Statistical Learning, Syllable Processing, and Speech Production in Healthy Hearing and Hearing-Impaired Preschool Children: A Mismatch Negativity Study

OBJECTIVES The objectives of the present study were to investigate temporal/spectral sound-feature processing in preschool children (4 to 7 years old) with peripheral hearing loss compared with age-matched controls. The results verified the presence of statistical learning, which was diminished in children with hearing impairments (HIs), and elucidated possible perceptual mediators of speech production. DESIGN Perception and production of the syllables /ba/, /da/, /ta/, and /na/ were recorded in 13 children with normal hearing and 13 children with HI. Perception was assessed physiologically through event-related potentials (ERPs) recorded by EEG in a multifeature mismatch negativity paradigm and behaviorally through a discrimination task. Temporal and spectral features of the ERPs during speech perception were analyzed, and speech production was quantitatively evaluated using speech motor maximum performance tasks. RESULTS Proximal to stimulus onset, children with HI displayed a difference in map topography, indicating diminished statistical learning. In later ERP components, children with HI exhibited reduced amplitudes in the N2 and early parts of the late disciminative negativity components specifically, which are associated with temporal and spectral control mechanisms. Abnormalities of speech perception were only subtly reflected in speech production, as the lone difference found in speech production studies was a mild delay in regulating speech intensity. CONCLUSIONS In addition to previously reported deficits of sound-feature discriminations, the present study results reflect diminished statistical learning in children with HI, which plays an early and important, but so far neglected, role in phonological processing. Furthermore, the lack of corresponding behavioral abnormalities in speech production implies that impaired perceptual capacities do not necessarily translate into productive deficits.

L-mimosine increases the production of vascular endothelial growth factor in human tooth slice organ culture model.

AIM To assess the pro-angiogenic and pro-inflammatory capacity of the dentine-pulp complex in response to the prolyl hydroxylase inhibitor L-mimosine in a tooth slice organ culture model. METHODOLOGY Human teeth were sectioned transversely into 600-μm-thick slices and cultured in medium supplemented with serum and antibiotics. Then, pulps were stimulated for 48 h with L-mimosine. Pulps were subjected to viability measurements based on formazan formation in MTT assays. In addition, histological evaluation of pulps was performed based on haematoxylin and eosin staining. Culture supernatants were subjected to immunoassays for vascular endothelial growth factor (VEGF) to determine the pro-angiogenic capacity and to immunoassays for interleukin (IL)-6 and IL-8 to assess the pro-inflammatory response. Interleukin-1 served as pro-inflammatory control. Echinomycin was used to inhibit hypoxia-inducible factor-1 (HIF-1) alpha activity. Data were analysed using Student's t-test and Mann-Whitney U test. RESULTS Pulps within tooth slices remained vital upon L-mimosine stimulation as indicated by formazan formation and histological evaluation. L-mimosine increased VEGF production when normalized to formazan formation in the pulp tissue of the tooth slices (P < 0.05). This effect on VEGF was reduced by echinomycin (P < 0.01). Changes in normalized IL-6 and IL-8 levels upon treatment with L-mimosine did not reach the level of significance (P > 0.05), whilst treatment with IL-1, which served as positive control, increased IL-6 (P < 0.05) and IL-8 levels (P < 0.05). CONCLUSIONS The prolyl hydroxylase inhibitor L-mimosine increased VEGF production via HIF-1 alpha in the tooth slice organ culture model whilst inducing no prominent increase in IL-6 and IL-8. Pre-clinical studies will reveal if these in vitro effects translate into dental pulp regeneration.

Cigarette Smoke Exposure Increases Myeloid Cell Production and Lung Bacterial Clearance in Mice

Pneumonia is a leading cause of hospitalization in patients with chronic obstructive pulmonary disease (COPD). Although most COPD patients are smokers, the effects of cigarette smoke exposure on clearance of lung bacterial pathogens and on immune and inflammatory responses are incompletely defined. Here, clearance of Streptococcus pneumoniae and Pseudomonas aeruginosa and associated immune responses were examined in mice exposed to cigarette smoke or following smoking cessation. Mice exposed to cigarette smoke for 6 weeks or 4 months demonstrated decreased lung bacterial burden compared to air-exposed mice when infected 16-24 hours post-exposure. When infection was performed after smoke cessation, bacterial clearance kinetics of mice previously exposed to smoke reversed to comparable levels as those of control mice suggesting that the observed defects were not dependent on adaptive immunological memory to bacterial determinants found in smoke. Comparing cytokine levels and myeloid cell production prior to infection in mice exposed to cigarette smoke relative to mice never exposed or following smoke cessation revealed that reduced bacterial burden was most strongly associated with higher levels of IL-1β and GM-CSF in the lungs and with increased neutrophil reserve and monocyte turnover in the bone marrow. Using serpinb1a-deficient mice with reduced neutrophil numbers and treatment with G-CSF showed that increased neutrophil numbers contribute only in part to the effect of smoke on infection. Our findings indicate that cigarette smoke induces a temporary and reversible increase in clearance of lung pathogens, which correlates with local inflammation and increased myeloid cell output from the bone marrow.

Promoting palliative care in the community: production of the primary palliative care toolkit by the European Association of Palliative Care Taskforce in primary palliative care

BACKGROUND A multidisciplinary European Association of Palliative Care Taskforce was established to scope the extent of and learn what facilitates and hinders the development of palliative care in the community across Europe. AIM To document the barriers and facilitators for palliative care in the community and to produce a resource toolkit that palliative care specialists, primary care health professionals or policymakers, service developers, educationalists and national groups more generally could use to facilitate the development of palliative care in their own country. DESIGN (1) A survey instrument was sent to general practitioners with knowledge of palliative care services in the community in a diverse sample of European countries. We also conducted an international systematic review of tools used to identify people for palliative care in the community. (2) A draft toolkit was then constructed suggesting how individual countries might best address these issues, and an online survey was then set up for general practitioners and specialists to make comments. Iterations of the toolkit were then presented at international palliative care and primary care conferences. RESULTS Being unable to identify appropriate patients for palliative care in the community was a major barrier internationally. The systematic review identified tools that might be used to help address this. Various facilitators such as national strategies were identified. A primary palliative care toolkit has been produced and refined, together with associated guidance. CONCLUSION Many barriers and facilitators were identified. The primary palliative care toolkit can help community-based palliative care services to be established nationally.

Higher macrophage superoxide anion production in coronary artery disease (CAD) patients with Type D personality

BACKGROUND Type D personality (Type D) is an independent psychosocial risk factor for poor cardiac prognosis and increased mortality in patients with cardiovascular disease (CVD), but the involved mechanisms are poorly understood. Macrophages play a pivotal role in atherosclerosis, the process underlying coronary artery disease (CAD). We investigated macrophage superoxide anion production in production in CAD patients with and without Type D. METHODS AND RESULTS We studied 20 male CAD patients with Type D (M:66.7±9.9years) and 20 age-matched male CAD patients without Type D (M:67.7±8.5years). Type D was measured using the DS14 questionnaire with the two subscales 'negative affectivity' and 'social inhibition'. We assessed macrophage superoxide anion production using the WST-1 assay. All analyses were controlled for potential confounders. CAD patients with Type D showed higher superoxide anion production compared to CAD patients without Type D (F(1,38)=15.57, p<0.001). Complementary analyses using the Type D subscales 'negative affectivity' and 'social inhibition', and their interaction as continuous measures, showed that both Type D subscales (negative affectivity: (ß=0.48, p=0.002, R(2)=0.227); social inhibition: (ß=0.46, p=0.003, R(2)=0.208)) and their interaction (ß=0.36, p=0.022, R(2)=0.130) were associated with higher WST-1 reduction scores. Results remained significant when controlling for classical CVD risk factors (i.e. body mass index, mean arterial blood pressure), atherosclerosis severity (i.e. intima media thickness, presence of carotid plaques), and psychological factors (depressive symptom severity, chronic stress). CONCLUSIONS Our results indicate higher macrophage superoxide anion production in CAD patients with Type D compared to those without Type D. This may suggest a mechanism contributing to increased morbidity and mortality in CAD patients with Type D.

The roles of costimulatory molecules in the cooperative effects of combination epinephrine and dexamethasone on type-1/type-2 cytokine production in tetanus-toxoid specific stimulated human peripheral blood mononuclear cells

A growing number of studies show strong associations between stress and altered immune function. In vivo studies of chronic and acute stress have demonstrated that cognitive stressors are strongly correlated with high circulating levels of catecholamines (CT) and corticosteroids (CS) that are associated with changes in type-1/type-2 cytokine expression. Although individual pharmacologic doses of CS and CT can inhibit the expression of T-helper 1 (Th1, type-1 like) and promote the production of T-helper 2 (Th2, type-2 like) cytokines in antigen-specific and mitogen stimulated human leukocyte cultures in vitro, little attention has been focused on the effects of combination physiologic-stress doses of CT and CS that may be more physiologically relevant. In addition, both in-vivo and in-vitro studies suggest that the differential expression of the B7 family of costimulatory molecules CD80 and CD86 may promote the expression of type-1 or type-2 cytokines, respectively. Furthermore, corticosteroids can influence the expression of β2-adrenergic receptors in various human tissues. We therefore investigated the combined effects of physiologic-stress doses of in vitro CT and CS upon the type-1/type-2 cytokine balance and expression of B7 costimulatory molecules of human peripheral blood mononuclear cells (PBMC) as a model to study the immunomodulatory effects of physiologic stress. Results demonstrated a significant decrease in type-1 cytokine expression and a significant increase in type-2 cytokine production in our CS+CT incubated cultures when compared to either CT or CS agents alone. In addition, we demonstrated the differential expression of CD80/CD86 in favor of CD86 at the cellular and population level as determined by flow cytometry in lipopolysaccharide stimulated human Monocytes. Furthermore, we developed flow cytometry based assays to detect total β2AR in human CD4+ T-lymphocytes that demonstrated decreased expression of β2AR in mitogen stimulated CD4+ T-lymphocytes in the presence of physiologic stress levels of CS and CT as single in vitro agents, however, when both CS and CT were combined, significantly higher expression of β2AR was observed. In summary, our in vitro data suggest that both CS and CT work cooperatively to shift immunity towards type-2 responses. ^

The role of MEKK3 in T cell homeostasis and IFNgamma production

MEKK3, a member of the MAP3K family, is involved in regulating multiple MAPK and NF-κB pathways. The MAPK and NF-κB signaling pathways are important in regulating T cell functions. MEKK3 is expressed through the development of T cell and also in subsets of T cell in the peripheral. However, the specific role of MEKK3 in T cell function is unknown. To reveal the in vivo function of MEKK3 in T cells, I have generated MEKK3 T cell conditional knock-out mice. Despite a normal thymus development in the conditional knock-out mice, I observed a decrease in the number of peripheral T-cells and impaired T-cell function in response to antigen stimulation. T cells undergo homeostatic proliferation under lymphopenia condition, a process called lymphopenia-induced proliferation (LIP). Using a LIP model, I demonstrated that the reduction of peripheral T cell number is largely due to a severe impairment of the self-antigen/MHC mediated T cell homeostasis. Upon anti-CD3 stimulation, the proliferation of MEKK3-deficient T cell is not significantly affected, but the production of IFNγ by naïve and effector CD4 T cells are markedly decreased. Interestingly, the IL-12/IL-18 driven IFNγ production and MAPK activation in MEKK3-deficient T cells is not affected, suggesting that MEKK3 selectively mediates the TCR induced MAPK signaling. Furthermore, I found that MEKK3 is activated by TCR stimulation in a RAC1/2 dependent manner, but not by IL-12/IL-18 stimulation. Finally, I showed that basal level of ERK and JNK activation is defective under LIP condition. I showed that the TCR induced ERK, JNK and p38 MAPK activation is also defective in MEKK3 deficient CD4 T cells. Taken together, my data demonstrate a crucial role of MEKK3 in T cell homeostasis and IFNγ production through regulating the TCR mediated MAPK pathway. ^

Effects of asbestos and silica on superoxide anion production in the guinea pig alveolar macrophage

Asbestos and silica are important industrial hazards. Exposure to these dusts can result in pulmonary fibrosis and, in the case of asbestos, cancer. Although the hazards of asbestos and silica exposure have long been known, the pathogenesis of dust-related disease is not well understood. Both silica and asbestos are thought to alter the function of the alveolar macrophage, but the nature of the biochemical alteration is unknown. Therefore, this study examined the effect of asbestos and silica on the activation pathway of the guinea pig alveolar macrophage. Activation of macrophages by physiological agents results in stimulation of phospholipase C causing phosphatidyl inositol turnover and intracellular calcium mobilization. Phosphatidyl inositol turnover produces diacylglycerol which activates protein kinase C causing superoxide anion production.^ Chrysotile stimulated alveolar macrophages to produce superoxide anion. This stimulation proceeded via phospholipase C, since chrysotile stimulated phosphatidyl inositol turnover and intracellular calcium mobilization. The possible involvement of a coupling protein was evaluated by pretreating cells with pertussis toxin. Pertussis toxin pretreatment partially inhibited chrysotile stimulation, suggesting that chrysotile activates a coupling protein in an non-classical manner. Potential binding sites for chrysotile stimulation were examined using a series of nine lectins. Chrysotile-stimulated superoxide anion production was blocked by pretreatment with lectins which bound to N-acetylglucosamine, but not by lectins which bound to mannose, fucose, or N-acetylgalactosamine. In addition, incubation with the N-acetylglucosamine polymer, chitin, inhibited chrysotile-stimulated superoxide anion production, suggesting that chrysotile stimulated superoxide anion production by binding to N-acetylglucosamine residues.^ On the other hand, silica did not stimulate superoxide anion production. The effect of silica on agonist stimulation of this pathway was examined using two stimulants of superoxide anion production, N-formyl-nle-leu-phe (FNLP, which stimulates through phospholipase C) and phorbol-12,13-dibutyrate (which directly activates protein kinase C). Sublethal doses of silica inhibited FNLP-stimulated superoxide anion production, but did not affect phorbol-12,13-dibutyrate-stimulated superoxide anion production, suggesting that the site of inhibition precedes protein kinase C. This inhibition was not due to cell membrane damage, since cell permeability to calcium-45 and rubidium-86 was not increased. It is concluded that chrysotile binds to N-acetylglucosamine residues on macrophage surface glycoproteins to stimulate the physiological pathway resulting in superoxide anion production. In contrast, silica does not stimulate superoxide anion production, but it did inhibit FNLP-stimulated superoxide anion production. ^

DIAGNOSTIC ANTIGENS FOR SCHISTOSOMIASIS MANSONI: PRODUCTION, CHARACTERIZATION AND PURIFICATION OF MONOCLONAL ANTIBODIES, AND AFFINITY PURIFICATION OF ANTIGENS

Attempts have been made in this dissertation to develop a purified antigen with high sensitivity and specificity for diagnosis of Schistosoma mansoni (Sm) infection by using the hybridoma technique.^ Spleen cells, obtained from mice immunized by infection with Sm and boosted by cercarial antigens, or by injection of circulating antigen (CA) in serum from infected mice, were fused with Sp2/0 myeloma cells. The active infection resulted a higher number of hybridomas (100%) than by CA (20%), and higher levels of antibody reactivity as measured by ELISA.^ The IgM and IgG monoclonal antibodies (MCAbs) were purified respectively by gel filtration, DE 52 ion exchange column and proteinase A affinity column. The cercarial and egg antigens were purified by affinity chromatography through MCAb/affi-gel column. The reactivity of the purified antigens were then monitored by ELISA, SDS-PAGE silver stain and EITB.^ The respective MCAbs recognized varying antigenic determinants (AD) present in adult, cercaria and egg stages. By EITB the MCAbs IgM and IgG, when reacted with nine antigens from the various stages, revealed identical bands, suggesting that the two MCAb classes originated from identical AD. By ELISA and COPT, the MCAbs from thirteen cell lines gave same results. But by CHR, two MCAbs showed negative results while eleven other MCAbs showed strong positive. It is assumed that the AD in the immunogen that ilicited the MCAbs were immunochemically closely related.^ One egg purified by immunoaffinity indicated that the epitopes recognized by MCAb were present on four antigenic components with molecular weights (Mr) of approximately 19, 25, 60 and >224 kd, respectively. By EITB the Mr 19 doublet appeared to be species specific; the Mr 25 kd genus specific. They reacted with mouse serum from 13-16 weeks after infection. In monkey serum Mr 19 doublet appeared 8-10 weeks after infection and disappeared at 8-12 weeks after Droncit treatment, paralleled to the disappearance of fecal egg. The Mr 60 and >224 kd bands were also demonstrated with S. japonicum, S. haematobium and Trichinella spiralis infection sera and may be the cause of cross-reaction in conventional serological test. ^

HEALTH CARE COST INCREASES IN METROPOLITAN AREAS

The research project is an extension of the economic theory to the health care field and health care research projects evaluating the influence of demand and supply variables upon medical care inflation. The research tests a model linking the demographic and socioeconomic characteristics of the population, its community case mix, and technology, the prices of goods and services other than medical care, the way its medical services are delivered and the health care resources available to its population to different utilization patterns which, consequently, lead to variations in health care prices among metropolitan areas. The research considers the relationship of changes in community characteristics and resources and medical care inflation.^ The rapidly increasing costs of medical care have been of great concern to the general public, medical profession, and political bodies. Research and analysis of the main factors responsible for the rate of increase of medical care prices is necessary in order to devise appropriate solutions to cope with the problem. An understanding of the community characteristics and resources-medical care costs relationships in the metropolitan areas potentially offers guidance in individual plan and national policy development.^ The research considers 145 factors measuring community milieu (demographic, social, educational, economic, illness level, prices of goods and services other than medical care, hospital supply, physicians resources and techological factors). Through bivariate correlation analysis, the number of variables was reduced to a set of 1 to 4 variables for each cost equation. Two approaches were identified to track inflation in the health care industry. One approach measures costs of production which accounts for price and volume increases. The other approach measures price increases. One general and four specific measures were developed to represent each of the major approaches. The general measure considers the increase on medical care prices as a whole and the specific measures deal with hospital costs and physician's fees. The relationships among changes in community characteristics and resources and health care inflation were analyzed using bivariate correlation and regression analysis methods. It has been concluded that changes in community characteristics and resources are predictive of hospital costs and physician's fees inflation, but are not predictive of increases in medical care prices. These findings provide guidance in the formulation of public policy which could alter the trend of medical care inflation and in the allocation of limited Federal funds.^

Chronic stress promotes tumor growth through increased BDNF production and neo-innervation

Background: Activation of the sympathetic nervous system (SNS) in response to chronic biobehavioral stress results in high levels of catecholamines and persistent activation of adrenergic signaling, which promotes tumor growth and progression. However it is unknown how catecholamine levels within the tumor exceed systemic levels in circulation. I hypothesized that neo-innervation of tumors is required for stress-mediated effects on tumor growth. Results: First, I examined whether sympathetic nerves are present in human ovarian cancer samples as well as orthotopic ovarian cancer models. Immunohistochemical (IHC) staining for neurofilament revealed that catecholaminergic neurons are present within tumor tissue. In order to determine whether chronic stress affects the density of nerves in the tumor, I utilized an orthotopic mouse model of ovarian cancer that was exposed to daily restraint stress. IHC analysis revealed that nerve density in tumors increased by more than three-fold in stressed animals versus non-stressed controls. IHC analysis suggested that this results from both recruitment of existing neurons (axonogenesis) as well as new neuron formation (neurogenesis) within the tumor. To determine how tumors are recruiting nerve growth, I utilized a PCR array analysis of 84 nerve growth related genes and their receptors, which showed that stimulation of the SKOV3 ovarian cancer cell line with norepinephrine (NE) leads to increased expression of several neurotrophins, including brain-derived neurotrophic factor (BDNF). Neurite extension assays showed that media conditioned by ovarian cancer cell lines is capable of inducing neurite outgrowth in differentiated neuron-like PC12 cells, and NE treatment of cancer cells potentiates this effect. Norepinephrine-induced neurite extension was abolished after BDNF silencing by siRNA, suggesting that BDNF is critical to tumor cell-induced nerve growth. in vivo BDNF inhibition resulted in complete abrogation of stress-induced increases in tumor weight and nerve density, as well as downstream markers of stress. Discussion: These studies indicate that adrenergic signalling induced by chronic stress promotes neo-innervation in the tumor microenvironment. This results in a mutually beneficial relationship between the tumor cells and neurons. This work is crucial for providing a link between chronic stress and its effects on the tumor and its microenvironment. The data shown here aims to open new venues that can be used in development of therapies designed to block the stress effects on tumor growth.

NOVEL INDUCERS OF GLIOTOXIN PRODUCTION IN ASPERGILLUS FUMIGATUS

Secondary metabolites are produced by numerous organisms and can either be benign to humans or harmful. Genes involved in the synthesis and transport of these secondary metabolites are frequently found in gene clusters, which are often located in subtelomeric regions of the chromosome. These clusters are often coordinately regulated, being almost exclusively dependent on transcription factors that are located within the clusters themselves. Secondary metabolites are also regulated by a variety of factors, including nutritional factors, environmental factors and developmental processes. Gliotoxin, which is produced by a variety of Aspergillus species, Trichoderma species, and Penicillium species, exhibits immunosuppressive properties and has therefore been the subject of research for many laboratories. There have been a few proteins shown to regulate the gliotoxin cluster, most notably GliZ, a Zn2Cys6 binuclear finger transcription factor that lies within the cluster, and LaeA, a putative methyltransferase that globally regulates secondary metabolism clusters within numerous fungal organisms, although no study has demonstrated the direct binding of any protein to a promoter region in the gliotoxin cluster. I report here two novel proteins, GipA, a C2H2 transcription factor and GipB, a hybrid sensor kinase, which are involved in regulating the gliotoxin biosynthetic cluster. GipA plays an important role in gliotoxin production, as high-copy expression of gipA induces gliotoxin biosynthesis and loss of gipA reduces gliotoxin biosynthesis by 50%. GipB is also involved in regulating gliotoxin production, as high-copy expression of gipB induces gliotoxin biosynthesis, but only during certain stages of asexual development. Furthermore, loss of gipB reduces gliotoxin biosynthesis by 10%. Based on data obtained from this project, I propose a model for the regulation of gliA, the efflux pump of the gliotoxin cluster, which involves GipB signaling through both GliZ and GipA. I propose that GliZ and GipA are interdependent, as mutation of the GipA DNA binding site in the gliA promoter negatively affects both GliZ-mediated and GipA-mediated induction of gliA. This is further supported by the fact that GliZ cannot fully induce gliA in the absence of GipA and vice versa. This is the first time that anyone has shown evidence of a protein directly binding to the gliotoxin cluster. Even though biosynthetic clusters are often coordinately regulated, my model raises the possibility that gliA is independently regulated, as the layout of the binding site in the gliA promoter is not present upstream of any other genes in the gliotoxin cluster, except for gliZ.

Health care providers' opinions on abortion: a study for the implementation of the legal abortion public policy in the Province of Santa Fe, Argentina

Background: In Argentina, abortion has been decriminalized under certain circumstances since the enactment of the Penal Code in 1922. Nevertheless, access to abortion under this regulatory framework has been extremely limited in spite of some recent changes. This article reports the findings of the first phase of an operations research study conducted in the Province of Santa Fe, Argentina, regarding the implementation of the local legal and safe abortion access policy. Methods: The project combined research and training to generate a virtuous circle of knowledge production, decision-making, and the fostering of an informed healthcare policy. The project used a pre-post design of three phases: baseline, intervention, and evaluation. It was conducted in two public hospitals. An anonymous self-administered questionnaire (n = 157) and semi-structured interviews (n = 27) were applied to gather information about tacit knowledge about the regulatory framework; personal opinions regarding abortion and its decriminalization; opinions on the requirements needed to carry out legal abortions; and service’s responses to women in need of an abortion. Results: Firstly, a fairly high percentage of health care providers lack accurate information on current legal framework. This deficit goes side by side with a restrictive understanding of both health and rape indications. Secondly, while a great majority of health care providers support abortion under the circumstances consider in the Penal Code, most of them are reluctant towards unrestricted access to abortion. Thirdly, health care providers’ willingness to perform abortions is noticeably low given that only half of them are ready to perform an abortion when a woman’s life is at risk. Willingness is even lower for each of the other current legal indications. Conclusions: Findings suggest that there are important challenges for the implementation of a legal abortion policy. Results of the study call for specific strategies targeting health care providers in order to better inform about current legal abortion regulations and to sensitize them about abortion social determinants. The interpretation of the current legal framework needs to be broadened in order to reflect a comprehensive view of the health indication, and stereotypes regarding women’s sexuality and abortion decisions need to be dismantled.

Ocean acidification induces multi-generational decline in copepod naupliar production with possible conflict for reproductive resource allocation

Climate change, including ocean acidification (OA), presents fundamental challenges to marine biodiversity and sustained ecosystem health. We determined reproductive response (measured as naupliar production), cuticle composition and stage specific growth of the copepod Tisbe battagliai over three generations at four pH conditions (pH 7.67, 7.82, 7.95, and 8.06). Naupliar production increased significantly at pH 7.95 compared with pH 8.06 followed by a decline at pH 7.82. Naupliar production at pH 7.67 was higher than pH 7.82. We attribute the increase at pH 7.95 to an initial stress response which was succeeded by a hormesis-like response at pH 7.67. A multi-generational modelling approach predicted a gradual decline in naupliar production over the next 100 years (equivalent to approximately 2430 generations). There was a significant growth reduction (mean length integrated across developmental stage) relative to controls. There was a significant increase in the proportion of carbon relative to oxygen within the cuticle as seawater pH decreased. Changes in growth, cuticle composition and naupliar production strongly suggest that copepods subjected to OA-induced stress preferentially reallocate resources towards maintaining reproductive output at the expense of somatic growth and cuticle composition. These responses may drive shifts in life history strategies that favour smaller brood sizes, females and perhaps later maturing females, with the potential to profoundly destabilise marine trophodynamics.

Fiscal Decentralization, Chinese Style: Good for Health Outcomes?

This study analyzes the effect of fiscal decentralization on health outcomes in China using a panel data set with nationwide county-level data. We find that counties in more fiscal decentralized provinces have lower infant mortality rates compared to those counties in which the provincial government retains the main spending authority, if certain conditions are met. Spending responsibilities at the local level need to be matched with county government's own fiscal capacity. For those local governments that have only limited revenues, their ability to spend on local public goods such as health care depends crucially upon intergovernmental transfers. The findings of this study thereby support the common assertion that fiscal decentralization can indeed lead to more efficient production of local public goods, but also highlights the necessary conditions to make this happen.