Intimate networks of care: Perceptions of intergenerational family care and experiences of ageing among Chinese midlife and older lesbians and gay men.

This article examines how lesbians and gay men imagine and build their 'intimate networks of care' and negotiate moral expectations towards intergenerational family care as they age. To date, little is known about the strength and complexities of different intimate ties or the role of intergenerational dynamics in shaping ageing sexual minority people's care needs and choices. Based on narrative interviews with ageing Chinese lesbians and gay men, the findings reveal their experiences of constantly juggling their ties with families of origin, moral values around intergenerational care and the urge to receive support from and offer support to chosen networks of people. Participants exercised agency in expanding their networks of care by building friendship and (online and offline) community networks for mutual care and support in later life. Nevertheless, as evidenced by the centrality of ageing with(out) children, and the moral obligation of caring for parents in participants' narratives, participants experienced tensions between enacting what was considered morally right/wrong and developing networks of care that were perceived as emotionally intimate. Linking relational sociology with the sociology of morality, we discuss the conceptual utility of 'intimate networks of care' for sociological theorising of the linkages between sexuality, care and relational lives.

Exposure to Violence in Social Unrest, Resilience, and Mental Health of Older People in Hong Kong.

OBJECTIVE: Older adults are prone to the negative effects of exposure to violence on their mental health. This study aimed to examine the impact of exposure to violence during social unrest and the role of resilience in the mental health of older people. DESIGN: A total of 1,203 people aged 65 years or older were randomly selected for a telephone survey using the random digit dialing numbering method in Hong Kong. MEASUREMENTS: A 13-item scale was developed to measure exposure to violence. The Chinese versions of the Connor-Davidson Resilience Scale and the Startle, Physiological Arousal, Anger, and Numbness scales for measuring mental health status were adopted in the survey. RESULTS: The results showed that the more frequently older people were exposed to information, the more negative mental health status they had. However, exposure to witnessing and experiencing violence was not significantly associated with mental health status. Older adults' level of resilience had a moderating effect between exposure to information and mental health, whereas the effect of exposure to information on mental health was stronger for respondents with lower resilience. CONCLUSION: This study showed that emotional problems caused by exposure to related information among older people should be properly addressed during massive social unrest and conflict. Their resilience capacity is an important moderating factor. Future interventions and support services should focus on enhancing the resilience of older people to better equip them with overcoming problems related to macro-social issues.

Experience of Chinese Recent Retirees on the Effects of Retirement on Healthy Ageing in Shenzhen and Hong Kong.

This study examined perspectives of recent retirees in Shenzhen and Hong Kong on how retirement influenced their healthy ageing. It investigated retirees' perceptions of healthy ageing and the ways in which healthy ageing connected with retirees' transition into retirement. A qualitative design with narrative interviews was used to interview twelve recent retirees in Shenzhen and thirteen in Hong Kong. The participants elaborated their perspectives on healthy ageing, which covered physical, mental, social, and financial domains. Retirees in both cities identified healthy ageing as maintaining an independent life and avoiding becoming a burden on family members. This study found that retirement declined physical health (in parallel with raised awareness of health promotion), posed both negative and positive influences on mental health, and shrank peripheral social networks of retirees. In addition, regional social welfare systems have different impacts on retirees' financial security and social participation. Retirees in Hong Kong reported higher stress of financial security and a strong desire for labor participation. Migrant-local welfare gaps were documented by retirees in Shenzhen. This study suggested that retirement planning, establishing a multi-pillar retirement-protection system, and narrowing the welfare gap between migrants and local residents should be implemented to reinforce healthy ageing.

Back to the campus: Lifelong experience of older learners in a university setting.

This study focuses on older participants' experiences of and views on a lifelong learning program at the Hong Kong Polytechnic University in Hong Kong. As many third age adults tend not to have the opportunity to receive tertiary education when they were young, this program aims to fulfil their dream of studying at a university and boost their self-esteem and self-confidence. Using qualitative research methods, this research was conducted after the MiniU program (supported by the Institute of Active Aging of the Hong Kong Polytechnic University). Semi-structured interviews were conducted with 32 participants after the program. While participants had acquired knowledge and experience of university life from the Mini-U program, they also reported concerns and difficulties with participation including difficulties in memorizing course content and financial difficulties. The program has offered a unique opportunity for enhancing participants' interpersonal relationships and wellbeing. The research also further informs the development of creative lifelong learning programs aimed at improving the well-being of older people.

Reflexive Planning for Later Life: Minority Stress and Aging Challenges among Midlife Chinese Lesbians and Gay Men.

This study examines how Chinese lesbians and gay men make sense of the prospect of growing old and plan for later life in Hong Kong, where same-sex relationships are yet to be legally recognized. Drawing on in-depth narrative interviews, the results show that lesbians and gay men in midlife reported a range of previous, current, and anticipated challenges associated with the stigma attached to homosexuality. These, in turn, shaped their ways of perceiving and planning for later life. Three forms of reflexivity in response to minority stress and the prospect of aging were identified: coping with fears of aging alone, striving for self-mastery, and planning ahead with feelings of wariness. Participants' concerns and plans around aging demonstrated differing degrees of reflexivity, through which they attempted to navigate family norms and structural constraints and find ways to accumulate resources for later life. Meanwhile, their heightened sense of uncertainty and insecurity showed that their perceptions and experiences of aging were influenced by minority stress and material, familial, and socio-political circumstances. This article builds a constructive dialogue between sexuality and aging studies by unraveling both the aging insecurity and capacities for reflexive planning among an oft-neglected group of sexual minority people in midlife.

Exposure to socio-political unrest and wellbeing of older people in Hong Kong.

BACKGROUND: The social unrest in the second half of 2019 in Hong Kong came with conflicts, confrontations, and violence which affected almost everyone in the city. The destruction and disruption of the urban facilities have undoubtedly had a significant impact on the lives and mental well-being of the public, and the older people are even more vulnerable. This study examined the impacts of the social unrest on the wellbeing of older people, an area that was seldomly addressed in the public discourse and literature. METHODS: Narrative interviews were conducted to capture older people's lived experiences and ways of making sense of the unrest in Hong Kong. A total of 63 participants aged 60 and above was recruited through personal networks of the research team, and referrals by participants who took part in the interviews. Qualitative semi-structure interviews was conducted one on one via telephone. RESULTS: Thirty-three male and 30 female participants took part in the interview. The number of participants from different risk zones affected by political unrest was comparable. Three themes were generated. Participants experienced challenges during the social unrest, including disturbance to family and social life, reduced incomes which affect quality of life, and difficulties in socializing with friends and accessing medical services. The social unrest caused emotional disturbance, giving rise to feelings of panic, fear, insomnia, depression, annoyance, and anger. Participants reported different coping strategies, ranging from moving to other places, to avoiding going to risky areas and watching news. CONCLUSION: Social unrest brings emotional distress to older people. In many cases, older people cope with challenges in different ways, whether active or passive. Social workers and other professionals should give more support to older people to encourage them to overcome their difficulties. The stakeholders' awareness of the problem and mental health promotion is required to alleviate the multiple layers of negative impacts.

Molecular landscape of IDH-wild type, pTERT-wild type adult glioblastomas.

Telomerase reverse transcriptase (TERT) promoter (pTERT) mutation has often been described as a late event in gliomagenesis and it has been suggested as a prognostic biomarker in gliomas other than 1p19q codeleted tumors. However, the characteristics of isocitrate dehydrogenase (IDH) wild type (wt) (IDHwt), pTERTwt glioblastomas are not well known. We recruited 72 adult IDHwt, pTERTwt glioblastomas and performed methylation profiling, targeted sequencing, and fluorescence in situ hybridization (FISH) for TERT structural rearrangement and ALT (alternative lengthening of telomeres). There was no significant difference in overall survival (OS) between our cohort and a the Cancer Genome Atlas (TCGA) cohort of IDHwt, pTERT mutant (mut) glioblastomas, suggesting that pTERT mutation on its own is not a prognostic factor among IDHwt glioblastomas. Epigenetically, the tumors clustered into classic-like (11%), mesenchymal-like (32%), and LGm6-glioblastoma (GBM) (57%), the latter far exceeding the corresponding proportion seen in the TCGA cohort of IDHwt, pTERTmut glioblastomas. LGm6-GBM-clustered tumors were enriched for platelet derived growth factor receptor alpha (PDGFRA) amplification or mutation (p = 0.008), and contained far fewer epidermal growth factor receptor (EGFR) amplification (p < 0.01), 10p loss (p = 0.001) and 10q loss (p < 0.001) compared with cases not clustered to this group. LGm6-GBM cases predominantly showed ALT (p = 0.038). In the whole cohort, only 35% cases showed EGFR amplification and no case showed combined chromosome +7/-10. Since the cases were already pTERTwt, so the three molecular properties of EGFR amplification, +7/-10, and pTERT mutation may not cover all IDHwt glioblastomas. Instead, EGFR and PDGFRA amplifications covered 67% and together with their mutations covered 71% of cases of this cohort. Homozygous deletion of cyclin dependent kinase inhibitor 2A (CDKN2A)/B was associated with a worse OS (p = 0.031) and was an independent prognosticator in multivariate analysis (p = 0.032). In conclusion, adult IDHwt, pTERTwt glioblastomas show epigenetic clustering different from IDHwt, pTERTmut glioblastomas, and IDHwt glioblastomas which are pTERTwt may however not show EGFR amplification or +7/-10 in a significant proportion of cases. CDKN2A/B deletion is a poor prognostic biomarker in this group.

Prince Rupert's Drops: An analysis of fragmentation by thermal stresses and quench granulation of glass and bubbly glass.

When volcanic eruptions involve interaction with external water (hydrovolcanism), the result is an ash-rich and energetic volcanic plume, as illustrated dramatically by the January 2022 Tonga eruption. The origin of the high explosive energy of these events remains an important question. We investigate this question by studying Prince Rupert's Drops (PRDs)-tadpole-shaped glass beads formed by dripping molten glass into water-which have long fascinated materials scientists because the great strength of the head contrasts with the explosivity of the metastable interior when the tail is broken. We show that the fragment size distribution (FSD) produced by explosive fragmentation changes systematically with PRD fragmentation in air, water, and syrup. Most FSDs are fractal over much of the size range, scaling that can be explained by the repeated fracture bifurcation observed in three-dimensional images from microcomputed tomography. The shapes of constituent fragments are determined by their position within the original PRD, with platey fragments formed from the outer (compressive) shell and blocky fragments formed by fractures perpendicular to interior voids. When molten drops fail to form PRDs, the glass disintegrates by quench granulation, a process that produces fractal FSDs but with a larger median size than explosively generated fragments. Critically, adding bubbles to the molten glass prevents PRD formation and promotes quench granulation, suggesting that granulation is modulated by heterogeneous stress fields formed around the bubbles during sudden cooling and contraction. Together, these observations provide insight into glass fragmentation and potentially, processes operating during hydrovolcanism.

Family and Work Lives of Lesbians in China: Implications for the Adult Worker Model.

This article examines the ways in which lesbians explore opportunities and navigate constraints in their family and work lives in urban China. It not only reveals Chinese lesbians' difficulties in gaining equal access to the labour market and developing their desired family lives, but also discusses possible ways of enhancing the applicability of the adult worker model for sexual minority women. Previous research has indicated a shift from the male breadwinner model to the adult worker model, suggesting that both men and women are expected to join the labour market, and that women should not carry all the care responsibilities within the family. However, the model largely overlooks the interplay of gender and sexuality factors in shaping work and family lives. This article adopts a qualitative mixed-methods approach, including interviews with 20 Chinese lesbians and social media analysis, to examine lesbians' experiences of taking part in the family as adults and in the wider economy as workers. It shows how gender norms, heteronormativity, and policy intersect in generating obstacles for Chinese lesbians to thrive as respectable adult workers. This has important implications for attempts to improve the adult worker model to fit better with people's diverse work/family needs.

Virucidal activities of novel hand hygiene and surface disinfectant formulations containing EGCG-palmitates (EC16).

BACKGROUND: Non-toxic hand hygiene and surface disinfectant products with virucidal activity against alcohol-resistant nonenveloped norovirus are in urgent need. METHOD: Alcohol-based formulations were made with epigallocatechin-3-gallate-palmitate (EC16), an FDA accepted food additive. Based on in-house testing of formulations, 3 prototypes, PTV80 hand gel, PST70 surface disinfectant spray and PST70 surface disinfectant wipe, were selected from in-house tests for independent testing at GLP (good laboratory practice) laboratories according to EN 14476:2019 (hand gel), ASTM test method E1053-20 (spray), and ASTM E2362-15, E1053, and ASTM E2896-12 (wipe). RESULTS: The PTV80 hand gel prototype demonstrated a >99.999% reduction of murine norovirus S99 infectivity in 60 seconds. Carrier testing of the PST70 surface spray and surface wipe demonstrated reduction of feline calicivirus infectivity by >99.99% in 60 seconds. In addition, testing with human coronavirus and human herpes simplex virus demonstrated >99.99% efficacy in 60 seconds, consistent with broad spectrum virucidal activity. CONCLUSIONS: The novel non-toxic prototypes containing EC16 were found to be suitable for use in future hand sanitizer gel, surface disinfectant spray and wipe products against norovirus. Products based on these formulations could be used safely to help prevent and control norovirus and other emerging virus outbreaks, pending future studies.

Bactericidal and fungicidal activities of novel ProtecTeaV formulations - alcohol-based hand hygiene and surface disinfectant prototypes containing epigallocatechin-3-gallate-palmitate (EC16).

Objective: Currently used alcohol-based hand sanitizers and surgical hand rubs are not effective against alcohol-resistant microorganisms. We reported previously that nontoxic antioxidant food additive compounds derived from green tea polyphenols, particularly epigallocatechin-3-gallate-palmitate (EC16), are suitable in alcohol formulations to effectively inactivate nonenveloped viruses and bacterial spores. However, whether EC16 influences the bactericidal and fungicidal activity of alcohol is not clear. The objective of the current study was to determine the bactericidal and fungicidal activities of ProtecTeaV hand sanitizer and surface spray prototypes containing EC16. Methods: The prototypes were tested according to the guidelines from the Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA). Results: As expected, EC16 did not reduce the bactericidal and fungicidal activities of ethanol. The hand sanitizer gel formulation was equally effective as 70% ethanol and met the tested standard, and the surface spray prototype met the EPA performance standard. Conclusions: EC16 can be combined with ethanol without reducing antibacterial or antifungal activity, and the ProtecTeaV prototypes could be further developed into novel hand hygiene and surface disinfectant products with virucidal, bactericidal, fungicidal and sporicidal activities.

International Survey to Establish Prioritized Outcomes for Trials in People With Coronavirus Disease 2019.

OBJECTIVES: There are over 4,000 trials conducted in people with coronavirus disease 2019. However, the variability of outcomes and the omission of patient-centered outcomes may diminish the impact of these trials on decision-making. The aim of this study was to generate a consensus-based, prioritized list of outcomes for coronavirus disease 2019 trials. DESIGN: In an online survey conducted in English, Chinese, Italian, Portuguese, and Spanish languages, adults with coronavirus disease 2019, their family members, health professionals, and the general public rated the importance of outcomes using a 9-point Likert scale (7-9, critical importance) and completed a Best-Worst Scale to estimate relative importance. Participant comments were analyzed thematically. SETTING: International. SUBJECTS: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public, and health professionals (including clinicians, policy makers, regulators, funders, and researchers). INTERVENTIONS: None. MEASUREMENTS: None. MAIN RESULTS: In total, 9,289 participants from 111 countries (776 people with coronavirus disease 2019 or family members, 4,882 health professionals, and 3,631 members of the public) completed the survey. The four outcomes of highest priority for all three groups were: mortality, respiratory failure, pneumonia, and organ failure. Lung function, lung scarring, sepsis, shortness of breath, and oxygen level in the blood were common to the top 10 outcomes across all three groups (mean > 7.5, median ≥ 8, and > 70% of respondents rated the outcome as critically important). Patients/family members rated fatigue, anxiety, chest pain, muscle pain, gastrointestinal problems, and cardiovascular disease higher than health professionals. Four themes underpinned prioritization: fear of life-threatening, debilitating, and permanent consequences; addressing knowledge gaps; enabling preparedness and planning; and tolerable or infrequent outcomes. CONCLUSIONS: Life-threatening respiratory and other organ outcomes were consistently highly prioritized by all stakeholder groups. Patients/family members gave higher priority to many patient-reported outcomes compared with health professionals.

Core Outcomes Set for Trials in People With Coronavirus Disease 2019.

OBJECTIVES: The outcomes reported in trials in coronavirus disease 2019 are extremely heterogeneous and of uncertain patient relevance, limiting their applicability for clinical decision-making. The aim of this workshop was to establish a core outcomes set for trials in people with suspected or confirmed coronavirus disease 2019. DESIGN: Four international online multistakeholder consensus workshops were convened to discuss proposed core outcomes for trials in people with suspected or confirmed coronavirus disease 2019, informed by a survey involving 9,289 respondents from 111 countries. The transcripts were analyzed thematically. The workshop recommendations were used to finalize the core outcomes set. SETTING: International. SUBJECTS: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public and health professionals (including clinicians, policy makers, regulators, funders, researchers). INTERVENTIONS: None. MEASUREMENTS: None. MAIN RESULTS: Six themes were identified. "Responding to the critical and acute health crisis" reflected the immediate focus on saving lives and preventing life-threatening complications that underpinned the high prioritization of mortality, respiratory failure, and multiple organ failure. "Capturing different settings of care" highlighted the need to minimize the burden on hospitals and to acknowledge outcomes in community settings. "Encompassing the full trajectory and severity of disease" was addressing longer term impacts and the full spectrum of illness (e.g. shortness of breath and recovery). "Distinguishing overlap, correlation and collinearity" meant recognizing that symptoms such as shortness of breath had distinct value and minimizing overlap (e.g. lung function and pneumonia were on the continuum toward respiratory failure). "Recognizing adverse events" refers to the potential harms of new and evolving interventions. "Being cognizant of family and psychosocial wellbeing" reflected the pervasive impacts of coronavirus disease 2019. CONCLUSIONS: Mortality, respiratory failure, multiple organ failure, shortness of breath, and recovery are critically important outcomes to be consistently reported in coronavirus disease 2019 trials.

BVLOS UAS Operations in Highly-Turbulent Volcanic Plumes.

Long-range, high-altitude Unoccupied Aerial System (UAS) operations now enable in-situ measurements of volcanic gas chemistry at globally-significant active volcanoes. However, the extreme environments encountered within volcanic plumes present significant challenges for both air frame development and in-flight control. As part of a multi-disciplinary field deployment in May 2019, we flew fixed wing UAS Beyond Visual Line of Sight (BVLOS) over Manam volcano, Papua New Guinea, to measure real-time gas concentrations within the volcanic plume. By integrating aerial gas measurements with ground- and satellite-based sensors, our aim was to collect data that would constrain the emission rate of environmentally-important volcanic gases, such as carbon dioxide, whilst providing critical insight into the state of the subsurface volcanic system. Here, we present a detailed analysis of three BVLOS flights into the plume of Manam volcano and discuss the challenges involved in operating in highly turbulent volcanic plumes. Specifically, we report a detailed description of the system, including ground and air components, and flight plans. We present logged flight data for two successful flights to evaluate the aircraft performance under the atmospheric conditions experienced during plume traverses. Further, by reconstructing the sequence of events that led to the failure of the third flight, we identify a number of lessons learned and propose appropriate recommendations to reduce risk in future flight operations.

Reticulon and CLIMP-63 regulate nanodomain organization of peripheral ER tubules.

The endoplasmic reticulum (ER) is an expansive, membrane-enclosed organelle composed of smooth peripheral tubules and rough, ribosome-studded central ER sheets whose morphology is determined, in part, by the ER-shaping proteins, reticulon (RTN) and cytoskeleton-linking membrane protein 63 (CLIMP-63), respectively. Here, stimulated emission depletion (STED) super-resolution microscopy shows that reticulon4a (RTN4a) and CLIMP-63 also regulate the organization and dynamics of peripheral ER tubule nanodomains. STED imaging shows that lumenal ER monomeric oxidizing environment-optimized green fluorescent protein (ERmoxGFP), membrane Sec61ßGFP, knock-in calreticulin-GFP, and antibody-labeled ER-resident proteins calnexin and derlin-1 are all localized to periodic puncta along the length of peripheral ER tubules that are not readily observable by diffraction limited confocal microscopy. RTN4a segregates away from and restricts lumenal blob length, while CLIMP-63 associates with and increases lumenal blob length. RTN4a and CLIMP-63 also regulate the nanodomain distribution of ER-resident proteins, being required for the preferential segregation of calnexin and derlin-1 puncta away from lumenal ERmoxGFP blobs. High-speed (40 ms/frame) live cell STED imaging shows that RTN4a and CLIMP-63 regulate dynamic nanoscale lumenal compartmentalization along peripheral ER tubules. RTN4a enhances and CLIMP-63 disrupts the local accumulation of lumenal ERmoxGFP at spatially defined sites along ER tubules. The ER-shaping proteins RTN and CLIMP-63 therefore regulate lumenal ER nanodomain heterogeneity, interaction with ER-resident proteins, and dynamics in peripheral ER tubules.

The timing and widespread effects of the largest Holocene volcanic eruption in Antarctica.

The caldera collapse of Deception Island Volcano, Antarctica, was comparable in scale to some of the largest eruptions on Earth over the last several millennia. Despite its magnitude and potential for far-reaching environmental effects, the age of this event has never been established, with estimates ranging from the late Pleistocene to 3370 years before present. Here we analyse nearby lake sediments in which we identify a singular event produced by Deception Island's caldera collapse that occurred 3980 ± 125 calibrated years before present. The erupted tephra record the distinct geochemical composition of ejecta from the caldera-forming eruption, whilst an extreme seismic episode is recorded by lake sediments immediately overlying the collapse tephra. The newly constrained caldera collapse is now the largest volcanic eruption confirmed in Antarctica during the Holocene. An examination of palaeorecords reveals evidence in marine and lacustrine sediments for contemporaneous seismicity around the Antarctic Peninsula; synchronous glaciochemical volcanic signatures also record the eruption in ice cores spread around Antarctica, reaching >4600 km from source. The widespread footprint suggests that this eruption would have had significant climatic and ecological effects across a vast area of the south polar region.

A Quantitative Analysis of the Relationship Between Radiation Therapy Use and Travel Time.

PURPOSE: To model and quantify the relationship between radiation therapy (RT) use and travel time to RT services. METHODS AND MATERIALS: Population-based registries and databases were used to identify both incident cancer patient and patients receiving RT within 1 year of diagnosis (RT1y) in British Columbia, Canada, between 1992 and 2011. The effects of age, gender, diagnosis year, income, prevailing wait time, and travel duration for RT on RT1y were assessed. Significant factors from univariate analyses were included in a multivariable logistic regression model. The shape of the travel time-RT1y curve was represented by generalized additive and segmented regression models. Analyses were conducted for breast, lung, and genitourinary cancer separately and for all cancer sites combined. RESULTS: After adjustment for age, gender, diagnosis year, income, and prevailing wait times, increasing travel time to the closest RT facility had a negative impact RT1y. The shape of the travel time-RT1y curve varied with cancer type. For breast cancer, the odds of RT1y were constant for the first 2 driving hours and decreased at 17% per hour thereafter. For lung cancer, the odds of RT1y decreased by 16% after 20 minutes and then decreased at 6% per hour. Genitourinary cancer RT1y was relatively independent of travel time. For all cancer sites combined, the odds of RT1y were constant within the first 2 driving hours and decreased at 7% per hour thereafter. CONCLUSIONS: Travel time to receive RT has a different impact on RT1y for different tumor sites. The results provide evidence-based insights for the configuration of catchment areas for new and existing cancer centers providing RT.

Loss of autophagy causes a synthetic lethal deficiency in DNA repair.

(Macro)autophagy delivers cellular constituents to lysosomes for degradation. Although a cytoplasmic process, autophagy-deficient cells accumulate genomic damage, but an explanation for this effect is currently unclear. We report here that inhibition of autophagy causes elevated proteasomal activity leading to enhanced degradation of checkpoint kinase 1 (Chk1), a pivotal factor for the error-free DNA repair process, homologous recombination (HR). We show that loss of autophagy critically impairs HR and that autophagy-deficient cells accrue micronuclei and sub-G1 DNA, indicators of diminished genomic integrity. Moreover, due to impaired HR, autophagy-deficient cells are hyperdependent on nonhomologous end joining (NHEJ) for repair of DNA double-strand breaks. Consequently, inhibition of NHEJ following DNA damage in the absence of autophagy results in persistence of genomic lesions and rapid cell death. Because autophagy deficiency occurs in several diseases, these findings constitute an important link between autophagy and DNA repair and highlight a synthetic lethal strategy to kill autophagy-deficient cells.

Optimal location of radiation therapy centers with respect to geographic access.

PURPOSE: To develop a framework with which to evaluate locations of radiation therapy (RT) centers in a region based on geographic access. METHODS AND MATERIALS: Patient records were obtained for all external beam radiation therapy started in 2011 for the province of British Columbia, Canada. Two metrics of geographic access were defined. The primary analysis was percentage of patients (coverage) within a 90-minute drive from an RT center (C90), and the secondary analysis was the average drive time (ADT) to an RT center. An integer programming model was developed to determine optimal center locations, catchment areas, and capacity required under different scenarios. RESULTS: Records consisted of 11,096 courses of radiation corresponding to 161,616 fractions. Baseline geographic access was estimated at 102.5 minutes ADT (each way, per fraction) and 75.9% C90. Adding 2 and 3 new centers increased C90 to 88% and 92%, respectively, and decreased ADT by between 43% and 61%, respectively. A scenario in which RT was provided in every potential location that could support at least 1 fully utilized linear accelerator resulted in 35.3 minutes' ADT and 93.6% C90. CONCLUSIONS: The proposed framework and model provide a data-driven means to quantitatively evaluate alternative configurations of a regional RT system. Results suggest that the choice of location for future centers can significantly improve geographic access to RT.

Autophagy and cancer--issues we need to digest.

Autophagy is an evolutionarily conserved catabolic pathway that has multiple roles in carcinogenesis and cancer therapy. It can inhibit the initiation of tumorigenesis through limiting cytoplasmic damage, genomic instability and inflammation, and the loss of certain autophagy genes can lead to cancer. Conversely, autophagy can also assist cells in dealing with stressful metabolic environments, thereby promoting cancer cell survival. In fact, some cancers rely on autophagy to survive and progress. Furthermore, tumour cells can exploit autophagy to cope with the cytotoxicity of certain anticancer drugs. By contrast, it appears that certain therapeutics require autophagy for the effective killing of cancer cells. Despite these dichotomies, it is clear that autophagy has an important, if complex, role in cancer. This is further exemplified by the fact that autophagy is connected with major cancer networks, including those driven by p53, mammalian target of rapamycin (mTOR), RAS and glutamine metabolism. In this Commentary, we highlight recent advances in our understanding of the role that autophagy has in cancer and discuss current strategies for targeting autophagy for therapeutic gain.