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Key Points A negative feedback loop, integrin–PI3K–ARAP3–integrin, controls integrin inactivation. Integrin inactivation promotes neutrophil transendothelial migration and recruitment., Neutrophils are abundant circulating leukocytes that are rapidly recruited to sites of inflammation in an integrin-dependent fashion. Contrasting with the well-characterized regulation of integrin activation, mechanisms regulating integrin inactivation remain largely obscure. Using mouse neutrophils, we demonstrate in this study that the GTPase activating protein ARAP3 is a critical regulator of integrin inactivation; experiments with Chinese hamster ovary cells indicate that this is not restricted to neutrophils. Specifically, ARAP3 acts in a negative feedback loop downstream of PI3K to regulate integrin inactivation. Integrin ligand binding drives the activation of PI3K and of its effectors, including ARAP3, by outside-in signaling. ARAP3, in turn, promotes localized integrin inactivation by negative inside-out signaling. This negative feedback loop reduces integrin-mediated PI3K activity, with ARAP3 effectively switching off its own activator, while promoting turnover of substrate adhesions. In vitro, ARAP3-deficient neutrophils display defective PIP3 polarization, adhesion turnover, and transendothelial migration. In vivo, ARAP3-deficient neutrophils are characterized by a neutrophil-autonomous recruitment defect to sites of inflammation.

Neutrophils, the most abundant circulating leukocytes in humans have key roles in host defense and in the inflammatory response. Agonist-activated phosphoinositide 3-kinases (PI3Ks) are important regulators of many facets of neutrophil biology. PIP3 is subject to dephosphorylation by several 5’ phosphatases, including SHIP family phosphatases, which convert the PI3K product and lipid second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3) into PI(3,4)P2, a lipid second messenger in its own right. In addition to the leukocyte restricted SHIP1, neutrophils express the ubiquitous SHIP2. This study analyzed mice and isolated neutrophils carrying a catalytically inactive SHIP2, identifying an important regulatory function in neutrophil chemotaxis and directionalityin vitroand in neutrophil recruitment to sites of sterile inflammationin vivo, in the absence of major defects of any other neutrophil functions analyzed, including, phagocytosis and the formation of reactive oxygen species. Mechanistically, this is explained by a subtle effect on global 3-phosphorylated phosphoinositide species. This work identifies a non-redundant role for the hitherto overlooked SHIP2 in the regulation of neutrophils, and specifically, neutrophil chemotaxis/trafficking. It completes an emerging wider understanding of the complexity of PI3K signaling in the neutrophil, and the roles played by individual kinases and phosphatases within.

We study the effect of unemployment on birth outcomes by exploiting geographical variation in the unemployment rate across local areas in England, and comparing siblings born to the same mother via family fixed effects. Using rich individual data from hospital administrative records between 2003 and 2012, babies' health is found to be strongly pro-cyclical. A one-percentage point increase in the unemployment rate leads to an increase in low birth weight and preterm babies of respectively 1.3 and 1.4%, and a 0.1% decrease in foetal growth. We find heterogenous responses: unemployment has an effect on babies' health which varies from strongly adverse in the most deprived areas, to mildly favourable in the most prosperous areas. We provide evidence of three channels that can explain the overall negative effect of unemployment on new-born health: maternal stress; unhealthy behaviours - namely excessive alcohol consumption and smoking; and delays in the take-up of prenatal services. While the heterogenous effects of unemployment by area of deprivation seem to be explained by maternal behaviour. Most importantly, we also show for the first time that selection into fertility is the main driver for the previously observed, opposite counter-cyclical results, e.g., Dehejia and Lleras-Muney (2004). Our results are robust to internal migration, different geographical aggregation of the unemployment rate, the use of gender-specific unemployment rates, and potential endogeneity of the unemployment rate which we control for by using a shift-share instrumental variable approach.

Attempts to control hospital expenditure by managing down General Practitioner (GP) referrals are reoccurring features of UK health policy. However, despite the best efforts of GPs to benchmark referral criteria, patient health may be damaged and other costs created by constraining referrals to targets. This paper adopts an indirect method to indicate whether rationing practice referrals may damage population health by distorting the use of health resources away from patients' interests. We utilise a comprehensive database at practice level that allows us to explore the relationship between referrals and emergency admissions, using a panel fixed effects model of admissions that allows for the endogeneity of referrals. We find that practice referrals are positively and partially correlated with emergency admissions, which is consistent with time-varying practice-level sickness shocks driving the relationship between referrals and emergency care, rather than shocks to the practice willingness to refer, or to system reforms. In this environment, government policy to constrain referrals may make the elective care less responsive to practice-level variations in illness, and thereby lower health.

BackgroundRecent studies have found an association between access to primary care and accident and emergency attendances, with better access associated with fewer attendances. Analyses of an association with emergency admissions, however, have produced conflicting findings.AimThis study investigated whether emergency admission rates in an area are associated with 1) the number of GPs, and 2) mean size of GP practice.Design and settingAnalysis was conducted utilising Hospital Episode Statistics, the numbers of GPs and GP practices, Office for National Statistics population data, Quality and Outcomes Framework prevalence data, and Index of Multiple Deprivation data, from 2004/2005 to 2011/2012, for all practices in England.MethodRegression analysis of panel data with fixed effects to address 1) a potential two-way relationship between the numbers of GPs and emergency admissions, and 2) unobservable characteristics of GP practices.ResultsThere is not a statistically significant relationship between the number of GPs in a primary care trust area and the number of emergency admissions, when analysing all areas. In deprived areas, however, a higher number of GPs is associated with lower emergency admissions. There is also a lower emergency admission rate in areas in which practices are on average larger, holding GP supply constant.ConclusionAn increase in GPs was found to reduce emergency admissions in deprived areas, but not elsewhere. Areas in which GPs are concentrated into larger practices showed reduced levels of emergency admissions, all else being equal.

Inflammation is a complex biological response that serves to protect the body's tissues following harmful stimuli such as infection, irritation or injury and initiates tissue repair. At the start of an inflammatory response, pro-inflammatory mediators induce changes in the endothelial lining of the blood vessels and in leukocytes. This results in increased vascular permeability and increased expression of adhesion proteins, and promotes adhesion of leukocytes, especially neutrophils to the endothelium. Adhesion is a prerequisite for neutrophil extravasation and chemoattractant-stimulated recruitment to inflammatory sites, where neutrophils phagocytose and kill microbes, release inflammatory mediators and cross-talk with other immune cells to co-ordinate the immune response in preparation for tissue repair. Many signalling proteins are critically involved in the complex signalling processes that underpin the inflammatory response and cross-talk between endothelium and leukocytes. As key regulators of cell–cell and cell–substratum adhesion, small GTPases (guanosine triphosphatases) act as important controls of neutrophil-endothelial cell interactions as well as neutrophil recruitment to sites of inflammation. Here, we summarise key processes that are dependent upon small GTPases in leukocytes during these early inflammatory events. We place a particular focus on the regulation of integrin-dependent events and their control by Rho and Rap family GTPases as well as their regulators during neutrophil adhesion, chemotaxis and recruitment.

Neutrophils are short-lived, abundant peripheral blood leukocytes that provide a first line of defense against bacterial and fungal infections whilst also being a key part of the inflammatory response. Chemokines induce neutrophil recruitment to inflammatory sites, where neutrophils perform a number of diverse functions that are aimed at fighting infections. Neutrophil effector functions are tightly regulated processes that are governed by an array of intracellular signaling pathways and initiated by receptor-ligand binding events. Dysregulated, neutrophil activation can result in excessive inflammation and host damage, as is evident in a number of autoimmune diseases. Rho family small GTPases and agonist-activated phosphoinositide 3-kinases (PI3Ks) represent two classes of key regulators of the highly specialized neutrophil. Here we review cross-talk between these important signaling intermediates in the context of neutrophil functions. We include PI3K-dependent activation of Rho family small GTPases and of their guanine nucleotide exchange factors and GTPase activating proteins, as well as Rho GTPase-dependent regulation of PI3K.

BackgroundThe English NHS faces financial pressures that may render the growth rates of elective admissions seen between 2001/2 and 2011/12 unsustainable. A better understanding of admissions growth, and the influence of policy, are needed to minimise the impact on health gain for patients.ObjectivesThis project had several objectives: (1) to better understand the determinants of elective activity and policy to moderate growth at minimum health loss for patients; (2) to build a rich data set integrating health, practice and local area data to study general practitioner (GP) referrals and resulting admissions; (3) to predict patients whose treatment is unlikely to be cost-effective using patient-reported outcomes and to examine variation in provider performance; and (4) to study how policies that aim to reduce elective admissions may change demand for emergency care. The main drivers of elective admissions growth have increased either supply of or demand for care, and could include, for example, technical innovations or increased awareness of treatment benefits. Of the factors studied, neither system reform nor population ageing appears to be a key driver. The introduction of the prospective payment tariff ‘Payment by Results’ appears to have led to primary care trusts (PCTs) having increasingly similar lengths of stay. In deprived areas, increasing GP supply appears to moderate elective admissions. Reducing the incidence of single-handed practices tends to reduce referrals and admissions. Policies to reduce referrals are likely to reduce admissions but treatments may be particularly reduced in the lowest referring practices, in which resulting health loss may be greatest. In this model, per full-time equivalent, female and highly experienced GPs identify more patients admitted by specialists.ResultsIt appears from our studies that some patient characteristics are associated with not achieving sufficient patient gain to warrant cost-effective treatment. The introduction of independent sector treatment centres is estimated to have caused an increase in emergency activity rates at local PCTs. The explanations offered for increasing elective admissions indicate that they are manageable by health policy.ConclusionsFurther work is required to understand some of the results identified, such as whether or not high-volume Clinical Commissioning Groups are fulfilling unmet need; why some practices refer at low rates relative to admissions; why the period effect, which results from factors that equally affect all in the study at a point in time, dominates in the age–period–cohort analysis; and exactly how the emergency and elective sections of hospital treatment interact. This project relies on the analysis of secondary data. This type of research does not easily facilitate the important input of clinical experts or service users. It would be beneficial if other methods, including surveys and consultation with key stakeholders, could be incorporated into future research now that we have uncovered important questions.FundingThe National Institute for Health Research Health Services and Delivery Research programme.

Neuropathic pain is a common side-effect of chemotherapy. Although precise mechanisms are unclear, oxidative stress and mitochondrial damage are involved. We investigated whether the mitochondria targeted antioxidant, MitoVitE, provided better protection against paclitaxel-induced mitochondrial damage in rat dorsal root ganglion (DRG) cells, than a non-targeted form of vitamin E, Trolox. We also determined whether MitoVitE, compared with duloxetine, could limit paclitaxel-induced mechanical hypersensitivity in rats.Mitochondrial function was measured in DRG cells exposed to paclitaxel with and without MitoVitE or Trolox. The effect of MitoVitE or Trolox on paclitaxel-induced cell killing in cancer cell lines was also determined. Rats received a cumulative dose of 8 mg kgPaclitaxel caused loss of membrane potential in DRG cells. At 100 µM paclitaxel median [range] change was 61[44-78]%, P 0.0001, which was ameliorated by MitoVitE (86[62-104]%) but not Trolox (46[46-57]%). Similarly, loss of metabolic activity and glutathione induced by paclitaxel (both P 0.0001) were reduced by MitoVitE but not Trolox. Cytotoxicity of paclitaxel was not affected by co-exposure of ovarian cancer cells to either MitoVitE or Trolox, but was slightly reduced against breast cancer cells, in the presence of Trolox. Mean (SD) areas under the curve of withdrawal thresholds at 6 h after injection in rats given paclitaxel + control, or + MitoVitE (P 0.0001) or + duloxetine (P 0.0001) were 110 (5), 145 (10) and 156 (13) respectively.Paclitaxel affected mitochondrial function and glutathione in DRG cells, which was abrogated by MitoVitE but not Trolox, without decreasing cancer cell cytotoxicity. In rats, paclitaxel-induced mechanical hypersensitivity was ameliorated by MitoVitE treatment to an extent similar to duloxetine. These data confirm mitochondria as a mechanistic target for paclitaxel-induced damage and suggest mitochondria targeted antioxidants as future therapeutic strategies.

We analyze how two key factors contribute to the high cost of healthcare in the US relative to the UK: (i) the higher private cost of medical education, and (ii) the higher risk of malpractice litigation. To assess the role of these factors we formulate, calibrate and simulate an equilibrium model of physician wages and the supply of medical graduates, work hours and treatment decisions of practicing physicians, and malpractice risk and malpractice insurance pricing. Consistent with prior work, we find direct costs of malpractice fines and insurance explain little of the high cost of healthcare in the US. However, the high private cost of medical education interacts with high malpractice risk in an interesting way: It leads doctors to (i) demand high wages and (ii) use excessive diagnostics to mitigate risk (“defensive medicine”). The agency problem that arises because patients cannot judge the efficacy of tests allows them to be over-prescribed. Together, these factors increase costs far more than direct malpractice costs. Specifically, physician salaries plus diagnostic tests comprise 4.04% of GDP in the US, compared to only 2.3% in the UK. The mechanisms emphasized in our model can largely explain the difference. Our policy simulations imply that more generous medical education subsidies would lead to both improved patient welfare and reduced overall health care costs in the US system (a Pareto improvement). We also find policies to (i) reduce malpractice risk, or (ii) induce doctors to internalize a small part of diagnostic costs, would have similar efficacious effects.

The national picture of the comparative costs and diagnoses of hospitalised homeless patients are examined using the 'no fixed abode' flag in English hospital statistics. Comparable studies sample patients in single cities, eg New York and Toronto. The most common diagnosis is substance misuse; the share of homeless NHS patients with this diagnosis is rising, and now equals that found in North American cities. About half of the cost of homeless patients relates to diagnoses of mental illness, although these comprise a much smaller share of homeless patients than in North America. Hospital costs for homeless patients - both total and per admission - have fallen significantly in recent years, primarily because of fewer admissions and shorter lengths of stay for mentally ill patients. Aims to reduce NHS costs at the level of individual institutions have often shaped policy. Broader policy to prevent and reduce homelessness offers substantial long-term reductions in the cost of chronic care.

There is strong policy interest, in England as elsewhere, in slowing the growth in emergency hospital admissions, which for older people increased by 3.3% annually between 2001/2 and 2012/3. Resource constrains have increased the importance of understanding rising emergency admissions, which in policy discourse is often explained by population aging. This study examines how far the rise in emergency admissions of people over 65 was due to population ageing, how far to the changing likelihood of entering hospital at each age, and how far to other factors which might be more amenable to policy measures. It shows that: admission rates rose with age from age 40 upward but each successive birth cohort experienced lower emergency admission rates after standardising for age and other effects. This downward cohort effect largely offset the consequences of an older and larger population aged over 65. Other factors which could explain increasing admissions, such as new technologies or rising expectations, appear more important than the changing size and age structure of the population as drivers of rising emergency admissions in old age. These findings suggest that stemming the rate of increase in emergency admissions of older people may be feasible, if challenging, despite population ageing.

Homeless people have complex problems. GP enhanced care (Pathway) has shown benefits. We performed a randomised, -parallel arm trial at two large inner city hospitals. Inpatient homeless adults were randomly allocated to either standard care (all management by the hospital-based clinical team) or enhanced care with input from a homeless care team. The hospital data system provided healthcare usage information, and we used questionnaires to assess quality of life. 206 patients were allocated to enhanced care and 204 to usual care. Length of stay (up to 90 days after admission) did not differ between groups (standard care 14.0 days, enhanced care 13.3 days). Average reattendance at the emergency department within a year was 5.8 visits in the standard care group and 4.8 visits with enhanced care, but this decrease was not significant. -Quality of life scores after discharge (in 108 patients) improved with enhanced care (EQ-5D-5L score increased by 0.12 [95% CI 0.032 to 0.22] compared wtih 0.03 [-0.1 to 0.15; p=0.076] with standard care). The proportion of people sleeping on the streets after discharge was 14.6% in the standard care arm and 3.8% in the enhanced care arm (p=0.034). The quality-of-life cost per quality-adjusted life-year was £26,000. The Pathway approach doesn't alter length of stay but improves quality of life and reduces street -homelessness.

© The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. Background: Hospital standardized mortality rates (HSMRs) are considered to identify unsafe hospital care, but are criticized for disregarding unmeasured variations of both coding practice and outside of hospital palliative provision. Methods: The validity of HSMR methods is explored by examining whether the additional deaths implied by a Primary Care Trust (PCT) HSMR, as supplied by Dr Foster, are (i) detectable in English PCT mortality data and (ii) correlated with the percentage of PCT deaths out of hospital. Results: Higher PCT HSMRs were positively associated with higher area mortality, although this effect was significantly smaller than the HSMR model implies. There was a significant negative association between PCT HSMR and the percentage of deaths outside of hospital. Conclusions: This evidence suggests that the PCT HSMR is associated with all-cause area mortality, but it overstates the in-hospital mortality attributed to unsafe care. It also suggests that this overstatement is partially explained by the PCT HSMR reflecting the adverse case mix associated with a high share of deaths in hospital, i.e. the HSMR does not only reflect quality failings. Policy analyses that compare HSMRs to measure quality change may be biased by unbalanced samples of hospital patients.

ObjectiveVarious studies find that the share of emergencies in hospital admissions is higher in deprived areas, but both the explanation and policy implications are unclear. We estimate the extent to which this finding is due to a different disease mix in deprived areas, rather than other explanations such as patient behaviour and general practitioner effectiveness.DesignSecondary analysis using English Hospital Episode Statistics data, with disease for elective and emergency admissions in 2008/2009 coded at 186 blocks or 1230 categories and aggregated to lower layer super output area of residence. It is then linked to an appropriate measure of deprivation.Outcome measuresThe difference in the share of emergencies in hospital admissions between communities in the highest and lowest deciles of deprivation; and the percentage of this difference that is explained if areas in the least deprived decile have the same disease mix as those in the most deprived decile.ResultsUsing the finest disease classification scheme (1230 categories), 71% of the higher share of admissions that were emergencies in decile 1 areas relative to decile 10, is explained by the “adverse” case mix (CM) in deprived areas. The remainder reflects the higher relative use of emergency care in deprived areas for the same conditions. Higher incidence of respiratory and circulatory diseases in deprived areas explains about 30% of the CM contribution. Diseases of the digestive system and abdomen have a high relative use of emergency care in deprived areas.ConclusionsThe higher use of emergency care in deprived areas is primarily a symptom of the higher prevalence of diseases which have high national rates of emergency to elective care—especially respiratory diseases—rather than an indication of less effective primary care. Nevertheless, there is a higher share of emergency care in admissions in deprived areas for several diseases, most notably of the digestive system.

Do the young and educated in LDCs have a greater preference to locate in big cities? If so, this may help to explain how cities spatially concentrate the educated and young, and why the rising share of these workers in many LDCs may contribute to city growth. This paper explores migration flows into and out of Egypt's three largest cities. We study whether the higher shares of such workers in cities arise because these workers perceive relatively greater benefits from living in cities, given relative urban/rural wage rates, or because the relative demand for these workers rises with city size.

This paper explores entrepreneurship amongst return migrants, how their business locations and characteristics differ from other businesses, and the implications for rural–urban inequality. First, we examine, amongst returnees, the determinants of investment in a project/enterprise. Secondly, we study the impact of return migration on the characteristics and nature of non-farm small enterprises using a sample of return migrants and non-migrant owners of enterprises. Our data indicate that although the share of return migrants originating in urban areas is almost equal to those from rural areas, and that migrants tend to return to their origin region, urban areas benefit more than rural areas from international savings. The empirical evidence suggests that overseas savings, and the duration of stay overseas, have positive separate effects on the probability of investing in a project/enterprise amongst returnees. Furthermore, returnees of urban origin are more likely than rural ones to invest in a non-farm enterprise. The findings also indicate that there is a regional bias in the location of firms and jobs created by returnees compared with non-migrants, in favour of the capital city. Thus, overall, the results support a positive impact of return migration on enterprise investment in urban areas driven by the preference of returnees to invest in urban areas.

Workers will not pay for general on-the-job training if contracts are not enforceable. Firms may if there are mobility frictions. Private information about worker productivities, however, prevents workers who quit receiving their marginal products elsewhere. Their new employers then receive external benefits from their training. In this paper, training firms increase profits by offering apprenticeships which commit firms to high wages for those trainees retained on completion. At these high wages, only good workers are retained. This signals their productivity and reduces the external benefits if they subsequently quit. Regulation of apprenticeship length (a historically important feature) enhances efficiency. Appropriate subsidies enhance it further. This paper is now published at the reference given below, however the unpublished appendices are available to be downloaded.

Chemotherapy-induced neuropathic pain is a debilitating and common side effect of cancer treatment. Mitochondrial dysfunction associated with oxidative stress in peripheral nerves has been implicated in the underlying mechanism. We investigated the potential of melatonin, a potent antioxidant that preferentially acts within mitochondria, to reduce mitochondrial damage and neuropathic pain resulting from the chemotherapeutic drug paclitaxel. In vitro, paclitaxel caused a 50% reduction of mitochondrial membrane potential and metabolic rate, independent of concentration (20-100μM). Mitochondrial volume was increased dose-dependently by paclitaxel (200% increase at 100μM). These effects were prevented by co-treatment with 1μM melatonin. Paclitaxel cytotoxicity against cancer cells was not affected by co-exposure to 1μM melatonin of either the breast cancer cell line MCF-7, or the ovarian carcinoma cell line A2780. In a rat model of paclitaxel-induced painful peripheral neuropathy, pre-treatment with oral melatonin (5/10/50mg/kg), given as a daily bolus dose, was protective, dose-dependently limiting development of mechanical hypersensitivity (19/43/47% difference from paclitaxel control, respectively). Melatonin (10mg/kg/day) was similarly effective when administered continuously in drinking water (39% difference). Melatonin also reduced paclitaxel-induced elevated 8-isoprostane F2 α levels in peripheral nerves (by 22% in sciatic; 41% in saphenous) and limited paclitaxel-induced reduction of C fibre activity-dependent slowing (by 64%). Notably melatonin limited the development of mechanical hypersensitivity in both male and female animals (by 50/41%, respectively) and an additive effect was found when melatonin was given with the current treatment, duloxetine (75/62% difference, respectively). Melatonin is therefore a potential treatment to limit the development of painful neuropathy resulting from chemotherapy treatment. This article is protected by copyright. All rights reserved.

This paper contributes to a small but rapidly growing literature concerned with the potentially substantial implications of international migration for economic development in LDCs. We study the linkages between overseas employment, savings and entrepreneurial activity on return. In an econometric model of the probability of entrepreneurial activity, we find evidence supporting the hypotheses that both overseas savings, and the duration of stay overseas increase the probability of becoming an entrepreneur amongst literate returnees to Egypt. Amongst illiterate returnees, overseas savings alone increase the probability of becoming an entrepreneur. The results for literates suggest that skill acquisition overseas may matter more substantially than overcoming a savings constraint in explaining how overseas opportunities influence entrepreneurship on return. For illiterates, who usually accept menial positions overseas that offer little opportunity for learning, the opposite obtains.

Overseas employment has become more commonplace, and remittances have increased in similar proportions. For poor countries, remittances often substantially influence domestic expenditures and real exchange rates. We study overseas employment, remittances and domestic underemployment in a simple general equilibrium model with a non-traded good and minimum wage. The influence of population growth, rural productivity, and family altruism are examined. If remittances per migrant exceed domestic productivity then multiple equilibria may occur exhibiting high or low overseas employment. We discuss how the equilibrium with highest overseas employment conditionally Pareto dominates the other equilibria, and analyse policy co-ordination

This paper surveys analysis of the relationship between regional unemployment and labour mobility in the UK. A notable feature is the recent rise in the volatility of unemployment in the high wage region of the South East. This is explained by the relative growth of personal sector mortgage indebtedness in that region and greater consumption demand sensitivity to interest rate shocks. Regional unemployment rate differences are largely determined in the manual labour market and show only slight evidence of cyclically corrected convergence. This is underpinned by relatively low migration amongst manual workers, and little sensitivity of out-migration to regional labour market slack. Two regions have experienced persistent employment growth and attracted significant immigration of non-manual labour to low unemployment and increasing relative wage labour markets.

Jobs in the primary sector require firm-specific training, with wages determined as a result of bargaining. Firms pay for the training and since they are imperfectly informed about worker productivity, they test workers before hiring them. The secondary sector is competitive. Taking a job in the secondary sector signals low productivity, and therefore workers in the secondary sector are unable to get jobs in the primary sector. Open unemployment coexists with unfilled vacancies for low wage jobs.

In common with most OECD countries, unemployment in Britain has differed significantly between regions, but the persistence of relative regional unemployment rates in Britain has been, until recently, particularly striking. However, during the I990-93 recession, the relative regional unemployment pattern changed significantly for the first time in seventy years. Our primary purpose here is to understand these recent changes and to examine what might be learned about the contribution of economic policies to the amelioration of both regional unemployment rate differentials and the amplitude of regional unemployment cycles. Finally we ask whether there are any policy lessons to be drawn from the recent cycles in regional unemployment patterns which might provide insight into the amplitude of macro-economic cycles.

A two-region economy is studied in which one region has a competitive labor market whereas the other has a congested labor market in which locating a job uses resources. Workers loosing jobs in the congested region choose between migration followed by an immediate job offer and searching in the congested region. Steady-state decline of the labor force in the congested region is characterized together with equilibrium unemployment rates. Higher unemployment benefits may increase the rate of contraction of the congested market if the consequence for job matching outweighs that for migration conditional upon a given level of unemployment. Copyright 1992 by Royal Economic Society.

This retrospective study was undertaken to estimate the causes of severe sensorineural deafness (greater than 40 dB HL) in children. The children were identified from case notes of all referrals made to the Children's Hearing Assessment Centre during a 5-year period (from 1st January 1981 to 31st December 1985). Results were tabulated and conclusions drawn following a literature search. It was deduced that following better antenatal screening, a more active immunisation program and improvements in resuscitation of small preterm infants, there was a shift of cases from prenatal to perinatal causes. The proportion of cases of severe sensorineural deafness was much the same as in previous studies.

Whereas the long term goal of the work described focuses on issues related to estuaries in general, specific attention in this paper focuses on one – Weeks Bay, Alabama. This estuary is one of seventeen estuarine research reserves established as “natural field laboratories” for long-term scientific and educational programs (See Figure 1). Initially, Weeks Bay will be assumed to be a well mixed estuary such that two-dimensional (depth averaged) modeling can be used. The Waterways Experiment Station Implicit Flooding Model (WIFM), developed by the U.S. Army Corps of Engineers, Vicksburg, Mississippi is used. Complete data sets at equatorial tidal conditions were chosen from the field data available. Good agreement of model results with field measured water elevations was noted. These results are typical of the kind of agreement that is expected from two-dimensional depth averaged model simulations. As anticipated, there seems to be little or no movement of salt along the western shoreline when the Bon Secour Bay salinities are low. This indicates selective flow of Fish River water down the western side of the bay with a corresponding preference for Bon Secour Bay water to flow along the eastern shore.

This paper contributes to a small but rapidly growing literature concerned with the potentially substantial implications of international migration for economic development in LDCs. We study the linkages between overseas employment, savings and entrepreneurial activity on return. In an econometric model of the probability of entrepreneurial activity, we find evidence supporting the hypotheses that both overseas savings, and the duration of stay overseas increase the probability of becoming an entrepreneur amongst literate returnees to Egypt. Amongst illiterate returnees, overseas savings alone increase the probability of becoming an entrepreneur. The results for literates suggest that skill acquisition overseas may matter more substantially than overcoming a savings constraint in explaining how overseas opportunities influence entrepreneurship on return. For illiterates, who usually accept menial positions overseas that offer little opportunity for learning, the opposite obtains.

The Nottingham Paediatric Cochlear Implant Programme (NPCIP) specializes in the cochlear implantation of children under the age of 5 years. The initial stage in the pre-implant evaluation process is audiological assessment. In complex paediatric cases, behavioural audiological assessment may be difficult. In such cases, an objective measure to verify the aided hearing threshold is desirable. This study compares unaided and aided hearing thresholds, by both objective and behavioural techniques, in 20 children (aged

We build and test a model of how the growth of public jobs with wage premiums may help to explain the high and potentially inefficient level of urbanization in LDCs. Public jobs comprise about 40% of non- agricultural employment in LDCs, and have frequently offered substantial wage premiums. The Harris-Todaro model - and its extensions- suggest that wage premiums induce inefficient agglomeration, but that model critically assumes that wage premium jobs are allocated to favor local residents. This is inapplicable to public appointments in various LDCs. In the two-region general equilibrium model discussed here, the existence of spatial mobility costs are shown to be sufficient for wage premiums to result in inefficient agglomeration in regions that are allocated wage premium jobs. This weakens the assumptions under which wage premiums promote agglomeration, and extends the idea to LDCs such as Egypt, Ethiopia, and Kenya, where public jobs have, until recent reforms, offered substantial wage premiums, but are not allocated so as to favor local residents. The policy implications of this model also differ from Harris-Todaro. For example, if wage premiums are later reduced, the agglomeration persists: with mobility costs, the history of the location of jobs with wage premiums matters. We explore our hypotheses using Egyptian data. Between 1960 and 1986 the share of public jobs increased from 10% to 34% of the labor force, public jobs were centrally allocated, and offered a high total compensation premium. We find that public jobs’ growth has substantially altered the pattern of regional mobility and population shares, in a way that is consistent with this theory of agglomeration due to wage premiums and mobility friction Keywords; public sector, agglomeration, migration, developing country JEL classification: J61, J68, J60, J45, H11 & H40

This book provides a handy reference guide for medical practitioners who do not have specialist knowledge in paediatric audiology but who, nevertheless, will encounter many cases with mild hearing impairment in childhood, and occasional cases with more severe hearing problems. The test procedures used to assess the presence, type, nature and degree of hearing impairment are described with guidance on how to interpret the information provided in audiological reports. A book of this nature is long overdue and its presence is very timely given the appearance of various publications outlining requirements for improved quality and more effective service provision for hearing impaired children. The early detection of hearing problems is of fundamental importance in childhood and the medical practitioner has a central and active role in this process. Guidance on what practitioners can and should do is given in the text together with the answers to many questions which parents bring to the surgery.

It has become commonplace to attribute the recent increase in European redundancies and long-term unemployment to the ‘rigidity’ of its labour markets in comparison with those in Japan and United States. Yet this popular assertion has been supported by relatively little study of the forces which are ordinarily held to be responsible for these conjectured rigidities.

This paper integrates empirical analysis of the decision to migrate from a region with that of destination choice. Thus, the authors are able to study how net migration, and not just gross outflows, are influenced by regional labor-market circumstances. The results suggest that relative regional wages rates, but not relative unemployment and vacancy rates, are effective in reallocating labor from regions experiencing adverse demand shocks. The authors find little evidence that manual labor is migrating from those regions with relatively high manual unemployment but that migration plays a more conventional role in the regional adjustment process for nonmanual workers. Copyright 1994 by The London School of Economics and Political Science.

This paper describes and estimates a human capital model of whether unemployed workers seek retraining, and the timing of an application in an unemployment spell. The authors find that the probability of seeking retraining declines with age after twenty-seven years; with being attached to noncontracting industries; with greater contentment in unemployment compared with last job; and with union membership. Applications are increased by formal qualifications (CSE/O/A level) and decreased by vocational training, relative to no qualifications. Almost half the unemployed had sought retraining, and this was largely complete after nine months--below the mean interrupted unemployment duration. Copyright 1991 by Royal Economic Society.

This paper discusses why redundant skilled workers may be reluctant to accept interim unskilled jobs. If skilled work is more satisfying or less arduous for highly productive workers, then such workers invest more in moving quickly between skilled jobs. Thus, high productivity workers tend to search on-the-job, and if unemployed will specialise in job search, rather than take an interim position. If individual differences in productivity are known to the worker but not the potential employer, then search strategy may be used as a productivity signal, with more than the efficient proportion of workers searching on-the-job and too few accepting interim unskilled jobs. Optimal policy requires a subsidy on interim unskilled jobs.

In this paper we construct a model of the loss of firm-specific capital suffered by employees with occupational pensions who change job. The simplest loss function may be represented as the product of job tenure and years to retirement. Estimates of logit equations for individual job search in Great Britain suggest that the effect of pension status can be satisfactorily captured by this simple loss function. These equations and others for job turnover indicate that membership of an occupational pension scheme substantially reduces job mobility.

SummaryFor many years the principles of Delayed Auditory Feedback (D.A.F.) have been utilised: (a) in test for investigating non-organic hearing problems and (b) as a therapeutic aid to increase the oral fluency of stutterers.With reference to (a) above, if D.A.F. is to be of true value as a test for providing definitive information about the normality or otherwise, of a subject's auditory thresholds, then it is desirable that any subjective judgments of the effects on a person's voice, should be replaced by a quantifiable measure.It has been suggested that timing the reading of a passage may be useful for this purpose. Another approach is to measure the effects on the intensity of a subject's voice. A procedure was devised by the author to assess the value, if any, of the latter two measurements on a sample of 25 normally hearing subjects and on two cases with suspected non-organic hearing problems. A very clear pattern emerged for all the cases tested. It was found that if a relatively long delay time o...

IT has long been suspected that U.K. housing policy inhibits the movement of labour to growth areas, but recent evidence suggests that the council housing programme may also have influenced either the total level of unemployment, or its location. The least ambiguous evidence of such a linkage is provided in a cross-section survey of unemployment-Nickell (1980)-in which council tenants are found to be about 60% more likely to be unemployed than the average worker in other tenures holding constant various personal and occupational characteristics. The robustness of this finding remains unexplored, but in view of the accumulating evidence that council housing has substantially reduced labour mobility between areas (see e.g. Hughes and McCormick (1981)) it is perhaps unsurprising that various authors including Nickell have asked how far the higher unemployment amongst council tenants, ceteris paribus, can be explained in this way. In view of the important issues connected with this problem, further consideration of the relationship between unemployment and housing circumstance maybe helpful, and this is the purpose of the paper. Section II examines the reasons why house tenure may exert a separate influence on unemployment. Section III describes the empirical analysis. Unraveling the relationship between housing circumstance and the various aspects of unemployment is complicated by the diversity of arguments that appear a priori plausible. First, the empirical section considers how far the reported correlation between house tenure and unemployment arises incidentally because the occupations pursued by council tenants are quite different to those of owner-occupiers, with the shift dummies in Nickell's study not fully allowing for the implications of this upon unemployment. Secondly, for the housing markets in many countries it is natural to assume that job-mobile workers will prefer rental accommodation. Whereas the length of queues in Britain for unfurnished rental accommodation-which is "controlled" in the economic sense, and comprises over 90% of rental accommodation-suggest that this effect may be weaker, it remains important to ask how far higher unemployment amongst tenants reflects higher job turnover. A related point is the possibility that certain workers are more