Efficient targeted mutagenesis in the monarch butterfly using zinc finger nucleases

The development of reverse-genetic tools in non-model insect species with distinct biology is critical to establish them as viable model systems. The eastern North American monarch butterfly (Danaus plexippus), whose genome is sequenced, has emerged as a model to study animal clocks, navigational mechanisms and the genetic basis of long-distance migration. Here, we developed a highly efficient gene-targeting approach in the monarch using zinc-finger nucleases (ZFNs), engineered nucleases that generate mutations at targeted genomic sequences. We focused our ZFN approach on targeting the type 2 vertebrate-like cryptochrome gene of the monarch (designated cry2), which encodes a putative transcriptional repressor of the monarch circadian clockwork. Co-injections of mRNAs encoding ZFNs targeting the second exon of monarch cry2 into one nucleus stage embryos led to high frequency non-homologous end-joining-mediated, mutagenic lesions in the germline (up to 50%). Heritable ZFN-induced lesions in two independent lines produced truncated, nonfunctional CRY2 proteins, resulting in the in vivo disruption of circadian behavior and the molecular clock mechanism. Our work genetically defines CRY2 as an essential transcriptional repressor of the monarch circadian clock and provides a proof of concept for the use of ZFNs for manipulating genes in the monarch butterfly genome. Importantly, this approach could be used in other lepidopterans and non-model insects, thus opening new avenues to decipher the molecular underpinnings of a variety of biological processes

Impacts of Openness

This is the recording from the Impacts of Openness lightning talk session that was held on Friday, October 25, 2013, from 10:00 a.m. - noon in Watson Library, room 455 during the KU Libraries' celebration of Open Access Week.This event brings together several speakers from a variety of fields, each of whom will give a 10-minute presentation about the impact of openness in their work. More information about this event is available at http://openaccess.ku.edu/impacts-openness-lightning-talks-october-25

Profiles and outcome of traditional healing practices for severe mental illnesses in two districts of Eastern Uganda

Background : The WHO estimates that more than 80% of African populations attend traditional healers for health reasons and that 40%–60% of these have some kind of mental illness. However, little is known about the profiles and outcome of this traditional approach to treatment. Objective : The purpose of this study was to describe the profiles and outcome of traditional healing practices for severe mental illnesses in Jinja and Iganga districts in the Busoga region of Eastern Uganda. Methods : Four studies were conducted. Study I used focus group discussions (FGDs) with case vignettes with local community members and traditional healers to explore the lay concepts of psychosis. Studies II and III concerned a cross-sectional survey of patients above 18 years at the traditional healer's shrines and study IV was made on a prospective cohort of patients diagnosed with psychosis in study III. Manual content analysis was used in study I; quantitative data in studies II, III, and IV were analyzed at univariate, bivariate, and multivariate levels to determine the association between psychological distress and socio-demographic factors; for study IV, factors associated with outcome were analyzed. One-way ANOVA for independent samples was the analysis used in Study IV. Results : The community gave indigenous names to psychoses (mania, schizophrenia, and psychotic depression) and had multiple explanatory models for them. Thus multiple solutions for these problems were sought. Of the 387 respondents, the prevalence of psychological distress was 65.1%, where 60.2% had diagnosable current mental illness, and 16.3% had had one disorder in their lifetime. Over 80% of patients with psychosis used both biomedical and traditional healing systems. Those who combined these two systems seemed to have a better outcome. All the symptom scales showed a percentage reduction of more than 20% at the 3- and 6-month follow-ups. Conclusion : Traditional healers shoulder a large burden of care of patients with mental health problems. This calls for all those who share the goal of improving the mental health of individuals to engage with traditional healers

Divorce and the Excess Burden of Lawyers

We present a model where divorcing spouses can choose to hire lawyers in their divorce process. Spouses encounter incentives as in the classical prisoners' dilemma: Despite the zero sum nature of the game and the lawyers' fees, each spouse has an incentive to hire a lawyer. We propose a simple institutional setting allowing for joint lawyers in order to overcome this socially inefficient situation. This model is estimated and tested with rich micro-data from court records. Employing a multiple treatment matching procedure we estimate the causal effect of lawyers on the division of matrimonial property, on the length of the divorce process and on the quality of the divorce settlemen

Prevalence and demographics of anxiety disorders: a snapshot from a community health centre in Pakistan

<p>Abstract</p> <p>Background</p> <p>The developing world is faced with a high burden of anxiety disorders. The exact prevalence of anxiety disorders in Pakistan is not known. There is a need to develop an evidence base to aid policy development on tackling anxiety and depressive disorders in the country. This is the first pilot study to address the prevalence of anxiety disorders and their association with sociodemographic factors in Pakistan.</p> <p>Methods</p> <p>A cross-sectional study was conducted among people visiting Aga Khan University Hospital (AKUH), a tertiary care facility in Karachi, Pakistan. The point prevalence of anxiety amongst the sample population, which comprised of patients and their attendants, excluding all health care personnel, was assessed using the validated Urdu version of the Hospital Anxiety and Depression Scale (HADS). The questionnaire was administered to 423 people. Descriptive statistics were performed for mean scores and proportions.</p> <p>Results</p> <p>The mean anxiety score of the population was 5.7 ± 3.86. About 28.3% had borderline or pathological anxiety. The factors found to be independently predicted with anxiety were, female sex (odds ratio (OR) = 2.14, 95% CI 1.36–3.36, p = 0.01); physical illness (OR = 1.67, 95% CI 1.06–2.64, p = 0.026); and psychiatric illness (OR = 1.176, 95% CI 1.0–3.1, p = 0.048). In the final multivariate model, female sex (adjusted odds ratio (AOR) = 2, 95% CI 1.28–3.22) and physical illness (AOR = 1.56, 95% CI 0.97–2.48) were found to be significant.</p> <p>Conclusion</p> <p>Further studies via nationally representative surveys need to be undertaken to fully grasp the scope of this emerging public health issue in Pakistan.</p

Credit Market Competition and the Nature of Firms

Empirical studies show that competition in the credit markets has important effects on the entry and growth of firms in nonfinancial industries. This paper explores the hypothesis that the availability of credit at the time of a firm's founding has a profound effect on that firm's nature. I conjecture that in times when financial capital is difficult to obtain, firms will need to be built as relatively solid organizations. However, in an environment of easily available financial capital, firms can be constituted with an intrinsically weaker structure. To test this conjecture, I use confidential data from the U.S. Census Bureau on the entire universe of business establishments in existence over a thirty-year period; I follow the life cycles of those same establishments through a period of regulatory reform during which U.S. states were allowed to remove barriers to entry in the banking industry, a development that resulted in significantly improved credit competition. The evidence confirms my conjecture. Firms constituted in post-reform years are intrinsically frailer than those founded in a more financially constrained environment, while firms of pre-reform vintage do not seem to adapt their nature to an easier credit environment. Credit market competition does lead to more entry and growth of firms, but also to complex dynamics experienced by the population of business organizations

The Returns to Criminal Capital

Human capital theory (Becker 1962; Mincer 1958; Schultz 1960; 1961) posits that individuals can increase their labor market returns through investments in education and training. This concept has been studied extensively across several disciplines. An analog concept of criminal capital, while the focus of speculation and limited empirical study, remains considerably less developed theoretically and methodologically. This paper offers a formal theoretical model of criminal capital indicators and tests for greater illegal wage returns using a sample of serious adolescent offenders, many of whom participate in illegal income-generating activities. Our results reveal that, consistent with human capital theory, there are important illegal wage premiums associated with investments in criminal capital, notably an increasing but declining marginal return to experience and a premium for specialization. Further, as in studies of legal labor markets, we find strong evidence that, if left unaccounted for, non-random sample selection causes severe bias in models of illegal wages. Theoretical and practical implications of these results, along with directions for future research, are discussed

Is the Concept of Quality of Life Relevant for Multiple Sclerosis Patients with Cognitive Impairment? Preliminary Results of a Cross-Sectional Study

Background: Cognitive impairment occurs in about 50 % of multiple sclerosis (MS) patients, and the use of self-reported outcomes for evaluating treatment and managing care among subjects with cognitive dysfunction has been questioned. The aim of this study was to provide new evidence about the suitability of self-reported outcomes for use in this specific population by exploring the internal structure, reliability and external validity of a specific quality of life (QoL) instrument, the Multiple Sclerosis International Quality of Life questionnaire (MusiQoL). Methods: Design: cross-sectional study. Inclusion criteria: MS patients of any disease subtype. Data collection: sociodemographic (age, gender, marital status, education level, and occupational activity) and clinical data (MS subtype, Expanded Disability Status Scale, disease duration); QoL (MusiQoL and SF36); and neuropsychological performance (Stroop color-word test). Statistical analysis: confirmatory factor analysis, item-dimension correlations, Cronbach’s alpha coefficients, Rasch statistics, relationships between MusiQoL dimensions and other parameters. Principal Findings: One hundred and twenty-four consecutive patients were enrolled. QoL scores did not differ between the 69 cognitively non-impaired patients and the 55 cognitively impaired patients, except for the symptoms dimension. The confirmatory factor analysis performed among the impaired subjects showed that the structure of the questionnaire matched with the initial structure of the MusiQoL. The unidimensionality of the MusiQoL dimensions was preserved, and th