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INTRODUCTION: People released from prison have an increased risk of morbidity, including from nonfatal violence. We examined the incidence and predictors of violence-related morbidity after release from prison and investigated whether there are differences according to sex and Indigenous status. METHODS: Baseline data were collected from 1325 people within 6 weeks of release from prisons in Queensland, Australia, between 1 August 2008 and 31 July 2010. Data were linked to state-wide health (ambulance, emergency department and hospital) and prison records, and national death records until 31 July 2012. Predictors were identified using a multivariable Andersen-Gill model. Differences according to sex and Indigenous status were investigated using effect modification. RESULTS: A total of 225 (18.2%) people experienced 410 violence-related events that were recorded in health records. The incidence was 12.8 per 100 person-years [95% confidence interval (CI) 11.7, 14.1]. Risk factors for violence-related morbidity included diagnosed mental illness [hazard ratio (HR) = 2.0, 95% CI 1.1, 3.8], substance use disorder (HR = 1.6, 95% CI 1.1, 2.3) or dual diagnosis (HR = 3.2, 95% CI 2.2, 4.8); high-risk alcohol use (HR = 2.1, 95% CI 1.5, 2.8); being Indigenous (HR = 1.7, 95% CI 1.2, 2.5); and two or more prison releases (HR = 1.7, 95% CI 1.2, 2.6). Indigenous status modified the risk of violence-related morbidity, with Indigenous men having twice the risk of non-Indigenous men (HR = 1.9, 95% CI 1.3, 2.8). DISCUSSION AND CONCLUSIONS: Approximately one in five people released from prisons in Queensland experienced violence-related morbidity. Coordinated and continuous mental health and substance use treatment from prison to the community may reduce the risk of violence-related morbidity in this population.

Thalattosuchians were a predominately marine clade of Mesozoic crocodylomorphs, including semi-aquatic teleosauroid and obligately pelagic metriorhynchid subclades. Recent advances in our understanding of thalattosuchian endocranial anatomy have revealed new details of the evolutionary transition from terrestrial to marine to pelagic taxa. Paranasal sinuses, however, have received little attention. Herein, we investigate the evolution of the paranasal sinus system and part of the upper respiratory system (nasopharyngeal ducts) in Thalattosuchia, by reconstructing the nasal and paranasal anatomy in CT scans of seven thalattosuchian skulls: one teleosauroid, two basal metriorhynchoids and four metriorhynchids. Our outgroups were: three extant crocodylian species (including adult and subadult skulls) and the basal crocodyliform Protosuchus. We found thalattosuchians exhibit exceptionally reduced paranasal sinus systems, solely comprising the antorbital sinus, as has been previously proposed. The semi-aquatic basal thalattosuchians Palgiopthalmosuchus gracilirostris and Pelagosaurus typus both have an antorbital sinus partially located medial to a reduced external antorbital fenestra and broadly communicating with the dorsal alveolar canal. In pelagic metriorhynchids, the antorbital cavity is more extensive than in basal taxa and possibly had an active function associated with a hypothesized accessory suborbital diverticulum, but our reconstructions are insufficient to confirm or reject the presence of such a diverticulum. The nasopharyngeal ducts of metriorhynchids are dorsoventrally enlarged, possibly enabling stronger ventilation. The sequence of acquisition of craniofacial adaptations show a mosaic pattern and appears to predate many skeletal adaptations, suggesting these changes occurred early in the thalattosuchian marine transition.

Why can some governments credibly commit to the rule of law and protection of property rights while others cannot? A potential answer involves deep historical traditions of institutions that constrain rulers. We explore whether experiences with representative assemblies in medieval/early modern Europe have left their mark on incomes and institutions today. We employ Stasavage’s (2010) data on representative assembly activity in 30 medieval/early modern European polities and the Putterman and Weil (2010) data on descendancy shares from circa 1500 populations to construct country-level measures of historical assembly experience. In a cross-country analysis, we find that assembly experience is positively and significantly correlated with current incomes, a measure of the rule of law and property rights, and the Polity IV index that emphasizes executive constraint. Once the latter two variables are controlled for, the estimated effect of assembly experience on current incomes is insignificant.

Aims: To estimate the treated prevalence of mental illness, substance use disorder (SUD) and dual diagnosis and the association between dual diagnosis and fatal and non-fatal overdose among residents of British Columbia (BC), Canada. Design: A retrospective cohort study using linked health, income assistance, corrections and death records. Setting: British Columbia (BC), Canada. Participants: A total of 921 346 BC residents (455 549 males and 465 797 females) aged 10 years and older. Measurements: Hospital and primary-care administrative data were used to identify a history of mental illness only, SUD only, dual diagnosis or no history of SUD or mental illness (2010–14) and overdoses resulting in medical care (2015–17). We calculated crude incidence rates of non-fatal and fatal overdose by dual diagnosis history. Andersen–Gill and competing risks regression were used to examine the association between dual diagnosis and non-fatal and fatal overdose, respectively, adjusting for age, sex, comorbidities, incarceration history, social assistance, history of prescription opioid and benzodiazepine dispensing and region of residence. Findings: Of the 921 346 people in the cohort, 176 780 (19.2%), 6147 (0.7%) and 15 269 (1.7%) had a history of mental illness only, SUD only and dual diagnosis, respectively; 4696 (0.5%) people experienced 688 fatal and 6938 non-fatal overdoses. In multivariable analyses, mental illness only, SUD only and dual diagnosis were associated with increased rate of non-fatal [hazard ratio (HR) = 1.8, 95% confidence interval (CI) = 1.6–2.1; HR = 9.0, 95% CI = 7.0–11.5, HR = 8.7, 95% CI = 6.9–10.9, respectively] and fatal overdose (HR = 1.6, 95% CI = 1.3–2.0, HR = 4.3, 95% CI = 2.8–6.5, HR = 4.1, 95% CI = 2.8–6.0, respectively) compared with no history. Conclusions: In a large sample of residents of British Columbia (Canada), approximately one in five people had sought care for a substance use disorder or mental illness in the past 5 years. The rate of overdose was elevated in people with a mental illness alone, higher again in people with a substance use disorder alone and highest in people with a dual diagnosis. The adjusted hazard rates were similar for people with substance use disorder only and people with a dual diagnosis.

A growing number of studies explore the determinants of economic freedom. Very few of them consider constitutional design. We study entrenchment, that is, the extent to which constitutions are more costly to change than ordinary policies and institutions. We utilize 1970–2017 data and study episodes where countries adopted meaningfully more entrenched constitutions. Using matching methods, we construct plausible counterfactuals against which to compare their post‐treatment changes in economic freedom. We report no significant effects on overall freedom. There is some evidence that entrenchment leads to smaller government size, more regulation, and weaker property rights. However, none of these results are robust.

We study the cost of breaching an implicit contract in a goods market, building on a recent study that documented the presence of such a contract in the Coca-Cola market, in the US, during 1886‒1959. The implicit contract promised a serving of Coca-Cola of a constant quality (the “real thing”), and of a constant quantity (6.5oz in a bottle or from the fountain), at a constant nominal price of 5¢. We offer two types of evidence. First, we document a case that occurred in 1930, where the Coca-Cola Company chose to incur a permanently higher marginal cost of production, instead of a one-time increase in the fixed cost, to prevent a quality adjustment of Coca-Cola, which would be considered a breach of the implicit contract. Second, we explore the consequences of the Company’s 1985 decision to replace the original Coke with the “New Coke.” Using the model of Exit, Voice, and Loyalty (Hirschman 1970), we argue that the unprecedented public outcry that followed the New Coke’s introduction, was a response to the Company’s breaching of the implicit contract. We document the direct and quantifiable costs of this implicit contract breach, and demonstrate that the indirect, although unquantifiable, costs in terms of lost customer goodwill were substantial.

We extend the theory of market-preserving federalism by ascertaining under what conditions it is likely to prevail. We argue that political-economic systems characterized by polycentric sovereignty — a self-enforcing structure of political property rights that links governance rights with governance revenues, and affords holders of political property rights a check on potentially predatory behavior — will promote market-preserving federalism. We show how the estates system of Medieval Europe was an example of polycentric sovereignty. We also show how the 17th Amendment to the U.S. Constitution represented a degradation of polycentric sovereignty. We conclude by discussing the relationship between governance systems characterized by polycentric sovereignty and social wealth creation, arguing that the structure of political property rights in a governance system is an important characteristic that has hitherto been neglected.

Aim The Cleveland Clinic has proposed a prognostic model of preoperative risk factors for failure of restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA). The model incorporates four predictive variables including completion proctectomy, handsewn anastomosis, diabetes mellitus and Crohn's disease. The aim of the present study was to perform an external validation of this model in a new cohort of patients having had RPC . Method Validation was performed in a multicentre cohort of 747 consecutive patients who had an RPC between 1990 and 2015 in three tertiary care facilities, using a Kaplan-Meier survival analysis and Cox regression analysis. The performance of the model was expressed using the Harrell's concordance error rate. The primary outcome measure was pouch survival with maintenance of anal function. Results During the study period, 45 (6.0%) patients experienced failure at a median interval of 31 months [IQR 9 - 82] from the original RPC. Multivariable analysis showed hand sewn anastomosis to be the only significant independent predictor. Harrell's concordance error rate was 0.42, indicating poor performance. Anastomotic leakage and Crohn's disease of the pouch were strong postoperative predictors for pouch failure and showed a significant difference in pouch survival after 10 years (p

The European Union (EU) may promote reforms to policies and institutions through at least two distinct mechanisms. First, accession to the EU requires countries to undertake reforms. Second, the EU common market may promote Tiebout jurisdictional competition. We empirically evaluate these two mechanisms using an unbalanced panel of up to 45 European countries during 1970–2010. We find that relationships between EU accession/membership and measures of policies/institutions are often statistically insignificant. Furthermore, when the estimated effects are statistically significant they are generally modest.

Background Intellectual disability and patient activation may be important drivers of inequities in health service access and health outcomes for people with intellectual disability transitioning from prison to the community. We assessed the association between intellectual disability and patient activation after prison release and examined whether this association varied, depending on whether intellectual disability was identified prior to prison release. Methods Overall, 936 prisoners were screened for intellectual disability by using the Hayes Ability Screening Index and completed the Patient Activation Measure (PAM) within 6 weeks of prison release and again at 1, 3 and 6 months post-release. We estimated the association between intellectual disability status and PAM scores by using a multilevel linear model, adjusting for sociodemographic, behavioural, health and criminogenic factors. We used propensity score matching to estimate the impact of being identified with intellectual disability prior to release from prison on the change in mean PAM score after prison release. Results Compared with those who screened negative for intellectual disability, ex-prisoners who screened positive, both with and without prior identification of intellectual disability, had significantly decreased mean PAM scores [(B = −4.3; 95% CI: −6.3, −2.4) and (B = −4.5; 95% CI: −6.8, −2.3), respectively] over 6 months of follow-up. Among those who reported being identified with intellectual disability prior to release from prison, a significant increase in PAM score at the 6-month follow-up interview (B = 5.89; 95% CI: 2.35, 9.42; P = 0.001) was attributable to being identified with intellectual disability prior to release. Conclusions Ex-prisoners screening positive for possible intellectual disability have decreased patient activation for at least 6 months after release from prison. However, individuals whose possible intellectual disability is unidentified appear to be particularly vulnerable. Incarceration is a pivotal opportunity for the identification of intellectual disability and for initiating transitional linkages to health and intellectual disability-specific community services for this marginalised population.

Modern crocodylians are a morphologically conservative group, but extinct relatives (crocodylomorphs) experimented with a wide range of diets, behaviors, and body sizes. Among the most unusual of these fossil groups is the thalattosuchians, an assemblage of marine-dwellers that transitioned from semiaquatic species (teleosaurids and kin) into purely open-ocean forms (metriorhynchids) during the Jurassic and Cretaceous Periods (ca 191-125 million years ago). Thalattosuchians can give insight into the origin of modern crocodylian morphologies and how anatomy and behavior change during a major evolutionary transition into a new habitat. Little is known, however, about their brains, sensory systems, cranial sinuses, and vasculature. We here describe the endocranial anatomy of a well-preserved specimen of the Jurassic semiaquatic teleosaurid Steneosaurus cf. gracilirostris using X-ray micro-CT. We find that this teleosaurid still had an ear well attuned to hear on land, but had developed large internal carotid and orbital arteries that likely supplied salt glands, previously thought to be present in only the fully pelagic metriorhynchids. There is no great gulf in endocranial anatomy between this teleosaurid and the metriorhynchids, and some of the features that later permitted metriorhynchids to invade the oceanic realm were apparently first developed in semiaquatic taxa. Compared to modern crocodylians, Steneosaurus cf. gracilirostris has a more limited set of pharyngotympanic sinuses, but it is unclear whether this relates to its aquatic habitat or represents the primitive condition of crocodylomorphs that was later elaborated. Anat Rec, 299:1511-1530, 2016. © 2016 Wiley Periodicals, Inc.

We consider a neoclassical growth model where labor collectively chooses labor share to maximize its steady-state wage rate. In the basic two-factor model, labor maximizes the steady-state wage rate by setting labor share equal to the elasticity of output with respect to labor. This is precisely the competitive outcome. Only when we consider the model with organized and unorganized labor types can organized labor raise its steady-state wage by choosing a higher than competitive labor share. Organized labor can benefit by choosing a higher labor share only at the expense of unorganized workers; not capital. We also analyze a version of the model that incorporates a tradeoff between collective bargaining opportunities and skill acquisition. All else equal, a higher skill premium leads organized labor to choose a higher labor share. Organized labor benefits again at the expense of skilled workers; not capital.

I. INTRODUCTION In September of 2008, the world seemed to fall apart. What seemed like economic slowdown in 2007 deteriorated into financial crisis, first in the United States and then in Europe and elsewhere. Since then, it has been hard to scan the headlines without reading about an economic crisis of some sort, somewhere. From 2008 to 2010, worldwide there were 21 sovereign debt crises, 28 currency crises, and a staggering 46 banking crises. (1) Governments often intervene into markets and implement policies intended to halt or mitigate crises. Recent interventions include the United Kingdom's 2008 bank rescue package, the 2009 American Recovery and Reinvestment Act (ARRA), and the European Union's 2008 stimulus plan. These interventions were all associated with increases in government expenditures and the scope of government decision making and control. Are they exceptional or the rule? If they are the rule, are the increases in government size and scope temporary expedients or are they permanent? We address these questions using data for up to 70 countries on economic crises from the 1960s through 2010. We estimate the relationship between crises and changes in the size and scope of government over both 5- and 10-year horizons. Unlike previous studies that consider banking crises, we also consider sovereign debt, currency, and inflation crises. Rahm Emanuel, then chief of staff to U.S. President-Elect Barack Obama, was quoted as saying: "You never want a serious crisis to go to waste." (2) His point (at least as widely interpreted) was that a crisis "creates a sense of urgency[;] actions that once appeared optional suddenly seem essential" (Seib 2008). In other words, a crisis facilitates political actions that, from the policymaker's perspective, would have been desirable regardless. Presumably, then, these political actions are not temporary expedients. Economists have also argued that temporary crises are likely to result in permanent expansions of government. Higgs (1987) argues that, during a crisis, individuals' confidence in the efficiency of markets is shaken. The demand for government intervention increases as a result. Increasing the scope for government, in particular, can require a relaxing of constitutional constraints that tend to persist beyond the crisis period. Furthermore, people become accustomed to the more extensive government. For these reasons, Higgs argues that while expansion of government may recede after the crisis, it is unlikely to return to precrisis levels. There is a ratchet effect and the expansion of government has a permanent component. Alternatively, Pitlik and Wirth (2003, 565) argue that it is "commonly shared wisdom among economists and political scientists [...] that crises promote the adoption of market-oriented reforms." (3) Pitlik and Wirth cite a number of examples in support of this view, including the reforms of Latin American countries at the beginning of the 1980s and the reforms of transition economies in the wake of the Soviet Union's demise. (4) According to this view, crises represent "moments of clarity" for politicians; realizations that bad policies need to be abandoned to avoid economic collapse (Harberger 1993; Williamson and Haggard 1994). Crises will result in a decrease in the size and scope of government. Relatedly, Alesina and Drazen (1991) and Drazen and Grilli (1993) argue that particular reforms impose costs on particular special interests, and that conflicts over the distribution of such costs delay reforms generally. Economies become "sclerotic," to use Olson's (1982) term. However, during a crisis, the more widely spread costs (i.e., those associated with the continuation of bad policies) increase. This increases the likelihood that reforms occur. Furthermore, there is a third possibility: crises lead to political polarization and, as a result, gridlock. This hampers both reforms and expansions of government. …

BackgroundReliable ascertainment of intellectual disability (ID) is important to identify those with special needs, in order for those needs to be met in the criminal justice system. Although the Hayes Ability Screening Index (HASI) is valid and widely used for the identification of possible ID, the risk of inter-rater bias between researchers when scoring the HASI has not yet been established. The current paper estimates the inter-rater reliability of the HASI in a sample of Indigenous and non-Indigenous prisoners in Western Australia.

The nuclear architecture of a cell may change as a result of various diseases, including cancer. A variety of nuclear features are, therefore, of interest to cell biologists. Recently, several studies have investigated the orientation of chromosomes in the interphase nucleus either visually or semi-automatically. In this article an automated method to measure this orientation is presented. The theoretical difference between performing these measurements in two and three dimensions is discussed and experimentally verified. The results computed from measurements of murine nuclei correspond with results from visual inspection. We found significant differences in the orientation of chromosome 11 between nuclei from a PreB cell line of BALB/c origin and primary B nuclei from congenic [T38HxBALB/c]N wild-type mice. Since our new automatic method concurs with both the visual and semi-automatic methods, we conclude that the automatic method can replace these methods in assessing chromosome orientation.

Introduction and Aims Attention deficit hyperactivity disorder (ADHD) is a known risk factor for substance use disorder (SUD); however, the potential additive contribution of comorbid ADHD to drug-specific dependence in SUD populations is largely unknown. The current study aimed to assess this association between ADHD symptoms and drug-specific SUD complexity and chronicity. Design and Methods A cross-sectional survey was administered to a convenience sample of 489 adults receiving SUD treatment at 16 Australian drug and alcohol treatment centres between September 2010 and August 2011. Participants were screened for adult ADHD symptoms using the Adult ADHD Self-Report Scale. Associations between ADHD screening status and drug-specific SUD complexity and chronicity were assessed using multivariate logistic and modified Poisson regression analysis, controlling for a range of potential confounders. Results Overall, 215 (44%) patients screened positive for concurrent adult ADHD and SUD. After Simes' correction, a significant positive association was observed between ADHD screening status and current amphetamine SUD (odds ratio (OR) = 1.85; 95% confidence interval (CI): 1.19–2.36). Patients who screened positive for ADHD were significantly more likely to report SUD history for heavy alcohol use (OR = 2.05; 95% CI: 1.21–3.45) and amphetamine (OR = 1.96; 95% CI: 1.26–3.06) as well as significantly increased risk of moderate (3–4 years) duration for benzodiazepine and amphetamine SUDs and long (≥5 years) duration for alcohol, opiates other than heroin or methadone, and amphetamine SUDs. Discussion and Conclusions The findings provide evidence that there is increased drug dependence complexity and chronicity in treatment-seeking SUD patients who screen positively for ADHD, specifically for amphetamine, alcohol, opiates other than heroin or methadone, and benzodiazepines. [Young JT, Carruthers S, Kaye S, Allsop S, Gilsenan J, Degenhardt L, van de Glind G, van den Brink W, Preen D. Comorbid attention deficit hyperactivity disorder and substance use disorder complexity and chronicity in treatment-seeking adults. Drug Alcohol Rev 2015;34:683–93]

Objectives To better understand the natural history and spectrum of fetal aortic stenosis (AS), we aimed to (1) determine the prenatal diagnosis rate of neonates with critical AS and a biventricular (BV) outcome, and (2) describe the findings at fetal echocardiography in patients diagnosed prenatally. Methods A multicenter, retrospective study was performed on neonates who presented with critical AS and who were discharged with a BV outcome from 2000 to 2013. The prenatal diagnosis rate was compared with that reported for hypoplastic left heart syndrome (HLHS). We reviewed fetal echocardiographic findings in patients who were diagnosed prenatally. Results In only 10 (8.5%) of 117 neonates with critical AS and a BV outcome was the diagnosis made prenatally, a rate significantly lower than that for HLHS in the contemporary era (82%; P

I. INTRODUCTION For more than 20 years economic freedom has been on the rise throughout the world. The Fraser Institute scores individual countries in terms of their economic freedom on a scale of 0-10, with 10 indicating most free. The average Economic Freedom of the World (EFW) score rose from about 5.7 in 1990 to about 6.9 in 2010. This increase of 1.2 points followed 20 years of stagnation where the average score declined slightly from about 5.88 in 1970. Starting in 1990, however, the average country saw its government expenditures share shrink, its regulations of markets become less burdensome, and its barriers to international trade become smaller. (1) The time period since 1990 has also corresponded to increasing global interconnectivity associated with the proliferation of the Internet. Following the introduction of commercial Internet service providers (ISPs) in 1989, the rate of worldwide Internet use has grown exponentially. Starting from less than .05% of the world population in 1990, nearly 30% of people used the Internet in 2010, and nearly 35% in 2012. (2) In this paper, we ask if these corresponding trends--increasing Internet use and increasing economic freedom--are not merely coincidental. To wit: is Internet use an important impetus for institutional change? Numerous researchers have stressed the importance of institutional quality for economic growth and well-being. (3) As Rodrik, Subramanian, and Trebbi (2004) famously proclaimed: institutions rule. The concept of economic freedom embodies various dimensions of institutional quality that have been shown to positively correlate with growth in cross-country samples (e.g., Ayal and Karras 1998; Dawson 1998; Gwartney, Lawson, and Holcombe 1999; Heckelman and Stroup 2000; Young and Sheehan 2014). (4) Economic freedom has, furthermore, been shown to correlate positively with health outcomes (Stroup 2007), political freedoms (Lawson and Clark 2010), the extent of trust within a population (Berggren and Jordahl 2006), and measures of subjective well-being (Gehring 2013; Nikolaev 2014; Ovaska and Takashima 2010). (5) Understanding which factors lead to the expansion of economic freedom is of clear importance to students of economic development. We estimate the relationship between Internet use and changes in EFW scores in a panel of up to 114 countries for the years 1990 through 2010. The estimated relationship is generally positive, but it also appears to be conditional on a country's initial level of economic freedom. Starting from an EFW score of about 6 or lower, the marginal effect is positive and statistically significant. Countries with 2010 EFW scores around this threshold included China, Nigeria, and Pakistan. Alternatively, our preferred estimates imply that starting from a score of about 7.7 or higher the relationship turns negative, and that the negative marginal effect is statistically significant starting from EFW scores greater than 8.5. However, only two countries, Hong Kong and Singapore, had 2010 EFW scores greater than 8.5. Our research is motivated by several studies that empirically identify cross-country institutional spillovers and their effects. Bosker and Garretsen (2009) find that an important determinant of a country's economic growth is the institutional quality of its neighbors. Leeson and Dean (2009), Seldadyo, Elhorst, and de Haan (2010), and de Groot (2011) all report evidence suggesting that countries cluster according to their institutional qualities. Furthermore, Simmons and Elkins (2004) find that countries do not indiscriminately copy their neighbor's policy innovations; rather, they specifically adopt liberalizing innovations. In all of the above studies, a country's neighbors are defined in the conventional, geographic sense of the term. Our point of departure is to acknowledge that the Internet allows individuals to transcend geography. In discussing the importance of institutional quality for economic development, Hayek (1960, 30) stresses that "we should provide the maximum of opportunity for unknown individuals to learn of facts that we ourselves are yet unaware of and to make use of this knowledge in their actions. …

We use the sensitivity of bank holding company equity returns to market interest rates as an indicator of perceived maturity mismatch. Based on data from 1990 to 2009, there is only weak evidence that market participants perceived banks to be effectively short-funded. However, looking at 1990�1996 and 1997�2009 subsamples separately, our results suggest that U.S. commercial banks were perceived as short-funded during the earlier time period but not the later. During this time of changing perceptions of maturity mismatch, banks were increasing their holdings of real estate loans as a share of total assets. We present evidence that, subsequent to 1996, market participants perceived real estate loans as having become effectively shorter-term.

The heterogeneous nature of urban environments means that atmospheric research ideally requires a dense network of sensors to adequately resolve the local climate. With recent advances in sensor technology, a number of urban meteorological networks now exist with a range of research or operational objectives. This article reviews and assesses the current status of urban meteorological networks, by examining the fundamental scientific and logistical issues related to these networks. The article concludes by making recommendations for future deployments based on the challenges encountered by existing networks, including the need for better reporting and documentation of network characteristics, standardized approaches and guidelines, along with the need to overcome financial barriers via collaborative relationships in order to establish the long-term urban networks essential for advancing urban climate research. Copyright © 2013 Royal Meteorological Society

The zinc-finger transcription factor, Mxr1 activates methanol utilization and peroxisome biogenesis genes in the methylotrophic yeast, Pichia pastoris. Expression of Mxr1-dependent genes is regulated in response to various carbon sources by an unknown mechanism. We show here that this mechanism involves the highly conserved 14-3-3 proteins. 14-3-3 proteins participate in many biological processes in different eukaryotes. We have characterized a putative 14-3-3 binding region at Mxr1 residues 212-225 and mapped the major activation domain of Mxr1 to residues 246-280, and showed that phenylalanine residues in this region are critical for its function. Furthermore, we report that a unique and previously uncharacterized 14-3-3 family protein in P. pastoris complements Saccharomyces cerevisiae 14-3-3 functions and interacts with Mxr1 through its 14-3-3 binding region via phosphorylation of Ser215 in a carbon source-dependent manner. Indeed, our in vivo results suggest a carbon source-dependent regulation of expression of Mxr1-activated genes by 14-3-3 in P. pastoris. Interestingly, we observed 14-3-3-independent binding of Mxr1 to the promoters, suggesting a post-DNA binding function of 14-3-3 in regulating transcription. We provide the first molecular explanation of carbon source-mediated regulation of Mxr1 activity, whose mechanism involves a post-DNA binding role of 14-3-3.

Transcriptional regulation of Snf1-dependent genes occurs in part by histone-acetylation-dependent binding of the transcription factor Adr1. Analysis of previously published microarray data indicated unscheduled transcription of a large number of Snf1- and Adr1-dependent genes when either the histone H3 or H4 tail was deleted. Quantitative real-time PCR confirmed that the tails were important to preserve stringent transcriptional repression of Snf1-dependent genes when glucose was present. The absence of the tails allowed Adr1 and RNA Polymerase II to bind promoters in normally inhibitory conditions. The promoters escaped glucose repression to a limited extent and the weak constitutive ADH2 transcription induced by deletion of the histone tails was transcription factor- and Snf1-independent. These effects were apparently due to a permissive chromatin structure that allowed transcription in the absence of repression mediated by the histone tails. Deleting REG1, and thus activating Snf1 in the H3 tail mutant enhanced transcription in repressing conditions, indicating that Snf1 and the H3 tail influence transcription independently. Deleting REG1 in the histone H4 tail mutant appeared to be lethal, even in the absence of Snf1, suggesting that Reg1 and the H4 tail have redundant functions that are important for cell viability.

Nanoparticles have significant potential as selective photo-absorbing agents for laser based cancer treatment. This study investigates the use of single walled carbon nanohorns (SWNHs) as thermal enhancers when excited by near infrared (NIR) light for tumor cell destruction. Absorption spectra of SWNHs in deionized water at concentrations of 0, 0.01, 0.025, 0.05, 0.085, and 0.1 mg/ml were measured using a spectrophotometer for the wavelength range of 200-1,400 nm. Mass attenuation coefficients were calculated using spectrophotometer transmittance data. Cell culture media containing 0, 0.01, 0.085, and 0.333 mg/ml SWNHs was laser irradiated at 1,064 nm wavelength with an irradiance of 40 W/cm{sup 2} for 0-5 minutes. Temperature elevations of these solutions during laser irradiation were measured with a thermocouple 8 mm away from the incident laser beam. Cell viability of murine kidney cancer cells (RENCA) was measured 24 hours following laser treatment with the previously mentioned laser parameters alone or with SWNHs. Cell viability as a function of radial position was determined qualitatively using trypan blue staining and bright field microscopy for samples exposed to heating durations of 2 and 6 minutes alone or with 0.085 mg/ml SWNHs. A Beckman Coulter Vi-Cell instrument quantified cell viability of samples treated with varyingmore » SWNH concentration (0, 0.01, 0.085, and 0.333 mg/ml) and heating durations of 0-6 minutes. Spectrophotometer measurements indicated inclusion of SWNHs increased light absorption and attenuation across all wavelengths. Utilizing SWNHs with laser irradiation increased temperature elevation compared to laser heating alone. Greater absorption and higher temperature elevations were observed with increasing SWNH concentration. No inherent toxicity was observed with SWNH inclusion. A more rapid and substantial viability decline was observed over time in samples exposed to SWNHs with laser treatment compared with samples experiencing laser heating or SWNH treatment alone. Samples heated for 6 minutes with 0.085 mg/ml SWNHs demonstrated increasing viability as the radial distance from the incident laser beam increased. The significant increases in absorption, temperature elevation, and cell death with inclusion of SWNHs in laser therapy demonstrate the potential of their use as agents for enhancing photothermal tumor destruction.« less

Urban land surface schemes have been developed to model the distinct features of the urban surface and the associated energy exchange processes. These models have been developed for a range of purposes and make different assumptions related to the inclusion and representation of the relevant processes. Here, the first results of Phase 2 from an international comparison project to evaluate 32 urban land surface schemes are presented. This is the first large-scale systematic evaluation of these models. In four stages, participants were given increasingly detailed information about an urban site for which urban fluxes were directly observed. At each stage, each group returned their models' calculated surface energy balance fluxes. Wide variations are evident in the performance of the models for individual fluxes. No individual model performs best for all fluxes. Providing additional information about the surface generally results in better performance. However, there is clear evidence that poor choice of parameter values can cause a large drop in performance for models that otherwise perform well. As many models do not perform well across all fluxes, there is need for caution in their application, and users should be aware of the implications for applications and decision making. Copyright  2010 Royal Meteorological Society

Single molecule studies make possible the characterization of molecu- lar processes and the identification of biophysical sub-populations that are not acces - sible through ensemble studies. We describe tethered particle motion, a method that allows one to study single molecules in their natural form without having to apply any external forces. The method combines darkfield microscopy with a metal nano- bead. It permits the study of the biophysical properties of the tethered particles, as well as protein-DNA interactions. The method is not suitable for in vivo studies, and we therefore describe two other methods that are appropriate for live-cell imaging.

This special issue is dedicated to Operations Management (OM) in Asia. A requirement for the special issue articles is that they have content related to the effects of national culture on OM. Here, the OM literature is combined with work from Anthropology and Women's Studies to provide a wide view of the effects of various Asian cultures on OM. The basic premise is that OM decisions may need to take culture into account: some OM practices are altered or precluded by culture, while others are more effective in some cultures than others. Numerous examples are provided involving quality management, shift scheduling, revenue management, facility location, layout, supply chain strategies, and other areas.

Glucose represses transcription of a network of co-regulated genes in Saccharomyces cerevisiae, ensuring that it is utilized before poorer carbon sources are metabolized. Adr1 is a glucose-regulated transcription factor whose promoter binding and activity require Snf1, the yeast homologue of the AMP-activated protein kinase in higher eukaryotes. In this study we found that a temperature-sensitive allele of MED14, a Mediator middle subunit that tethers the tail to the body, allowed a low level of Adr1-independent ADH2 expression that can be enhanced by Adr1 in a dose-dependent manner. A low level of TATA-independent ADH2 expression was observed in the med14-truncated strain and transcription of ADH2 and other Adr1-dependent genes occurred in the absence of Snf1 and chromatin remodeling coactivators. Loss of ADH2 promoter nucleosomes had occurred in the med14 strain in repressing conditions and did not require ADR1. A global analysis of transcription revealed that loss of Med14 function was associated with both up- and down- regulation of several groups of co-regulated genes, with ADR1-dependent genes being the most highly represented in the upregulated class. Expression of most genes was not significantly affected by the loss of Med14 function.

most probable break point ushering in an era of longer U.S. expansions, both absolutely and relative to subsequent recessions. Their analysis is based on cycle durations as defined by National Bureau of Economic Research (NBER) reference dates. However, much of macroeconomic analysis is based on (i) growth cycles (i.e., periods when the economy's production is above or below trend) rather than absolute increases or decreases in economic activity; and (ii) aggregate time series' volatility as the prime indicator of macroeconomic stability. In light of this, we reevaluate the March 1933 break point. First, using HP-filtered quarterly gross national product (GNP), our analysis of growth cycle durations still implies a break point near 1933. Second, we test for structural breaks in the volatility of GNP growth rates and deviations from trends. These tests suggest a structural break considerably later than

Background Prolongation of the QTc interval may be more common than previously believed among individuals with sickle cell disease (SCD). The clinical associations and natural history of QTc prolongation remain unclear in this population. Our objectives were to determine the prevalence of prolonged QTc and evaluate its relationship to clinical factors in children and young adults with SCD. Procedures We analyzed data from subjects 10 to 25 years old with SCD enrolled in our pulmonary hypertension screening protocol. Screening included echocardiography (ECHO), 12-lead electrocardiogram (ECG) and laboratory testing at steady state. QTc interval >440 msec was considered prolonged. Results ECG data from 76 subjects (57% male, mean age 14.2 ± 3 years old, range 10–24) were analyzed. We observed prolonged QTc in 29/76 (38%) subjects. Despite evidence of left ventricular hypertrophy (LVH) in 50/76 (66%) subjects, the frequency of LVH was not significantly different in subjects with and without QTc prolongation. When compared to subjects with normal QTc, subjects with prolonged QTc had higher mean tricuspid regurgitant jet velocity (2.51 ± 0.27 m/sec vs. 2.33 ± 0.26 m/sec, P = 0.010) as well as higher mean lactate dehydrogenase (433 ± 142 IU/L vs. 343 ± 142 IU/L, P = 0.000) and aspartate aminotransferase (48 ± 20 IU/L vs. 39 ± 15 IU/L, P = 0.026). A larger proportion of subjects with prolonged QTc also had a history of recurrent acute chest syndrome (66% vs. 38%, P = 0.038). Conclusions We conclude that QTc prolongation is a frequent finding in SCD not associated with LVH. Elevated pulmonary pressures, hemolysis and acute chest syndrome may represent risk factors for prolonged QTc in this population. Pediatr Blood Cancer 2009;52:842–846. © 2009 Wiley-Liss, Inc.

(See editorial comments by C. Seth Landefeld, pp 556–558)OBJECTIVES: To determine whether a practice-based in-tervention can improve care for falls, urinary incontinence,and cognitive impairment.DESIGN: Controlled trial.SETTING: Two community medical groups.PARTICIPANTS: Community-dwelling patients (357 atinterventionsitesand287atcontrolsites)aged75andolderidentified as having difficulty with falls, incontinence, orcognitive impairment.INTERVENTION: Intervention and control practices re-ceived condition case-finding, but only intervention practicesreceived a multicomponent practice-change intervention.MEASUREMENTS: Percentage of quality indicators sat-isfied measured using a 13-month medical record abstrac-tion.RESULTS: Before the intervention, the quality of care wasthe same in intervention and control groups. Screening tri-pled the number of patients identified as needing care forfalls, incontinence, or cognitive impairment. During the in-tervention, overall care for the three conditions was betterin the intervention than the control group (41%, 95% con-fidence interval (CI)535–46% vs 25%, 95% CI520–30%, Po.001). Intervention group patients received bettercare for falls (44% vs 23%, Po.001) and incontinence(37% vs 22%, Po.001) but not for cognitive impairment(44% vs 41%, P5.67) than control group patients. Theintervention was more effective for conditions identified byscreening than for conditions identified through usual care.CONCLUSION: A practice-based intervention integratedinto usual clinical care can improve primary care for fallsand urinary incontinence, although even with the interven-tion, less than half of the recommended care for these con-ditionswasprovided.More-intensiveinterventions,suchasembedding intervention components into an electronicmedical record, will be needed to adequately improve carefor falls and incontinence. J Am Geriatr Soc 57:547–555,2009.Key words: practice-based intervention; geriatric qualityof care; clinical care improvement

Concerns about the morbidity and mortality associated with tricuspid regurgitant jet velocity (TRJV) elevation, which may indicate pulmonary hypertension (PHT), in adults with sickle cell disease (SCD) have prompted growing interest in screening the pediatric sickle cell population. The goals of our study were to estimate the prevalence of TRJV elevation and determine its relationship to pulmonary function in children and young adults with SCD at baseline. Seventy-eight subjects (10–24 years old) with SCD underwent prospective screening by Doppler echocardiogram (ECHO), complete lung function evaluation, and laboratory testing as part of standard care at steady state. Tricuspid regurgitation was quantifiable in 68/78 (87%) subjects and peak TRJV was ≥2.5 m/sec in 26/78 (33.3%) evaluated. The frequency of obstruction, restriction, or abnormal gas exchange found on lung function evaluation was not significantly different in subjects with and without TRJV elevation. However, significant inverse correlations were observed between TRJV and both % predicted forced vital capacity (FVC) (r = −0.29, P = 0.022) and oxygen saturation (r = −0.26, P = 0.036). When compared to subjects without TRJV elevation, subjects with TRJV elevation had significantly lower % predicted forced expiratory volume in 1 sec (FEV1) (78.9 ± 14.4 vs. 86.6 ± 13.0%, P = 0.023), FVC (82.8 ± 14.1 vs. 90.7 ± 12.9%, P = 0.017), and oxygen saturation (95.8 ± 3.2 vs. 97.5 ± 2.4%, P = 0.016). We found that the combination of low hemoglobin and low % predicted FVC best predicted TRJV elevation (χ2 = 17.05, P = 0.001) in our cohort, correctly identifying 70% of cases and resulting in positive and negative predictive values of 60 and 74%, respectively. We conclude that in this young population with SCD, TRJV elevation that is not significantly associated with abnormal lung function is common at baseline. Pediatr Pulmonol. 2009; 44:281–289. © 2009 Wiley-Liss, Inc.

A survey of 15 firms showed that agreement among operations managers on competitive priorities is related to agreement on long-run strategic trade-off decisions and not to agreement on shortrun trade-offs. Furthermore, intended short-run actions were often in conflict with stated competitive priorities. Use of management-by-objectives linked to performance appraisal was related to agreement on competitive priorities.

To better understand the impact of changes in nuclear architecture on nuclear functions, it is essential to quantitatively elucidate the three-dimensional organization of nuclear components using image processing tools. We have developed a novel image segmentation method, which involves a contrast enhancement and a subsequent thresholding step. In addition, we have developed a new segmentation method of the nuclear volume using the fluorescent background signal of a probe. After segmentation of the nucleus, a first-order normalization is performed on the signal positions of the component of interest to correct for the shape of the nucleus. This method allowed us to compare various signal positions within a single nucleus, and also on pooled data obtained from multiple nuclei, which may vary in size and shape. The algorithms have been tested by analyzing the spatial localization of nuclear bodies in relation to the nuclear center. Next, we used this new tool to study the change in the spatial distribution of nuclear components in cells before and after caspase-8 activation, which leads to cell death. Compared to the morphological TopHat method, this method gives similar but significantly faster results. A clear shift in the radial distribution of centromeres has been found, while the radial distribution of telomeres was changed much less. In addition, we have used this new tool to follow changes in the spatial distribution of two nuclear components in the same nucleus during activation of apoptosis. We show that after caspase-8 activation, when centromeres shift to a peripheral localization, the spatial distribution of PML-NBs does not change while that of centromeres did. We propose that the use of this new image segmentation method will contribute to a better understanding of the 3D spatial organization of the cell nucleus.

SUMMARY: Renovascular hypertension may be caused by atherosclerotic disease or less commonly by fibromuscular dysplasia (FMD) of the renal arteries. Fibromuscular dysplasia is the commonest cause of renal artery stenosis in the younger age group and affects women predominantly. A review of our clinical database identified all patients with renovascular hypertension. All relevant clinical, biochemical and radiological findings on those with FMD were noted. the outcome of percutaneous transluminal renal angioplasty (PTRA) or reconstructive surgery was evaluated. Eight out of 62 (13%) patients with hypertension secondary to renovascular disease had FMD (all female; bilateral in four; mean age at diagnosis 37.6 years; age range 12–70 years). the mean duration of hypertension before the diagnosis of FMD was 3.3 years (range 3 months-10 years). A renal artery bruit was detected in five, hypertensive retinopathy in three and one had mild renal insufficiency. Twelve PTRAs were attempted on 10 stenotic lesions in six women. This cured the hypertension in three, while the other three have required less antihypertensive therapy. Percutaneous transluminal renal angioplasty was complicated by a trivial renal artery dissection in one, and a small upper pole infarction in another. One patient required a repeat PTRA. the other two women presented before the availability of PTRA and had successful reconstructive surgery. Fibromuscular dysplasia was the cause of hypertension in eight out of 62 (13%) patients with renovascular hypertension. Percutaneous transluminal renal angioplasty has shown encouraging results with a low complication rate. If technically feasible, PTRA should be attempted on all patients with FMD of the renal artery.

Of the 17 potential QIs, the expert panel process judged 16 to be valid, and one was rejected. The literature summaries that support each of the indicators judged to be valid in the expert panel process are described.

The P2X7 receptor has recently been described as a marker for lung alveolar epithelial type I cells. Here, we demonstrate both the expression of P2X7 protein and its partition into lipid rafts in the mouse lung alveolar epithelial cell line E10. A significant degree of colocalization was observed between P2X7 and the raft marker protein Caveolin-1; also, P2X7 protein was associated with caveolae. A marked reduction in P2X7 immunoreactivity was observed in lung sections prepared from Caveolin-1-knockout mice, indicating that Caveolin-1 expression was required for full expression of P2X7 protein. Indeed, suppression of Caveolin-1 protein expression in E10 cells using short hairpin RNAs resulted in a large reduction in P2X7 protein expression. Our data demonstrate a potential interaction between P2X7 protein and Caveolin-1 in lipid rafts, and provide a basis for further functional and biochemical studies to probe the physiologic significance of this interaction.

Human red cell anion exchanger AE1 (band 3) is an electroneutral Cl-HCO3- exchanger with 12-14 transmembrane spans (TMs). Previous work using Xenopus oocytes has shown that two co-expressed fragments of AE1 lacking TMs 6 and 7 are capable of forming a stilbene disulphonate-sensitive (36)Cl-influx pathway, reminiscent of intact AE1. In the present study, we create a single construct, AE1Delta(6: 7), representing the intact protein lacking TMs 6 and 7. We expressed this construct in Xenopus oocytes and evaluated it employing a combination of two-electrode voltage clamp and pH-sensitive microelectrodes. We found that, whereas AE1Delta(6: 7) has some electroneutral Cl-base exchange activity, the protein also forms a novel anion-conductive pathway that is blocked by DIDS. The mutation Lys(539)Ala at the covalent DIDS-reaction site of AE1 reduced the DIDS sensitivity, demonstrating that (1) the conductive pathway is intrinsic to AE1Delta(6: 7) and (2) the conductive pathway has some commonality with the electroneutral anion-exchange pathway. The conductance has an anion-permeability sequence: NO3- approximately I- > NO2- > Br- > Cl- > SO4(2-) approximately HCO3- approximately gluconate- approximately aspartate- approximately cyclamate-. It may also have a limited permeability to Na+ and the zwitterion taurine. Although this conductive pathway is not a usual feature of intact mammalian AE1, it shares many properties with the anion-conductive pathways intrinsic to two other Cl-HCO3- exchangers, trout AE1 and mammalian SLC26A7.

Previous studies on the effects of outsourcing have relied largely on anecdotal evidence, non-financial metrics or accounting-based measures that ignore intangible value. This study views outsourcing effects from its future revenue-generation potential, using market value. The relation between firms’ market valuation and outsourcing decisions is investigated using a cross-sectional valuation approach. Results based on Japanese manufacturing industries data from 1994 to 2002 indicate that core business-related outsourcing, offshore outsourcing, and shorter-term outsourcing have positive effects on outsourcing firms’ market value. In contrast, non-core business-related outsourcing, domestic outsourcing, and longer-term outsourcing are not found to enhance firm value.