Essays in Local Labor Economics: Dissertation Summary

This dissertation consists of three independent chapters all related to local labor market and urban economics. Chapter 1 studies the causes and welfare consequences of the increase in geographic sorting of workers by skill from 1980 to 2000. Chapter 2 examines the abilities of state and local governments to extract rent from private sector workers by charging high tax rates and spending the revenue on nonsocial desirable projects, such as excessive government worker wages. In Chapter 3, which is joint work with Guido Imbens, Michal Kolesar, and Thomas Barrios, we examine the standard practice in regression analysis of allowing for clustering in the error covariance matrix when the explanatory variable of interest varies at a more aggregate level (e.g., the state level) than the units of observation (e.g., individuals). This is a common econometric problem when using geographic variation to study local labor market outcomes

Essays in Local Labor Economics

This dissertation consists of three independent chapters. Chapter 1 examines the determinants and welfare implications of the increased geographic of workers by skill from 1980 to 2000. I estimate a structural spatial equilibrium model of local labor demand, housing supply, labor supply, and amenity levels. The estimates indicate that cross-city changes in firms' demands for high and low skill labor were the underlying forces driving the increase in geographic skill sorting. I find that the combined effects of changes in cities' wages, rents, and endogenous amenities increased well-being inequality between high school and college graduates by a significantly larger amount than would be suggested by the increase in the college wage gap alone.Economic

Vitamin D in Australia : issues and recommendations

BACKGROUND A significant number of Australians and people from specific groups within the community are suffering from vitamin D deficiency. It is no longer acceptable to assume that all people in Australia receive adequate vitamin D from casual exposure to sunlight.OBJECTIVE This article provides information on causes, consequences, treatment and prevention of vitamin D deficiency in Australia. DISCUSSION People at high risk of vitamin D deficiency include the elderly, those with skin conditions where avoidance of sunlight is required, dark skinned people (particularly women during pregnancy or if veiled) and patients with malabsorption, eg. coeliac disease. For most people, deficiency can be prevented by 5&ndash;15 minutes exposure of face and upper limbs to sunlight 4&ndash;6 times per week. If this is not possible then a vitamin D supplement of at least 400 IU* per day is recommended. In cases of established vitamin D deficiency, supplementation with 3000-5000 IU per day for at least 1 month is required to replete body stores. Increased availability of larger dose preparations of cholecalciferol would be a useful therapy in the case of severe deficiencies. * 40 IU (international units) = 1 &micro;g<br /

Non-structural protein-1 is required for West Nile virus replication complex formation and viral RNA synthesis

BACKGROUND: Flavivirus NS1 is a non-structural glycoprotein that is expressed on the cell surface and secreted into the extracellular space, where it acts as an antagonist of complement pathway activation. Despite its transit through the secretory pathway and intracellular localization in the lumen of the endoplasmic reticulum and Golgi vesicles, NS1 is as an essential gene for flavivirus replication. How NS1 modulates infection remains uncertain given that the viral RNA replication complex localizes to the cytosolic face of the endoplasmic reticulum. METHODS AND RESULTS: Using a trans-complementation assay, we show that viruses deleted for NS1 (∆-NS1) can be rescued by transgenic expression of NS1 from West Nile virus (WNV) or heterologous flaviviruses in the absence of adaptive mutations. In viral lifecycle experiments, we demonstrate that WNV NS1 was not required for virus attachment or input strand translation of the infectious viral RNA, but was necessary for negative and positive strand RNA synthesis and formation of the endoplasmic reticulum-associated replication complex. CONCLUSIONS: WNV RNA lacking intact NS1 genes was efficiently translated but failed to form canonical replication complexes at early times after infection, which resulted in an inability to replicate viral RNA. These results expand on prior studies with yellow fever and Kunjin viruses to show that flavivirus NS1 has an essential co-factor role in regulating replication complex formation and viral RNA synthesis

Transcriptomic profiling of 39 commonly-used neuroblastoma cell lines

Neuroblastoma cell lines are an important and cost-effective model used to study oncogenic drivers of the disease. While many of these cell lines have been previously characterized with SNP, methylation, and/or mRNA expression microarrays, there has not been an effort to comprehensively sequence these cell lines. Here, we present raw whole transcriptome data generated by RNA sequencing of 39 commonly-used neuroblastoma cell lines. These data can be used to perform differential expression analysis based on a genetic aberration or phenotype in neuroblastoma (e.g., MYCN amplification status, ALK mutation status, chromosome arm 1p, 11q and/or 17q status, sensitivity to pharmacologic perturbation). Additionally, we designed this experiment to enable structural variant and/or long-noncoding RNA analysis across these cell lines. Finally, as more DNase/ATAC and histone/transcription factor ChIP sequencing is performed in these cell lines, our RNA-Seq data will be an important complement to inform transcriptional targets as well as regulatory (enhancer or repressor) elements in neuroblastoma

Viruses, Vaccines and the Public

Current research in virology is changing public conceptions about vaccines and infectious disease. The University of Nebraska State Museum collaborated with research virologists, science writers, artists and learning researchers to create public outreach materials about viruses and infectious disease. The project, funded by the National Institute of Health’s SEPA program, developed comics, a book with Carl Zimmer, and other materials and programs. The project launched three kinds of learning research: 1) a survey of Nebraska adults on their opinions about vaccines and infectious disease; 2) a study comparing the mental models of viruses, vaccines and infection from virologists, teachers, and students; and 3) a controlled study 873 high school students randomly assigned to read either a comic or a text-based essay with the same virus information

Rapid and Highly Informative Diagnostic Assay for H5N1 Influenza Viruses

A highly discriminative and information-rich diagnostic assay for H5N1 avian influenza would meet immediate patient care needs and provide valuable information for public health interventions, e.g., tracking of new and more dangerous variants by geographic area as well as avian-to-human or human-to-human transmission. In the present study, we have designed a rapid assay based on multilocus nucleic acid sequencing that focuses on the biologically significant regions of the H5N1 hemagglutinin gene. This allows the prediction of viral strain, clade, receptor binding properties, low- or high-pathogenicity cleavage site and glycosylation status. H5 HA genes were selected from nine known high-pathogenicity avian influenza subtype H5N1 viruses, based on their diversity in biologically significant regions of hemagglutinin and/or their ability to cause infection in humans. We devised a consensus pre-programmed pyrosequencing strategy, which may be used as a faster, more accurate alternative to de novo sequencing. The available data suggest that the assay described here is a reliable, rapid, information-rich and cost-effective approach for definitive diagnosis of H5N1 avian influenza. Knowledge of the predicted functional sequences of the HA will enhance H5N1 avian influenza surveillance efforts

Platinum bis(phosphine) complexes of 1,8-naphthosultam

The work in this project was supported by the Engineering and Physical Sciences Research Council (EPSRC).A series of bis(phosphine) platinum complexes 1-4 and 6-8 that bear the 1,8-naphthosultam ligand (L) have been synthesised. The nitrogen atom in L was deprotonated with sodium tert-butoxide to form the sodium salt. Metathetical reaction of the sodium salt (1 eq.) with the appropriate cis-dichlorobis(phosphine) platinum (1 eq.) in THF resulted in the formation of platinum complexes [Pt(PR3)2(L)Cl] (R3 = Ph3; 1, Ph2Me; 2, PhMe2; 3, Me3; 4), whilst reaction with [Pt(COD)Cl2] afforded [Pt(COD)(L)Cl] (5). The corresponding reaction employing two equivalents of L, two equivalents of NaOtBu and one equivalent of [Pt(PR3)2Cl2]/[Pt(COD)Cl2] yielded complexes [Pt(PR3)2(L)2] (R3 = Ph2Me; 6, PhMe2; 7, Me3; 8) and [Pt(COD)(L)2] (9). L, 1, 5 and 9 have been fully characterised, principally by multinuclear magnetic resonance and IR spectroscopy and mass spectrometry, the remaining members of the series were analysed by 31P NMR only. Unsymmetrical complexes 1-4 provide examples of AX spin systems, with appropriate satellites attributed to 31P NMR-195Pt coupling. X-ray structures determined for 1,8-naphthosultam L, and complexes 1, 5 and 9 and where appropriate the platinum metal geometry, N-S distance and ligand distortions were compared.PostprintPeer reviewe

A targeted psychological treatment for sleep problems in young people at ultra-high risk of psychosis in England (SleepWell): a parallel group, single-blind, randomised controlled feasibility trial

Background Sleep disturbance is common and problematic for young people at ultra-high risk of psychosis. Sleep disruption is a contributory causal factor in the occurrence of mental health problems, including psychotic experiences, anxiety, and depression. The implication is that treating sleep problems might have additional benefits on mental health outcomes in individuals at high risk. The present study had two aims: first, to establish the feasibility and acceptability of a randomised controlled trial to treat sleep problems with the aim of reducing psychotic experiences in young people at ultra-high risk of psychosis; and second, to provide proof of concept of the clinical efficacy of the treatment. Methods We did a parallel group, single-blind, randomised controlled feasibility trial in two National Health Service trusts in England. Eligible participants were aged 14–25 years, a patient of mental health services, assessed as being at ultra-high risk of psychosis on the Comprehensive Assessment of At-Risk Mental States, and having current sleep problems (score of ≥15 on the self-report Insomnia Severity Index [ISI]). Participants were randomly assigned (1:1) to either a targeted psychological therapy for sleep problems (SleepWell) plus usual care or usual care alone via an automated online system, with non-deterministic minimisation that balanced participants for ISI score and referring service. The SleepWell therapy was delivered on an individual basis in approximately eight 1-h sessions over 12 weeks. Assessments were done at 0, 3, and 9 months, with trial assessors masked to treatment allocation. The key feasibility outcomes were the numbers of patients identified, recruited, and retained, treatment uptake, and data completion. Treatment acceptability was measured with the Abbreviated Acceptability Rating Profile (AARP). In preliminary clinical assessments, the primary clinical outcome was insomnia at 3 and 9 months assessed with the ISI, reported by randomised group (intention-to-treat analysis). Safety was assessed in all randomly assigned participants. The trial was prospectively registered on ISRCTN, 85601537, and is completed. Findings From Nov 18, 2020, to Jan 26, 2022, 67 young people were screened, of whom 40 (60%) at ultra-high risk of psychosis were recruited. Mean age was 16·9 years (SD 2·5; range 14–23), and most participants identified as female (n=19 [48%]) or male (n=19 [48%]) and as White (n=32 [80%]). 21 participants were randomly assigned to SleepWell therapy plus usual care and 19 to usual care alone. All participants provided data on at least one follow-up visit. 39 (98%) of 40 participants completed the primary outcome assessment at 3 and 9 months. 20 (95%) of 21 participants assigned to SleepWell therapy received the prespecified minimum treatment dose of at least four sessions. The median treatment acceptability score on the AARP was 48 (IQR 46 to 48; n=17; maximum possible score 48). At the post-intervention follow-up (3 months), compared with the usual care alone group, the SleepWell therapy group had a reduction in insomnia severity (ISI adjusted mean difference –8·12 [95% CI –11·60 to –4·63]; Cohen's d=–2·67 [95% CI –3·81 to –1·52]), which was sustained at 9 months (ISI adjusted mean difference –5·83 [–9·31 to –2·35]; Cohen's d=–1·91 [–3·06 to –0·77]). Among the 40 participants, eight adverse events were reported in six participants (two [11%] participants in the usual care group and four [19%] participants in the SleepWell therapy group). One serious adverse event involving hospital admission for a physical health problem was reported in the SleepWell therapy group, and one patient in the usual care alone group transitioned to psychosis. None of these events were classed as being related to trial treatment or procedures. Interpretation A randomised controlled trial of a targeted psychological sleep therapy for young people at ultra-high risk of psychosis is feasible. Patients can be retained in the trial and assessments done by masked assessors. Uptake of the sleep therapy was high, and we found preliminary evidence of sustained reductions in sleep problems. A definitive multicentre trial is now needed. Funding NIHR Research for Patient Benefit and NIHR Oxford Health Biomedical Research Centre