, including economic impacts. Of particular note, there is new information about the way in which exposure to UV radiation modulates the immune system, causing both harms and benefits for health. The burden of skin cancer remains high, with many lives lost to melanoma and many more people treated for keratinocyte cancer, but it has been estimated that the Montreal Protocol will prevent 11 million cases of melanoma and 432 million cases of keratinocyte cancer that would otherwise have occurred in the United States in people born between 1890 and 2100. While the incidence of skin cancer continues to rise, rates have stabilised in younger populations in some countries. Mortality has also plateaued, partly due to the use of systemic therapies for advanced disease. However, these therapies are very expensive, contributing to the extremely high economic burden of skin cancer, and emphasising the importance and comparative cost-effectiveness of prevention. Photodermatoses, inflammatory skin conditions induced by exposure to UV radiation, can have a marked detrimental impact on the quality of life of sufferers. More information is emerging about their potential link with commonly used drugs, particularly anti-hypertensives. The eyes are also harmed by over-exposure to UV radiation. The incidence of cataract and pterygium is continuing to rise, and there is now evidence of a link between intraocular melanoma and sun exposure. It has been estimated that the Montreal Protocol will prevent 63 million cases of cataract that would otherwise have occurred in the United States in people born between 1890 and 2100. Despite the clearly established harms, exposure to UV radiation also has benefits for human health. While the best recognised benefit is production of vitamin D, beneficial effects mediated by factors other than vitamin D are emerging. For both sun exposure and vitamin D, there is increasingly convincing evidence of a positive role in diseases related to immune function, including both autoimmune diseases and infection. With its influence on the intensity of UV radiation and global warming, the Montreal Protocol has, and will have, both direct and indirect effects on human health, potentially changing the balance of the risks and benefits of spending time outdoors.

Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change: UNEP Environmental Effects Assessment Panel, Update 2021.

The Environmental Effects Assessment Panel of the Montreal Protocol under the United Nations Environment Programme evaluates effects on the environment and human health that arise from changes in the stratospheric ozone layer and concomitant variations in ultraviolet (UV) radiation at the Earth's surface. The current update is based on scientific advances that have accumulated since our last assessment (Photochem and Photobiol Sci 20(1):1-67, 2021). We also discuss how climate change affects stratospheric ozone depletion and ultraviolet radiation, and how stratospheric ozone depletion affects climate change. The resulting interlinking effects of stratospheric ozone depletion, UV radiation, and climate change are assessed in terms of air quality, carbon sinks, ecosystems, human health, and natural and synthetic materials. We further highlight potential impacts on the biosphere from extreme climate events that are occurring with increasing frequency as a consequence of climate change. These and other interactive effects are examined with respect to the benefits that the Montreal Protocol and its Amendments are providing to life on Earth by controlling the production of various substances that contribute to both stratospheric ozone depletion and climate change.

A decision support tool for the detection of pancreatic cancer in general practice: A modified Delphi consensus.

BACKGROUND/OBJECTIVES: Diagnosis of pancreatic cancer is often delayed, contributing to patient and family distress and leading to worse survival. We aimed to develop a decision support tool to support primary care providers to identify patients that should undergo investigations for pancreatic cancer, and to recommend initial diagnostic pathways. METHODS: A modified Delphi process, including a series of three surveys, was undertaken to ascertain clinical expert opinion on which combinations of signs, symptoms and risk factors should be included in a tool for the early identification of pancreatic cancer. A group of clinical specialists finalised the development of the tool during a focus group meeting. RESULTS: The tool presents individual or combinations of signs, symptoms, and risk factors in three tiers which direct the urgency of investigation. Tier 1 includes 5 clinical presentation and risk factors clusters that indicate the need for urgent investigation of the pancreas. A further five clusters are included as Tier 2 aiming to elimate other causes and reduce the time to investigating the pancreas. Tier 3 includes a list of non-specific signs, symptoms and risk factors that indicate the need to consider pancreatic cancer as a potential diagnosis, but without specific recommendations for investigation. CONCLUSIONS: Prospective validation studies are now required prior to implementation in the primary care setting. Implementation into primary care practice and as an educational resource may facilitate rapid diagnosis and improve outcomes such as distress and survival.

Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change: UNEP Environmental Effects Assessment Panel, Update 2020.

This assessment by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) provides the latest scientific update since our most recent comprehensive assessment (Photochemical and Photobiological Sciences, 2019, 18, 595-828). The interactive effects between the stratospheric ozone layer, solar ultraviolet (UV) radiation, and climate change are presented within the framework of the Montreal Protocol and the United Nations Sustainable Development Goals. We address how these global environmental changes affect the atmosphere and air quality; human health; terrestrial and aquatic ecosystems; biogeochemical cycles; and materials used in outdoor construction, solar energy technologies, and fabrics. In many cases, there is a growing influence from changes in seasonality and extreme events due to climate change. Additionally, we assess the transmission and environmental effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the COVID-19 pandemic, in the context of linkages with solar UV radiation and the Montreal Protocol.

Clinical utility of skin cancer and melanoma risk scores for population screening: TRoPICS study.

BACKGROUND: Screening for skin cancer can be cost-effective if focused on high-risk groups. Risk prediction tools have been developed for keratinocyte cancers and melanoma to optimize advice and management. However, few have been validated in a clinical setting over the past few years. OBJECTIVES: To assess the clinical utility of risk assessment tools to identify individuals with prevalent skin cancers in a volunteer-based screening clinic. METHODS: Participants were adults presenting for a skin check at a volunteer-based skin cancer screening facility. We used previously published tools, based on questionnaire responses, to predict melanoma and keratinocyte cancers [KCs; basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] and classified each participant into one of five risk categories. Participants subsequently underwent a full skin examination by a dermatologist. All suspicious lesions were biopsied, and all cancers were histopathologically confirmed. RESULTS: Of 789 people who presented to the clinic, 507 (64%) consented to the study. Twenty-two BCCs, 19 SCCs and eight melanomas were diagnosed. The proportion of keratinocyte cancers diagnosed increased according to risk category from <1% in the lowest to 24% in the highest risk category (P < 0.001). Subtype analysis revealed similar proportionate increases in BCC or SCC prevalence according to risk category. However, a similar proportion of melanoma cases were detected in the low-risk and high-risk groups. CONCLUSION: The risk prediction model for keratinocyte cancers can reliably identify individuals with a significant skin cancer burden prior to a skin examination in the community setting. The prediction tool for melanoma needs to be tested in a larger sample exposed to a wider range of environmental risk factors.

Utilizing IoT to design a relief supply chain network for the SARS-COV-2 pandemic.

The current universally challenging SARS-COV-2 pandemic has transcended all the social, logical, economic, and mortal boundaries regarding global operations. Although myriad global societies tried to address this issue, most of the employed efforts seem superficial and failed to deal with the problem, especially in the healthcare sector. On the other hand, the Internet of Things (IoT) has enabled healthcare system for both better understanding of the patient's condition and appropriate monitoring in a remote fashion. However, there has always been a gap for utilizing this approach on the healthcare system especially in agitated condition of the pandemics. Therefore, in this study, we develop two innovative approaches to design a relief supply chain network is by using IoT to address multiple suspected cases during a pandemic like the SARS-COV-2 outbreak. The first approach (prioritizing approach) minimizes the maximum ambulances response time, while the second approach (allocating approach) minimizes the total critical response time. Each approach is validated and investigated utilizing several test problems and a real case in Iran as well. A set of efficient meta-heuristics and hybrid ones is developed to optimize the proposed models. The proposed approaches have shown their versatility in various harsh SARS-COV-2 pandemic situations being dealt with by managers. Finally, we compare the two proposed approaches in terms of response time and route optimization using a real case study in Iran. Implementing the proposed IoT-based methodology in three consecutive weeks, the results showed 35.54% decrease in the number of confirmed cases.

Does polygenic risk influence associations between sun exposure and melanoma? A prospective cohort analysis.

BACKGROUND: Melanoma develops as the result of complex interactions between sun exposure and genetic factors. However, data on these interactions from prospective studies are scant. OBJECTIVES: To quantify the association between ambient and personal ultraviolet exposure and incident melanoma in a large population-based prospective study of men and women residing in a setting of high ambient ultraviolet radiation, and to examine potential gene-environment interactions. METHODS: Data were obtained from the QSkin Sun and Health Study, a prospective cohort study of men and women aged 40-69 years, randomly sampled from the Queensland population in 2011. Participants were genotyped and assessed for ultraviolet exposure. RESULTS: Among participants with genetic data (n = 15 373), 420 (2·7%) developed cutaneous melanoma (173 invasive, 247 in situ) during a median follow-up time of 4·4 years. Country of birth, age at migration, having > 50 sunburns in childhood or adolescence, and a history of keratinocyte cancer or actinic lesions were significantly associated with melanoma risk. CONCLUSIONS: An interaction with polygenic risk was suggested: among people at low polygenic risk, markers of cumulative sun exposure (as measured by actinic damage) were associated with melanoma. In contrast, among people at high polygenic risk, markers of high-level early-life ambient exposure (as measured by place of birth) were associated with melanoma (hazard ratio for born in Australia vs. overseas 3·16, 95% confidence interval 1·39-7·22). These findings suggest interactions between genotype and environment that are consistent with divergent pathways for melanoma development. What's already known about this topic? The relationship between sun exposure and melanoma is complex, and exposure effects are highly modified by host factors and behaviours. The role of genotype on the relationship between ultraviolet radiation exposure and melanoma risk is poorly understood. What does this study add? We found that country of birth, age at migration, sunburns in childhood or adolescence, and history of keratinocyte cancer or actinic lesions were significantly associated with melanoma risk, while other measures of continuous or more intermittent patterns of sun exposure were not. We found evidence for gene-environment interactions that are consistent with divergent pathways for melanoma development. Linked Comment: Cust. Br J Dermatol 2020; 183:205-206. Plain language summary available online.

Environmental effects of stratospheric ozone depletion, UV radiation and interactions with climate change: UNEP Environmental Effects Assessment Panel, update 2019.

This assessment, by the United Nations Environment Programme (UNEP) Environmental Effects Assessment Panel (EEAP), one of three Panels informing the Parties to the Montreal Protocol, provides an update, since our previous extensive assessment (Photochem. Photobiol. Sci., 2019, 18, 595-828), of recent findings of current and projected interactive environmental effects of ultraviolet (UV) radiation, stratospheric ozone, and climate change. These effects include those on human health, air quality, terrestrial and aquatic ecosystems, biogeochemical cycles, and materials used in construction and other services. The present update evaluates further evidence of the consequences of human activity on climate change that are altering the exposure of organisms and ecosystems to UV radiation. This in turn reveals the interactive effects of many climate change factors with UV radiation that have implications for the atmosphere, feedbacks, contaminant fate and transport, organismal responses, and many outdoor materials including plastics, wood, and fabrics. The universal ratification of the Montreal Protocol, signed by 197 countries, has led to the regulation and phase-out of chemicals that deplete the stratospheric ozone layer. Although this treaty has had unprecedented success in protecting the ozone layer, and hence all life on Earth from damaging UV radiation, it is also making a substantial contribution to reducing climate warming because many of the chemicals under this treaty are greenhouse gases.

Aspirin and nonsteroidal anti-inflammatory drug use and keratinocyte cancers: a large population-based cohort study of skin cancer in Australia.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been postulated as chemopreventive agents for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), but findings from observational studies have been inconsistent, and clinical trial data are scant. OBJECTIVES: To examine the association between aspirin and NSAID (nonaspirin) use and the risk of BCC and SCC in a large cohort specifically designed for skin cancer outcomes. METHODS: We used data from the QSkin Study, a prospective cohort of 43 764 residents of Queensland, Australia (34 630 were included in this study and 23 581 were used in our primary analyses). We used Cox proportional hazards models to estimate the hazard ratios (HRs) between self-reported aspirin and NSAID use 1 year prior to study baseline and the first histologically confirmed BCC or SCC for high-risk (history of skin cancer excisions or more than five actinic lesions treated) and average-to-low-risk participants (no history of skin cancer excision and at most five actinic lesions treated). RESULTS: After a median of 3 years of follow-up, 3421 participants developed BCC and 1470 SCC (2288 BCC and 932 SCC with complete covariate information). Among the high-risk group (1826 BCC and 796 SCC), compared with never use, frequent (at least weekly) NSAID use was associated with reduced risk of BCC (HR 0·84, 95% confidence interval 0·71-0.99) but not SCC. Aspirin use was associated with reduced risk of SCC (HR 0·77, 95% confidence interval 0·64-0·93) only among infrequent (less than weekly) users and was not associated with BCC. We observed no association between NSAID or aspirin use and the risk of BCC or SCC among average-to-low-risk participants. CONCLUSIONS: While some weakly inverse associations were observed between prior use of aspirin or NSAIDs and skin cancer, the inconsistent patterns of associations do not provide convincing evidence that these medications reduce subsequent skin cancer risk. Further data on doses, duration and long-term follow-up may help us to comprehend the cumulative dose effect.

The effect of sunscreen on vitamin D: a review.

BACKGROUND: Sunscreen use can prevent skin cancer, but there are concerns that it may increase the risk of vitamin D deficiency. OBJECTIVES: We aimed to review the literature to investigate associations between sunscreen use and vitamin D3 or 25 hydroxyvitamin D [25(OH)D] concentration. METHODS: We systematically reviewed the literature following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. We identified manuscripts published in English between 1970 and 21 November 2017. Eligible studies were experimental [using an artificial ultraviolet radiation (UVR) source], field trials or observational studies. The results of each of the experimental studies and field trials are described in detail. Two authors extracted information from observational studies, and applied quality scoring criteria that were developed specifically for this question. These have been synthesized qualitatively. RESULTS: We included four experimental studies, three field trials (two were randomized controlled trials) and 69 observational studies. In the experimental studies sunscreen use considerably abrogated the vitamin D3 or 25(OH)D production induced by exposure to artificially generated UVR. The randomized controlled field trials found no effect of daily sunscreen application, but the sunscreens used had moderate protection [sun protection factor SPF) ~16]. The observational studies mostly found no association or that self-reported sunscreen use was associated with higher 25(OH)D concentration. CONCLUSIONS: There is little evidence that sunscreen decreases 25(OH)D concentration when used in real-life settings, suggesting that concerns about vitamin D should not negate skin cancer prevention advice. However, there have been no trials of the high-SPF sunscreens that are now widely recommended. What's already known about this topic? Previous experimental studies suggest that sunscreen can block vitamin D production in the skin but use artificially generated ultraviolet radiation with a spectral output unlike that seen in terrestrial sunlight. Nonsystematic reviews of observational studies suggest that use in real life does not cause vitamin D deficiency. What does this study add? This study systematically reviewed all experimental studies, field trials and observational studies for the first time. While the experimental studies support the theoretical risk that sunscreen use may affect vitamin D, the weight of evidence from field trials and observational studies suggests that the risk is low. We highlight the lack of adequate evidence regarding use of the very high sun protection factor sunscreens that are now recommended and widely used.

Human health in relation to exposure to solar ultraviolet radiation under changing stratospheric ozone and climate.

The Montreal Protocol has limited increases in the UV-B (280-315 nm) radiation reaching the Earth's surface as a result of depletion of stratospheric ozone. Nevertheless, the incidence of skin cancers continues to increase in most light-skinned populations, probably due mainly to risky sun exposure behaviour. In locations with strong sun protection programs of long duration, incidence is now reducing in younger age groups. Changes in the epidemiology of UV-induced eye diseases are less clear, due to a lack of data. Exposure to UV radiation plays a role in the development of cataracts, pterygium and possibly age-related macular degeneration; these are major causes of visual impairment world-wide. Photodermatoses and phototoxic reactions to drugs are not uncommon; management of the latter includes recognition of the risks by the prescribing physician. Exposure to UV radiation has benefits for health through the production of vitamin D in the skin and modulation of immune function. The latter has benefits for skin diseases such as psoriasis and possibly for systemic autoimmune diseases such as multiple sclerosis. The health risks of sun exposure can be mitigated through appropriate sun protection, such as clothing with both good UV-blocking characteristics and adequate skin coverage, sunglasses, shade, and sunscreen. New sunscreen preparations provide protection against a broader spectrum of solar radiation, but it is not clear that this has benefits for health. Gaps in knowledge make it difficult to derive evidence-based sun protection advice that balances the risks and benefits of sun exposure.

Environmental effects of ozone depletion, UV radiation and interactions with climate change: UNEP Environmental Effects Assessment Panel, update 2017.

The Environmental Effects Assessment Panel (EEAP) is one of three Panels of experts that inform the Parties to the Montreal Protocol. The EEAP focuses on the effects of UV radiation on human health, terrestrial and aquatic ecosystems, air quality, and materials, as well as on the interactive effects of UV radiation and global climate change. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than previously held. Because of the Montreal Protocol, there are now indications of the beginnings of a recovery of stratospheric ozone, although the time required to reach levels like those before the 1960s is still uncertain, particularly as the effects of stratospheric ozone on climate change and vice versa, are not yet fully understood. Some regions will likely receive enhanced levels of UV radiation, while other areas will likely experience a reduction in UV radiation as ozone- and climate-driven changes affect the amounts of UV radiation reaching the Earth's surface. Like the other Panels, the EEAP produces detailed Quadrennial Reports every four years; the most recent was published as a series of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1-184). In the years in between, the EEAP produces less detailed and shorter Update Reports of recent and relevant scientific findings. The most recent of these was for 2016 (Photochem. Photobiol. Sci., 2017, 16, 107-145). The present 2017 Update Report assesses some of the highlights and new insights about the interactive nature of the direct and indirect effects of UV radiation, atmospheric processes, and climate change. A full 2018 Quadrennial Assessment, will be made available in 2018/2019.

Dietary acrylamide and the risk of pancreatic cancer in the International Pancreatic Cancer Case-Control Consortium (PanC4).

Background: Occupational exposure to acrylamide was associated with excess mortality from pancreatic cancer, though in the absence of dose-risk relationship. Few epidemiological studies have examined the association between acrylamide from diet and pancreatic cancer risk. Patients and methods: We considered this issue in a combined set of 1975 cases of pancreatic cancer and 4239 controls enrolled in six studies of the Pancreatic Cancer Case-Control Consortium (PanC4). We calculated pooled odds ratios (ORs) and their 95% confidence intervals (CI) by estimating study-specific ORs through multivariate unconditional logistic regression models and pooling the obtained estimates using random-effects models. Results: Compared with the lowest level of estimated dietary acrylamide intake, the pooled ORs were 0.97 (95% CI, 0.79-1.19) for the second, 0.91 (95% CI, 0.71-1.16) for the third, and 0.92 (95% CI, 0.66-1.28) for the fourth (highest) quartile of intake. For an increase of 10 µg/day of acrylamide intake, the pooled OR was 0.96 (95% CI, 0.87-1.06), with heterogeneity between estimates (I2 = 67%). Results were similar across various subgroups, and were confirmed when using a one-stage modelling approach. Conclusions: This PanC4 pooled-analysis found no association between dietary acrylamide and pancreatic cancer.

Successful Bridge-to-Transplant of Functionally Univentricular Patients With a Modified Continuous-Flow Ventricular Assist Device.

A continuous flow extracorporeal ventricular assist device (VAD) was modified to support functionally univentricular infants and children awaiting heart transplantation. A centrifugal VAD, designed to flow from 1.5 to 8 L/min, was used as a bridge-to-transplant in four patients with functionally univentricular circulation. A variable restrictive recirculation shunt permitted lower flow ranges in small patients. In hypoxic patients, an oxygenator was incorporated into the circuit. From 2012 to 2015, the modified VAD was placed in four patients with Glenn physiology. Age ranged from 0.97 to 6.98 years (median = 2.2 yrs). Body surface area ranged from 0.41 to 0.84 m2 (median = 0.54 m2 ). One patient was on extracorporeal membrane oxygenation prior to VAD. A recirculation shunt was used in three patients. Three patients required temporary use of an oxygenator for 4, 10, and 27 days. Median time on the VAD was 32.3 days (range = 23-43 days). A decrease in the cavopulmonary pressure was noted in all patients, as was a fall in the B-type natriuretic peptide. Three patients survived transplant and were discharged at 28-82 days post-transplantation. One patient died after 35 days of support. Two patients experienced major bleeding events. Two patients experienced cerebrovascular accidents, one major and one minor. The centrifugal VAD successfully supported palliated functionally univentricular patients awaiting heart transplantation. The modified recirculation shunt facilitated the successful support of patients in whom optimal flows were substantially lower than that recommended by the manufacturer. The continuous-flow VAD effectively decompressed the cavopulmonary system. The design allowed placement of an in-line oxygenator in hypoxic patients. Further investigation is required to decrease the thromboembolic events, and associated morbidity, in patients supported with this device.

Determinants of survival and attempted resection in patients with non-metastatic pancreatic cancer: An Australian population-based study.

BACKGROUND: There are indications that pancreatic cancer survival may differ according to sociodemographic factors, such as residential location. This may be due to differential access to curative resection. Understanding factors associated with the decision to offer a resection might enable strategies to increase the proportion of patients undergoing potentially curative surgery. METHODS: Data were extracted from medical records and cancer registries for patients diagnosed with pancreatic cancer between July 2009 and June 2011, living in one of two Australian states. Among patients clinically staged with non-metastatic disease we examined factors associated with survival using Cox proportional hazards models. To investigate survival differences we examined determinants of: 1) attempted surgical resection overall; 2) whether patients with locally advanced disease were classified as having resectable disease; and 3) attempted resection among those considered resectable. RESULTS: Data were collected for 786 eligible patients. Disease was considered locally advanced for 561 (71%) patients, 510 (65%) were classified as having potentially resectable disease and 365 (72%) of these had an attempted resection. Along with age, comorbidities and tumour stage, increasing remoteness of residence was associated with poorer survival. Remoteness of residence and review by a hepatobiliary surgeon were factors influencing the decision to offer surgery. CONCLUSIONS: This study indicated disparity in survival dependent on patients' residential location and access to a specialist hepatobiliary surgeon. Accurate clinical staging is a critical element in assessing surgical resectability and it is therefore crucial that all patients have access to specialised clinical services.

Vitamin D and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium.

BACKGROUND: The potential role of vitamin D in the aetiology of pancreatic cancer is unclear, with recent studies suggesting both positive and negative associations. PATIENTS AND METHODS: We used data from nine case-control studies from the International Pancreatic Cancer Case-Control Consortium (PanC4) to examine associations between pancreatic cancer risk and dietary vitamin D intake. Study-specific odds ratios (ORs) were estimated using multivariable logistic regression, and ORs were then pooled using a random-effects model. From a subset of four studies, we also calculated pooled estimates of association for supplementary and total vitamin D intake. RESULTS: Risk of pancreatic cancer increased with dietary intake of vitamin D [per 100 international units (IU)/day: OR = 1.13, 95% confidence interval (CI) 1.07-1.19, P = 7.4 × 10(-6), P-heterogeneity = 0.52; ≥230 versus <110 IU/day: OR = 1.31, 95% CI 1.10-1.55, P = 2.4 × 10(-3), P-heterogeneity = 0.81], with the association possibly stronger in people with low retinol/vitamin A intake. CONCLUSION: Increased risk of pancreatic cancer was observed with higher levels of dietary vitamin D intake. Additional studies are required to determine whether or not our finding has a causal basis.