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Obesity has previously been thought to protect bone since high body weight and body mass index are associated with high bone mass. However, some more recent studies suggest that increased adiposity negatively impacts bone mass. Here, we aimed to test whether acute loss of adipose tissue, via adipocyte apoptosis, alters bone mass in age-related obese mice. Adipocyte apoptosis was induced in obese male FAT-ATTAC mice through AP20187 dimerizer-mediated activation of caspase 8 selectively in adipocytes. In a short-term experiment, dimerizer was administered to 5.5 month-old mice that were terminated 2 weeks later. At termination, the total fat mass weighed 58% less in dimerizer-treated mice compared with vehicle-treated controls, but bone mass did not differ. To allow for the detection of long-term effects, we used 9-month-old mice that were terminated six weeks after dimerizer administration. In this experiment, the total fat mass weighed less (− 68%) in the dimerizer-treated mice than in the controls, yet neither bone mass nor biomechanical properties differed between groups. Our findings show that adipose tissue loss, despite the reduced mechanical loading, does not affect bone in age-related obese mice. Future studies are needed to test whether adipose tissue loss is beneficial during more severe obesity.

The production of natural gas in Tanzania has contributed to national socioeconomic development. It is responsible for about 57% of the total generated electricity in the country. Despite a growing body of literature in this sector, little intellectual attention has been given to how local community members participate in and profit from this sector through an articulated engagement mechanism, employment and other benefits. Using a mix of qualitative research methods, we studied two gas-producing locations of Msimbati and Songosongo in southeastern Tanzania. Findings suggest inadequate local community participation. Belated and fast local community engagement by the government and gas companies resulted in unmanageable expectations to local communities. Hopes for more local employment opportunities dwindled as gas projects entered the production phase that required skilled workers. Stakeholders were unprepared without a gas sector institutional framework. Local communities have failed to tap the potential to produce and supply foodstuffs to gas companies. This has further restrained their potentially meaningful participation in this sector. Benefits emanating from gas activities have appeared inequitably shared among stakeholders. We call for well thought local community engagement approaches, equitable benefit-sharing modalities and local community preparedness to promote meaningful local community participation in the natural gas sector.

Public managers make decisions that may directly or indirectly affect the loss of human life, but there are few empirical analyses of whether and how public managers make tradeoffs among lives and other goods. We survey local government managers in the United States about tradeoffs using a vignette experiment with hypothetical flood scenarios. We find that managers make tradeoffs regarding lives saved compared with other features of the scenario, including project cost and property damage. Public works managers show a greater aversion to fatalities, while city managers and planners appear less averse. Our study also finds evidence of an equity preference.

Hurricane Sandy greatly disrupted the New York City (NYC) region’s transportation systems, electric power systems, work locations, and schools in 2012. This study uses survey responses from NYC Metropolitan Area residents to develop an agent-based model that depicts commuter travel behavior and adaptation after the disruption. Six scenarios were tested to quantify which systems were more critical to recover for an earlier return to productivity - defined as the ability to work for one’s employer. The recommended system restoration order depends on the pattern of normal commuting behavior. In the NYC Metropolitan Area, a larger share of commuters use transit to commute than in any other US metropolitan area. This resulted in the model indicating the subway/rail system recovery as the most important factor for returning the most people to productivity. The second most important factor is widespread power restoration itself, which allows residents to telework while waiting for the transportation system to recover. The next most important factor is the reopening of schools and daycares (with associated infrastructure systems), freeing parents to commute. The remaining expedited system recovery scenarios tested using the agent-based model resulted in a faster return to productivity than the baseline, but to a lesser degree than the subway/rail, power, and childcare systems scenarios. Additional analysis of recovery shows that households with higher annual income benefit more from power recovery compared to those with lower incomes. Moreover, the effectiveness of recovery scenarios can differ based on residential location and the extent of disruption in that location.

We sought to identify therapeutic targets for breast cancer by investigating the metabolic symbiosis between breast cancer and adipose tissue. To this end, we compared orthotopic E0771 breast cancer tumors that were in direct contact with adipose tissue with ectopic E0771 tumors in mice. Orthotopic tumors grew faster and displayed increased de novo lipogenesis compared to ectopic tumors. Adipocytes release large amounts of lactate, and we found that both lactate pretreatment and adipose tissue co-culture augmented de novo lipogenesis in E0771 cells. Continuous treatment with the selective FASN inhibitor Fasnall dose-dependently decreased the E0771 viability in vitro. However, daily Fasnall injections were effective only in 50% of the tumors, while the other 50% displayed accelerated growth. These opposing effects of Fasnall in vivo was recapitulated in vitro, intermittent Fasnall treatment increased the E0771 viability at lower concentrations and suppressed the viability at higher concentrations. In conclusion, our data suggest that adipose tissue enhances tumor growth by stimulating lipogenesis. However, targeting lipogenesis alone can be deleterious. To circumvent the tumor’s ability to adapt to treatment, we therefore believe that it is necessary to apply an aggressive treatment, preferably targeting several metabolic pathways simultaneously, together with conventional therapy.

Mice with impaired acute inflammatory responses within adipose tissue display reduced diet-induced fat mass gain associated with glucose intolerance and systemic inflammation. Therefore, acute adipose tissue inflammation is needed for a healthy expansion of adipose tissue. Because inflammatory disorders are associated with bone loss, we hypothesized that impaired acute adipose tissue inflammation leading to increased systemic inflammation results in a lower bone mass. To test this hypothesis, we used mice overexpressing an adenoviral protein complex, the receptor internalization and degradation (RID) complex that inhibits proinflammatory signaling, under the control of the aP2 promotor (RID tg mice), resulting in suppressed inflammatory signaling in adipocytes. As expected, RID tg mice had lower high-fat diet-induced weight and fat mass gain and higher systemic inflammation than littermate wild-type control mice. Contrary to our hypothesis, RID tg mice had increased bone mass in long bones and vertebrae, affecting trabecular and cortical parameters, as well as improved humeral biomechanical properties. We did not find any differences in bone formation or resorption parameters as determined by histology or enzyme immunoassay. However, bone marrow adiposity, often negatively associated with bone mass, was decreased in male RID tg mice as determined by histological analysis of tibia. In conclusion, mice with reduced fat mass due to impaired adipose tissue inflammation have increased bone mass.

ObjectivesThe main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalized for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization.Trial designHospitalized COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority.ParticipantsIncluded participants, men or women above 50 years of age, must be hospitalized for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden.Intervention and comparatorPatients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19.Main outcomesThe primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion).RandomisationRandomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + “standard of care”: “standard of care”). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina)Blinding (masking)This is an open-label trial.Numbers to be randomised (sample size)The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total.Trial StatusThe current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021.Trial registrationEudract number 2020-002027-10ClinicalTrials.gov Identifier: NCT04475601, registered June 8, 2020

More than 10% of women worldwide are diagnosed with polycystic ovary syndrome (PCOS), causing reproductive and metabolic disease. Hyperandrogenism is the main characteristic and elevated levels of androgens during pregnancy affect placenta function and fetal programming, which leads to reproductive and metabolic dysfunction in the offspring. Adiponectin secreted from adipose tissue improves whole-body metabolism, but its role during pregnancy is under explored. Adiponectin affects placental nutrient transport during pregnancy allowing for speculation that adiponectin can exert endocrine effects on the developing fetus. This study aims to investigate if, in prenatally androgenized (PNA) mice, adiponectin can prevent metabolic and reproductive dysfunction in female offspring. Adiponectin transgenic (APNtg) and wildtype (wt) female mice were mated with wt males, and received dihydrotestosterone or vehicle injections between gestational days 16.5-18.5 to induce a PCOS-like phenotype. The anogenital distance, a marker of in utero androgen exposure, was measured at 22 days of age, estrus cyclicity was recorded at 6 weeks of age, and metabolic measures were performed at 4 months of age. APNtg dams gave birth to significantly smaller offspring, independent of genotype, than wt dams. PNA increased f-insulin in all groups but insulin sensitivity was higher in wt mice from APNtg dams compared to wt mice from wt dams. Insulin resistance correlated with subcutaneous and visceral fat mass. PNA increased visceral fat % and adipocyte size in wt offspring from wt dams while wt and APNtg offspring from APNtg dams were protected against this effect. Visceral adipose tissue gene expression was unaltered in PNA wt offspring, regardless of the dam’s genotype, while APNtg offspring, regardless of PNA, had increased expression of adipogenic genes. Anogenital distance was increased in all PNA wt offspring independent of the dam’s genotype. There was, however, no difference between APNtg-vehicle and APNtg-PNA mice, suggesting that adiponectin overexpression protects against this effect. PNA leads to disrupted estrous cycle and fewer ovulations, but this effect was less pronounced in PNA wt mice from APNtg dams. Our data suggests that elevated maternal adiponectin protects the offspring against PNA induced metabolic dysfunction, and to a lesser extent reproductive dysfunction.

We present evidence that emergency managers exhibit some of the same decision biases, sensitivity to framing, and heuristics found in studies of the general public, even when making decisions in their area of expertise. Our national survey of county-level emergency managers finds that managers appear more risk averse when the outcomes of actions are framed as gains than when equivalent outcomes are framed as losses, a finding that is consistent with prospect theory. We also find evidence that the perceived actions of emergency managers in neighboring jurisdictions affect the choices a manager makes. In addition, our managers show evidence of attribution bias, outcome bias, and difficulties processing numerical information, particularly probabilities compared to frequencies. Each of these departures from perfect rationality points to potential shortfalls in public managers’ decision making. We suggest opportunities to improve decision making through reframing problems, providing training in structured decision-making processes, and employing different choice architectures to nudge behavior in a beneficial direction.

Emergency managers who work on floods and other weather-related hazards constitute critical frontline responders to disasters. Yet, while these professionals operate in a realm rife with uncertainty related to forecasts and other unknowns, the influence of uncertainty on their decision-making is poorly understood. Consequently, a national-level survey of county emergency managers in the United States was administered to examine how they interpret forecast information, using hypothetical climate, flood, and weather scenarios to simulate their responses to uncertain information. The study revealed that even emergency managers with substantial experience take decision shortcuts and make biased choices, just as do members of the general population. Their choices vary depending on such features as the format in which probabilistic forecasts are presented and whether outcomes are represented as gains or losses. In sum, forecast producers who consider these decision processes when developing and communicating forecasts could help to improve flood preparation and potentially reduce disaster losses.

Delays in cleaning up contaminated “brownfield” sites have led many states to adopt voluntary cleanup programs (VCPs), but the incentives they create remain poorly understood. We present the first theoretical model of VCPs, motivating it from a review of their institutional background, and the limited empirical literature on their effects. We show that tort liability alone leads to excessive development and insufficient risk mitigation, motivating the creation of mandatory cleanup programs (MCPs). We then show that MCPs with budget constraints lead to insufficient development and excessive risk mitigation, motivating the creation of VCPs. We analyze both the effect of VCPs on the extensive margin (whether a site is developed or not) and the intensive margin (mitigation level). VCPs do not increase mitigation efforts at all sites, but do increase the number of contaminated sites that are remediated and redeveloped. If designed properly they can induce highly-contaminated sites that are unknown to regulatory authorities to come forward to join the VCP.

Peripancreatic adipose tissue (PAT) is an understudied visceral fat depot that surrounds pancreas and is in touch with spleen and liver. Recent previous studies suggest that obesity-associated PAT inflammation accelerates pancreatic neoplasia in KrasG12D mice and that PAT conditioned-medium from pre-diabetic rats (9 weeks on high-fat diet; HFD) stimulates insulin secretion, proliferation and apoptosis in INS-1 cells. In this study, we aimed to better characterize PAT functionality in the context of HFD-induced obesity. PAT is a very small depot (0,5 ±0,04 mg) with a relatively high number of small adipocytes in unchallenged mice on chow, and we found that PAT expansion is less pronounced at early stages of HFD-feeding compared to the expansion of inguinal (IWAT), gonadal (GWAT) and mesenteric adipose tissues (MWAT). After 8-weeks HFD feeding the expansion of PAT was however comparable to the other three fat depots, but still PAT was more protected against the deleterious effects of HFD on adipose tissue inflammation and insulin resistance as judged by gene expression analysis (adiponectin, insulin receptor and inflammation markers). Feeding after 16-weeks HFD reduced the glucose and lipid uptake in all fat depots however, it was less pronounced in PAT; both fatty acid and glucose oxidation rates were higher in PAT compared to IWAT, GWAT and MWAT. Moreover, we noted that PAT is the only fat depot where the tissue weight correlates positively with liver weight in HFD-induced obese mice, and surgical removal of PAT followed by 16-week-HFD-feeding was associated with increased hepatic triglyceride content and accumulation of more and larger lipid droplets. PAT did not regenerate during this 16-week HFD time course suggesting that its precursor cells reside within the depot. Taken all data together, we propose that PAT, although it is located in the visceral compartment, can be considered as a metabolically/immunologically healthy fat depot that protects against hepatic steatosis in advanced obesity. Disclosure B. Chanclón: None. P. Micallef: None. E. Banke Nordbeck: None. Y. Wu: None. B. Wilder: None. J. Kanerva: None. P. Rorsman: None. I. Wernstedt Asterholm: None.

Emergency management as an institution has grown in size and scope in recent decades, but has this emergent profession brought better public decisions about managing hazards and risks? The evidence is mixed because though emergency managers have acted wisely and heroically, they are subject to institutional constraints as well as the same decision biases and barriers that affect other experts and professionals. We propose that emergency management can be improved and hazard vulnerability lessened more readily through better decision processes than through the traditional approach of incremental improvements in the quality of information. The current fascination with “big data” focuses on more and better information, but emergency and hazards managers should ensure that they use the data they already have access to well.

Obesity represents one of the most important health problems. Proper adipose tissue expandability is crucial for avoiding metabolic disorders. Furthermore, not all fat depots are functionally equal. Our previous work indicates that the expansion of the mesenteric adipose tissue (MWAT) plays a role in the intestinal barrier. Whether pancreas-associated adipose tissue (PAT) has a specific function is currently unknown. We hypothesize that storage of excess nutrients in PAT and PAT-derived adipokines (such as adiponectin) protect the pancreas against metabolic dysfunction during weight gain/obesity. An initial morphological study showed that PAT has an increased number of small, but fewer large adipocytes relative the adjacent MWAT. We compared the response to a 16-week high-fat diet (HFD)/obesity between PAT, other fat depots and pancreas. We found higher mRNA expression of inflammation markers in MWAT, inguinal (IWAT) and gonadal fat (GWAT), but not in PAT in response to HFD/obesity. HFD also downregulated the expression of insulin receptor and adiponectin in all fat depots, but not in PAT. The pancreas showed an increase in inflammatory and insulin resistance markers only after long-term (16 weeks) HFD exposure, a time point when also PAT displayed a reduction in insulin receptor and adiponectin expression. Smaller adipocytes are typically more functional than large adipocytes. Thus, these data suggest that PAT have an increased capacity for energy storage. This in turn may protect the pancreas against ectopic lipid accumulation and lipotoxicity. Moreover, our data show that PAT is protected against the deleterious effects of HFD, maintaining normal mRNA levels of adiponectin, insulin receptor and markers of inflammation. In summary, we believe that PAT protects the pancreatic beta-cells from lipotoxicity through its increased capacity for energy storage, sustained insulin sensitivity and possibly also increased insulin exposure because of its anatomical location. Disclosure B. Chanclon Garcia: None. Y. Wu: None. E. Banke Nordbeck: None. S. Musovic: None. C.S. Olofsson: None. P. Rorsman: None. I. Wernstedt Asterholm: None.

Using survey data from nearly 400 commuters, this paper identifies factors associated with commuter changes after Hurricane Sandy. Adaptations included changing transportation modes, routes...

This article reports on a study that featured a multiwave survey of Metrorail users in the months after a 2009 crash when two trains of Washington, DC's Metrorail system collided, resulting in nine deaths and 50 serious injuries. The authors report how perceptions of the crash appear to have changed over time, in terms of the tradeoffs among safety, speed, frequency of service, cost, and reliability that the transit users stated they were willing to make in the postaccident period. The authors also investigated how the crash altered transit users’ concerns about safety as a function of time and distance from the accident site. The authors use conditional logit models to examine tradeoffs among stated preferences for system performance measures after the accident. Results showed that respondents appear averse to longer headways between trains, longer travel durations, higher travel costs, a higher number of late trains, and a higher number of fatalities. The models also show evidence of higher aversion to fatalities from transit system operation among females compared to males. In addition, respondents less experienced with Metrorail travel and those with lower household incomes show higher aversion to fatalities. Aversion to fatalities appears to have increased between the early months after the accident and the end of the survey period, a finding that is contrary to the results of earlier studies. The authors conclude with a discussion of the choices across system features (e.g., fatalities versus costs versus convenience) and of the need for attending to safety perceptions after any public transportation crash.

The Washington, DC Metrorail collision in 2009 presents a rare opportunity to study rapid transit passengers’ responses to a highly publicized rail incident entailing injuries and fatalities. To investigate behavioral responses to the accident, particularly mode shifts, we conducted a web-based survey of approximately 300 commuters traveling on Metrorail after the accident who had used Metrorail in the 6 months prior to the collision. The most common response to the accident was avoidance of the first and last train cars. Some respondents substituted some Metrorail trips with other modes or took fewer Metrorail trips. To investigate factors influencing these behavioral responses, we employ multinomial logit models to explore the statistical association between respondent and travel characteristics and the choice among the options of (1) making no changes, (2) avoiding certain seating locations, (3) changing modes of transportation, and (4) changing both seating locations and modes of transportation. Results suggest that travel inertia, specifically mode inertia, exists, in that respondents generally prefer not to make mode or travel choice changes. However, some mode characteristics, such as cost differences and frequent delays have a statistically significant association with mode switching. Gender and the presence of children in the household correlate with the option selected.

Climate projections in many U.S. metropolitan areas show increases in daily temperature, and potential shifts in rainfall patterns toward stronger, more intense storms. At the same time, metropolitan regions continuing to experience population growth face the prospect of areal expansion and higher land-use intensities. The possible coupling of such developmental changes and more frequent intense precipitation events poses a litany of well-known challenges to storm-water management. This paper reports survey research that examines the experiences and expectations of engineers, planners, and other agency staff in storm-water management in the Washington-Baltimore metropolitan region in the context of climate change. We find that staff from jurisdictions with a high degree of development and strong population growth, and those with more work experience, engagement with climate issues in their work, and greater belief that scientists understand climate change, exhibit a higher level of concern with th...

Nearly every state in the United States has developed a voluntary land cleanup program to support an alternative, more decentralized approach to the revitalization of contaminated and underperforming land. Yet, despite the ubiquity of such programs and the thousands of properties enrolled in them, we know relatively little about their formation and attractiveness. This paper reports results from interviews of officials in voluntary cleanup program in all fifty states, and from a survey of program participants in one state. It seeks to characterize attitudes about the desirability and performance of voluntary cleanup programs and to motivate further research into policies to improve their efficacy. Results suggest the primacy of economic redevelopment in motivating state officials to develop voluntary cleanup program, with improving environmental quality, promoting regulatory reform, easing political pressures, and improving the cleanup process also playing roles. Program participants in the state examined in detail indicated that gaining liability protection, decreasing cleanup costs, and facilitating property sales constitute the most important potential benefits of enrolling properties in voluntary cleanup programs.

This paper examines the application by emergency managers in rural areas of forecasts of El Nino and other seasonal climate events to (1) improve the understanding of how diffuse networks can help overcome the obstacles to the use of complex scientific information and (2) to widen the use of seasonal forecasts to improve flood management. The investigation draws on ethnographic techniques of observation and conversation with emergency management networks in the state of Oregon, interviews of nearly 50 emergency managers in the state, and two detailed case studies of Oregon counties that have used seasonal climate forecasts to improve flood management. Emergency managers are more likely to use climate information tied to a time-specific and place-specific forecast and to feasible actions, and when the emergency managers are part of robust professional networks that include scientific professionals as well as end-users of forecast information.

Screening for founder mutations in BRCA1 and BRCA2 has been discussed as a cost-effective testing strategy in certain populations. In this study, comprehensive BRCA1 and BRCA2 testing was performed in a routine diagnostic setting. The prevalence of the BRCA1 stop mutation c.4183C>T, p.(Gln1395Ter), was determined in unselected breast and ovarian cancer patients from different regions in the Tyrol. Cancer registry data were used to evaluate the impact of this mutation on regional cancer incidence. The mutation c.4183C>T was detected in 30.4% of hereditary BRCA1-associated breast and ovarian cancer patients in our cohort. It was also identified in 4.1% of unselected (26% of unselected triple negative) Tyrolean breast cancer patients and 6.8% of unselected ovarian cancer patients from the Lower Inn Valley (LIV) region. Cancer incidences showed a region-specific increase in age-stratified breast and ovarian cancer risk with standardized incidence ratios of 1.23 and 2.13, respectively. We, thus, report a Tyrolean BRCA1 founder mutation that correlates to a local increase in the breast and ovarian cancer risks. On the basis of its high prevalence, we suggest that targeted genetic analysis should be offered to all women with breast or ovarian cancer and ancestry from the LIV region.

Interleukin-6 (IL-6) is released from working skeletal muscle during exercise. We investigated the acute and the long-term beneficial effects of IL-6 on exercise-induced glucose uptake in skeletal muscle and insulin sensitivity. The acute effect on exercise-induced glucose uptake was measured in IL-6-deficient (IL-6(-/-)) mice and wild-type control animals using a tracer technique. There was no difference in serum disappearance of (3)[H]2-deoxyglucose after a single bout of exercise between IL-6(-/-) and wild-type mice (13565 ± 426 versus 14343 ± 1309 d.p.m. min ml(-1), P = 0.5). The glucose uptake rate in the extensor digitorum longus muscle was, however, lower in IL-6(-/-) compared with wild-type mice (398 ± 44 versus 657 ± 41 nmol g(-1) min(-1), P < 0.01). In a long-term study, we monitored insulin sensitivity, serum retinol-binding protein-4 (RBP-4) levels, running activity, food intake, body weight and body composition in IL-6(-/-) and wild-type mice on a high-fat diet (HFD), with or without access to running wheels. In sedentary IL-6(-/-) and wild-type mice, the HFD decreased insulin sensitivity (glucose area under the concentration-time curve increased about 20% during an insulin tolerance test, P < 0.05 for both genotypes versus baseline) and led to a 30% increase in serum RBP-4 levels (P < 0.01 for both genotypes versus baseline). Wild-type mice with access to running wheels were protected against these effects of the HFD and maintained their baseline insulin sensitivity and serum RBP-4 levels. In contrast, IL-6(-/-) mice did not benefit from running to the same extent as wild-type animals. The IL-6(-/-) mice with access to running wheels had a similar decrease in insulin sensitivity to their sedentary littermates (glucose area under the concentration-time curve during an insulin tolerance test in runners versus sedentary IL-6(-/-) HFD mice, 312 ± 14 versus 340 ± 22 mmol min l(-1), P = 0.4) and displayed a 14% increase in serum RBP-4 compared with baseline levels (P < 0.01). Our results indicate that endogenous IL-6 contributes to the exercise-induced increase in insulin sensitivity, but plays only a minor role for glucose uptake into skeletal muscle during exercise.

The objective of this study was to determine the prevalence of and risk factors for work-related musculoskeletal disorders (WRMDs) in female physiotherapists with more than 15 years of job experience. A self-administered postal questionnaire was sent to 203 female physiotherapists with more than 15 years of job experience. Unconditional logistic regression was used to study the association between job exposures and the risk for WRMDs. The questionnaire was returned by 131 physiotherapists (64.5%). Of 99 subjects who answered specific questions about WRMDs, 52 (53.5%) were affected by WRMDs in at least one body part. Regions most affected were the hand/wrist (n=31; 58.5%) and the lower back (n=30; 56.5%). For hand/wrist pain, associations were found with: orthopedic manual therapy techniques (adjusted odds ratio [OR]=3.90; 95% confidence interval [CI]=1.2-13.1); working in awkward or cramped positions (OR=4.96; 95% CI=1.3-18.7); and high psychological job demands (OR=4.34; 95% CI=1.2-15.0). For lower back pain, associations were found with: working in awkward or cramped positions (adjusted OR=6.37; 95% CI=1.6-24.7); and kneeling or squatting (adjusted OR=4.76; 95% CI=1.4-15.9). More than half of the respondents reported WRMDs. General physical and psychosocial work-related exposures, as well as specific therapy tasks, were strongly associated with WRMDs. Larger, longitudinal studies are needed to determine the direction of causality.

This article examines social, economic, and political factors influencing the distribution of resources to local governments under the EPA Brownfields Program, an innovative federal effort to encourage the remediation and redevelopment of contaminated properties. Signed into law in 2002, the Small Business Liability Relief and Brownfields Revitalization Act provided the program with a congressional mandate, new tools to promote reuse such as liability protections, and increased funding up to a level of $250 million per year. This article contributes to research on environmental regulatory reform with an analysis of successful and unsuccessful local government applicants for EPA Brownfields Program support between 2003 and 2007. Building on prior research, we develop a series of expectations and an empirical model, and estimate the influence of program priorities, government and civic capacity, interest group pressures, and institutional politics. Results point to significant relationships between program priorities and award patterns. Contrary both to EPA's explicit commitments to equity and to analysis of pre-2003 award patterns, however, we find negative correlations between the proportions of local populations that are nonwhite or low-income and the likelihood of receiving an award. In addition, better-resourced governments and several dimensions of political representation show strong associations with the likelihood of winning awards. We conclude by discussing implications.

Many successful residential and other redevelopments have appeared at individual brownfield sites, yet the larger transformation of mixed-use urban neighborhoods distressed with numerous smaller, l...

Both the disproportionate loss of adipose tissue in the case of lipodystrophies and the disproportionate gain of adipose tissue in obesity are frequently associated with an increase in insulin resistance and its complications. Leptin replacement is a very promising therapeutic approach for the management of the complications of lipodystrophy. In contrast, leptin treatment for the reversal of obesity-related metabolic disorders has not proven to be successful. There is a need to better understand both of these phenomena. Mouse models of lipodystrophy may provide us with new pharmaceutical targets for the treatment and prevention of metabolic disturbances related to dysfunctional adipose tissue both in the context of lipodystrophy and obesity.

Die nachhaltige Entwicklung von Gesellschaft und Umwelt kann als mehrkriterielles Optimierungsproblem aufgefasst werden. Dabei besitzen nicht alle Teilkriterien zu jeder Zeit die gleiche Wertung. Im Beitrag wird ein Ansatz vorgestellt, der die situationsabhängige Bestimmung der Wichtungsfaktoren der Teilkriterien ermöglicht. An zwei Praxisbeispielen zur nachhaltigen Nutzung der Ressource Wasser werden Lösungen für die Führung komplexer hydrologischer und wasserwirtschaftlicher Systeme präsentiert.

Federal, state and local initiatives have emerged in the United States over the last decade to address the increasing number of ‘brownfield’ properties that are perceived to be contaminated. These initiatives are based on the beliefs that the social and financial benefits provided by redevelopment exceed the costs imposed by the interventions and that the reuse of sites can further local sustainability objectives by reducing growth pressures in undeveloped areas. This paper provides an examination of the current state of the practice of brownfields within which these interventions should be based. We summarize brownfields problems and federal, state and local efforts to address these problems. We then present ten stylized propositions about brownfields and draw on a range of surveys of the public and private sectors and other sources to explore the reality behind these. Finally we use the propositions to tie brownfields regeneration to sustainable local development through an area wide approach t...

Purpose: To identify and characterize cells of donor origin in the ocular surface of female recipients who have undergone allogeneic haematopoietic stem cell transplantation (allo-SCT) from a male donor. Methods: Cytological impressions from the eyes of nine allografted patients (17 eyes) were analysed. Donor cells were identified using sex-chromosome-specific fluorescence in situ hybridization (FISH). Cells were characterized by immunohistochemistry (IHC) using the CK3 and CK19 epithelial markers, the panleucocytic marker CD45 and the myofibroblast marker α-SMA. Results: No epithelial cells of donor origin were observed in the corneal or conjunctival samples. Cells of donor origin were found in the corneal samples, although these were often too degraded to allow characterization by IHC. In the conjunctiva, a median of 86% of the total number of cells were of recipient origin, including a subgroup (2%) of giant cells exhibiting polyploidy (range 4–18 n), found in the limbal region. Donor cells were detected in the conjunctiva of all nine patients at a median ratio of 9%, of which two-thirds were CD45+/α-SMA+. Conclusions: We observed superficially located myofibroblasts of donor origin in all allografted patients, but not in samples from healthy controls. Whether myofibroblasts are implicated in ocular graft-versus-host disease requires further studies.

We employ a mail survey of private developers that uses conjoint choice experiments and Likert-scaled attitudinal questions to examine preferences for policy instruments and incentives intended to encourage brownfield cleanup and redevelopment. Our analysis suggests that developers judge public hearing requirements at brownfield redevelopments unattractive, but that they place a relatively high value on liability relief—from both cleanup costs and claims by third parties. Reimbursement of environmental assessment costs is not particularly attractive. We also find considerable heterogeneity among developers in the value they place on these incentives, depending on their experience with contaminated sites. © 2006 by the Association for Public Policy Analysis and Management

Public agencies in the US have committed resources to encourage private investment in reusing contaminated sites. With public funds in short supply, the effectiveness of their efforts matters both to the agencies and the development community. This paper draws on a mail survey of private developers that uses conjoint choice experiments to investigate the relative attractiveness of incentives to promote residential infill on contaminated property. Results suggest protection from third party liability offers the most value, with protection from cleanup liability and relief from public hearing requirements also important. The findings indicate several opportunities for planners to promote infill on contaminated sites in a socially and environmentally appropriate manner.

This paper provides a survey of existing research on agent-based approaches to transportation and traffic management. A framework for describing and assessing this work will be presented and systematically applied. We are mainly adopting a logistical perspective, thus focusing on freight transportation. However, when relevant, work of traffic and transport of people will be considered. A general conclusion from our study is that agent-based approaches seem very suitable for this domain, but that this still needs to be verified by more deployed system.

Purpose: The German penal code exempts induced abortion from punishment if the pregnant woman wishes the termination of her pregnancy, if physicians foresee a present or future danger to the health of the pregnant woman and if there is no other way to avoid this danger. At the University Hospital of Erlangen we aimed to find the best individual decision for each case of requested late termination. Material and Method: Within a period of 12 months we had to decide on 13 such cases. For optimal management medical consultants with special knowledge on the relevant fetal anomalies were consulted. Legal and ethical aspects of late induced abortion were discussed in detail with the concerned couple. This was followed by a group discussion with all involved professionals, ending with a majority vote for or against abortion. The result of the vote was not binding for the fetal medicine specialist but facilitated his decision making. Result: In 12 of 13 cases a severe fetal malformation was the patients' main reason to request termination. Three women were diagnosed with overt psychiatric disease, the remainder showed signs of marked psychological disturbance. All patients lived in stable partnerships. Conclusion: The German penal code allows induced abortion after the 12th week for medical reasons. At the University Hospital of Erlangen our decision-finding process for late terminations involves professionals with special knowledge of fetal and neonatal disease facilitating the best individual decision within the scope of the law.

The problem domain in this work is a three-dimensional simulation of an underwater vehicle (AUV) that must navigate through obstacles towards a stationary goal point. The AUV has a limited set of sensors, including sonar, and can set its speed and direction each decision cycle. We wish to learn a strategy that is expressed as a set of reactive rules, (i.e. stimulus-response rules) that map sensor readings to actions to be performed at each decision time step. Note that the system does not learn a specific path, but a set of rules that reactively decide a move at each time step allowing the vehicle to reach its goal and avoid the obstacles.

Der Beitrag behandelt den Einsatz Künstlicher Neuronaler Netze (KNN) zur Modellbildung für nichtlineare dynamische, stationäre und instationäre Systeme. Es wird gezeigt, dass Radiale Basisfunktionsnetze (RBF) in Zusammenhang mit dem neu entwickelten schnellen Mehrschritt-Algorithmus die besten Identifikationsergebnisse liefern. Die Struktur des Netzes wird während des Lernprozesses automatisch so lange erweitert, bis für alle Trainingsdaten eine definierte Fehlerschranke unterschritten wird. Am Beispiel einer nichtlinearen Differenzengleichung erster Ordnung mit einem zeitvarianten Faktor werden die Eigenschaften des neuen Identifikationsverfahrens demonstriert und mit anderen bekannten Verfahren verglichen.

This paper examines the use of El Nino-Southern Oscillation (ENSO) forecasts for flood planning in the Pacific Northwest. The investigation relies on (1) case studies of three counties vulnerable to flooding that have had access to long-term forecasts of ENSO conditions, and (2) examination of data collected from a survey of nearly 60 local emergency managers, planners and public works staff. Results suggest that climate forecasts can facilitate flood planning when used by public and private policy entrepreneurs to build political support for flood mitigation measures. Understanding the social processes and regulatory machinery involved in applying these forecasts is critical to their more effective use. This use could be promoted by an extension service to disseminate climate information and proactive efforts to identify and work with entrepreneurial hazard planners and managers.

Environmental insurance (EI) can facilitate the redevelopment of potentially contaminated sites in distressed urban areas by providing a means to manage the environmental and financial risks at these properties. We draw on a survey and interviews of private brownfield developers to provide information on current EI utilization, factors that affect this, and ways in which public officials can facilitate its use when appropriate. We find that EI appears particularly relevant at sites where high-risk financing capital is used, off-site contaminant migration is likely, institutional controls are prevalent, or when developers lack adequate risk spreading across their project portfolios. Local governments and nonprofit organizations can promote EI use at both private and public properties through information dissemination, direct use of insurance-based risk transfer tools, and financial subsidies to developers for EI use.

Recent technical and scientific advances have increased the potential use of long term, seasonal climate forecasts for improving water resource management. This paper examines the role that forecasts, in particular those based on the El Nino Southern Oscillation (ENSO) cycle, can play in flood planning in the Pacific Northwest. While strong evidence exists of an association between ENSO signals and flooding in the region, this association is open to more than one interpretation depending on: (a) the metric used to test the strength of the association; (b) the definition of critical flood events; (c) site specific features of watersheds; and (d) the decision environment of flood management institutions. A better understanding and appreciation of such ambiguities, both social and statistical, will help facilitate the use of climate forecast information for flood planning and response.

Environmental managers in Russia face severe problems, both from Soviet-era and continuing environmental degradation and due to the weakness of current institutions with responsibilities for environmental protection. This paper draws on surveys, a case study of water pollution and workshops on Russian environmental decision making to explore prospects for environmental improvements. Using concepts from the regulatory reform literature, it focuses on the use of market incentives, the construction of a civil society and community involvement, and emphasizes that Russian non-governmental organizations may have a particularly important role to play in improving environmental management. Solidifying their legal base, coalition-building skills and the capability to conduct independent, pragmatic policy analyses would enhance their contribution.

Water utilities that rely on surface water may be vulnerable to future droughts and floods, a vulnerability that may be magnified by climate perturbations as well as shorter-term and, in some cases, ongoing changes in the political and regulatory environment in which utilities operate. Unfortunately, day-to-day responsibilities currently occupy most utility operators, leaving little time to plan for inherently uncertain effects. The record of actual responses to past droughts and floods can be illuminating, however, particularly when placed in the context of plausible hydrologic disruption and pressures such as population growth, floodplain development and new regulatory demands. This paper draws on interviews with water utility operators in the northwestern USA to highlight opportunities and constraints that water utilities may face vis-a-vis such disruptions. Key considerations affecting vulnerabilities include water rights, institutional barriers to efficient utility operations, hazard management polic...

We argue for the appropriateness of using software agents for the monitoring and control of bioprocesses. Different approaches to the design of individual agents as well as complete multi-agent systems are discussed. This is followed by a brief discussion of a number of successful agent-based monitoring and control applications from different domains. We conclude by discussing the advantages and disadvantages of agent technology for monitoring and control of bioprocesses. © 2002 Society of Chemical Industry

Resistin was originally identified as an adipocyte-derived factor upregulated during obesity and as a contributor to obesity-associated insulin resistance. Clinically, resistin has also been implicated in cardiovascular disease in a number of different patient populations. Our aim was to simultaneously address these phenomena.We generated mice with modest adipocyte-specific resistin overexpression. These mice were crossed with mice deficient in the LDL receptor (Ldlr (-/-)) to probe the physiological role of resistin. Both metabolic and atherosclerotic assessments were performed.Resistin overexpression led to increased atherosclerotic progression in Ldlr (-/-) mice. This was in part related to elevated serum triacylglycerol levels and a reduced ability to clear triacylglycerol upon a challenge. Additional phenotypic changes, such as increased body weight and reduced glucose clearance, independent of the Ldlr (-/-) background, confirmed increased adiposity associated with a more pronounced insulin resistance. A hallmark of elevated resistin was the disproportionate increase in circulating leptin levels. These mice thus recapitulated both the proposed negative cardiovascular correlation and the insulin resistance. A unifying mechanism for this complex phenotype was a resistin-mediated central leptin resistance, which we demonstrate directly both in vivo and in organotypic brain slices. In line with reduced sympathetic nervous system outflow, we found decreased brown adipose tissue (BAT) activity. The resulting elevated triacylglycerol levels provide a likely explanation for accelerated atherosclerosis.Resistin overexpression leads to a complex metabolic phenotype driven by resistin-mediated central leptin resistance and reduced BAT activity. Hypothalamic leptin resistance thus provides a unifying mechanism for both resistin-mediated insulin resistance and enhanced atherosclerosis.

The federal Superfund program, which cleans up properties contaminated with hazardous substances, has received relatively little attention in the planning literature. Yet, with ongoing Congressional efforts to tie site cleanups to expected land uses, high interest in promoting redevelopment of contaminated properties, and broader legislative and regulatory reform efforts to boost decentralized decision making, planners and other local stakeholders are increasingly becoming important players in Superfund and other federal environmental programs. In this article, I examine the experiences of three Superfund sites in the context of a devolutionary sharing of federal responsibilities with local-level stakeholders. My objectives are to highlight the local dynamics of cleanup and redevelopment and to demonstrate the importance of enforcement, incentives, and information in shaping these dynamics in Superfund and other environmental programs that rely increasingly on community involvement and intergover...

This article presents an overview of the current situation of euthanasia in Europe. Emphasis is given to the positions discussed in the Netherlands and in Germany. The current situation, the development of the legal positions, and the resulting debate are established by analysing English and German anesthesiological and medical-ethical journals. It has to be noted that many physicians are not satisfied with the terminology of euthanasia. The traditional concepts of euthanasia do not cover the aspect of accompanying terminally ill persons until they have died. The differentiation of active, passive, and indirect euthanasia does not correspond to the practical handling of the problem. Many physicians are in need of an open discussion of euthanasia-related issues. The way euthanasia is practiced in the Netherlands has strongly influenced the further development of the debate in Europe. Even though the Dutch model is rejected by the jurisdications of virtually all other countries, and official statements of medical corporations stick to the disapproval of active euthanasia, studies examining the attitudes towards euthanasia and the treatment of it in daily routine show that active interventions to shorten life are performed to different degrees outside of the Netherlands as well.

Planners often face disparate objectives in regulating the mining of aggregate minerals (sand, gravel, and crushed stone). In this article, the author uses the Baltimore-Washington region to examine how local jurisdictions manage aggregate minerals and the factors that help explain planners’ attitudes toward mineral protection. The study rests on a review of the region’s planning documents, examinations of specific planning practices in two counties, interviews of local planners, and statistical analysis. The author found that the sophistication of planning techniques for aggregate minerals ranges widely and that concern with mineral protection increases when both development pressures and resource supplies are high.