Troubled Banks, Impaired Foreign Direct Investment: The Role of Relative Access to Credit

The relative wealth hypothesis of Froot and Stein (1991), motivated by the aggregate correlation between real exchange rates and foreign direct investment (FDI) observed in the 1980s, cannot explain one of the major shifts in FDI in the 1990s: the continued decline in Japanese FDI during a period of stable stock prices and a rapidly appreciating yen. However, when the relative wealth hypothesis is supplemented with the relative access to credit hypothesis proposed in this study, we are able to show that unequal access to credit by Japanese firms can explain the FDI puzzle in the 1990s. We utilize a unique data set that links individual Japanese firms engaged in FDI to their main banks. Using both bank-level and firm-level data sets, we find that financial difficulties at banks were economically and statistically important in reducing the number of FDI projects by Japanese firms into the United States, even after controlling for the effects associated with the relative wealth movements driven by macroeconomic fluctuations in the exchange rate and stock market prices. This provides strong empirical evidence that differences across firms in the degree of their access to credit can be an important determinant of foreign direct investment.

Design effectiveness in commercial construction.

http://archive.org/details/designeffectiven00pee

Prognostic and predictive value of circulating tumor cells and CXCR4 expression as biomarkers for a CXCR4 peptide antagonist in combination with carboplatin-etoposide in small cell lung cancer: exploratory analysis of a phase II study.

Background Circulating tumor cells (CTCs) and chemokine (C-X-C motif) receptor 4 (CXCR4) expression in CTCs and tumor tissue were evaluated as prognostic or predictive markers of CXCR4 peptide antagonist LY2510924 plus carboplatin-etoposide (CE) versus CE in extensive-stage disease small cell lung cancer (ED-SCLC). Methods This exploratory analysis of a phase II study evaluated CXCR4 expression in baseline tumor tissue and peripheral blood CTCs and in post-treatment CTCs. Optimum cutoff values were determined for CTC counts and CXCR4 expression in tumors and CTCs as predictors of survival outcome. Kaplan-Meier estimates and hazard ratios were used to determine biomarker prognostic and predictive values. Results There was weak positive correlation at baseline between CXCR4 expression in tumor tissue and CTCs. Optimum cutoff values were H-score ≥ 210 for CXCR4+ tumor, ≥7% CTCs with CXCR4 expression (CXCR4+ CTCs), and ≥6 CTCs/7.5 mL blood. Baseline H-score for CXCR4+ tumor was not prognostic of progression-free survival (PFS) or overall survival (OS). Baseline CXCR4+ CTCs ≥7% was prognostic of shorter PFS. CTCs ≥6 at baseline and cycle 2, day 1 were prognostic of shorter PFS and OS. None of the biomarkers at their respective optimum cutoffs was predictive of treatment response of LY2510924 plus CE versus CE. Conclusions In patients with ED-SCLC, baseline CXCR4 expression in tumor tissue was not prognostic of survival or predictive of LY2510924 treatment response. Baseline CXCR4+ CTCs ≥7% was prognostic of shorter PFS. CTC count ≥6 at baseline and after 1 cycle of treatment were prognostic of shorter PFS and OS

siRNA-induced immunostimulation through TLR7 promotes antitumoral activity against HPV-driven tumors in vivo

Oncogene-specific downregulation mediated by RNA interference (RNAi) is a promising avenue for cancer therapy. In addition to specific gene silencing, in vivo RNAi treatment with short interfering RNAs (siRNAs) can initiate immune activation through innate immune receptors including Toll-like receptors, (TLRs) 7 and 8. Two recent studies have shown that activation of innate immunity by addition of tri-phosphate motifs to oncogene-specific siRNAs, or by co-treatment with CpG oligos, can potentiate siRNA antitumor effects. To date, there are no reports on applying such approach against human papillomavirus (HPV)-driven cancers. Here, we characterized the antitumor effects of non-modified siRNAs that can target a specific oncogene and/or recruit the innate immune system against HPV-driven tumors. Following the characterization of silencing efficacy and TLR7 immunostimulatory potential of 15 siRNAs targeting the HPV type 16 E6/E7 oncogenes, we identified a bifunctional siRNA sequence that displayed both potent gene silencing and active immunostimulation effect. In vivo systemic administration of this siRNA resulted in reduced growth of established TC-1 tumors in C57BL/6 mice. Ablation of TLR7 recruitment via 2′O-methyl modification of the oligo backbone reduced these antitumor effects. Further, a highly immunostimulatory, but non-HPV targeting siRNA was also able to exert antitumoral effects although for less prolonged time compared with the bifunctional siRNA. Collectively, our work demonstrates for the first time that siRNA-induced immunostimulation can have antitumoral effects against HPV-driven tumors in vivo, even independent of gene silencing efficacy

Maternal super-obesity and perinatal outcomes in Australia: A national population-based cohort study

Background: Super-obesity is associated with significantly elevated rates of obstetric complications, adverse perinatal outcomes and interventions. The purpose of this study was to determine the prevalence, risk factors, management and perinatal outcomes of super-obese women giving birth in Australia. Methods: A national population-based cohort study. Super-obese pregnant women (body mass index (BMI) >50 kg/m2 or weight >140 kg) who gave birth between January 1 and October 31, 2010 and a comparison cohort were identified using the Australasian Maternity Outcomes Surveillance System (AMOSS). Outcomes included maternal and perinatal morbidity and mortality. Prevalence estimates calculated with 95 % confidence intervals (CIs). Adjusted odds ratios (ORs) were calculated using multivariable logistic regression. Results: 370 super-obese women with a median BMI of 52.8 kg/m2 (range 40.9–79.9 kg/m2) and prevalence of 2.1 per 1 000 women giving birth (95 % CI: 1.96–2.40). Super-obese women were significantly more likely to be public patients (96.2 %), smoke (23.8 %) and be socio-economically disadvantaged (36.2 %). Compared with other women, super-obese women had a significantly higher risk for obstetric (adjusted odds ratio (AOR) 2.42, 95 % CI: 1.77–3.29) and medical (AOR: 2.89, 95 % CI: 2.64–4.11) complications during pregnancy, birth by caesarean section (51.6 %) and admission to special care (HDU/ICU) (6.2 %). The 372 babies born to 365 super-obese women with outcomes known had significantly higher rates of birthweight ≥4500 g (AOR 19.94, 95 % CI: 6.81–58.36), hospital transfer (AOR 3.81, 95 % CI: 1.93–7.55) and admission to Neonatal Intensive Care Unit (NICU) (AOR 1.83, 95 % CI: 1.27–2.65) compared to babies of the comparison group, but not prematurity (10.5 % versus 9.2 %) or perinatal mortality (11.0 (95 % CI: 4.3–28.0) versus 6.6 (95 % CI: 2.6- 16.8) per 1 000 singleton births). Conclusions: Super-obesity in pregnancy in Australia is associated with increased rates of pregnancy and birth complications, and with social disadvantage. There is an urgent need to further address risk factors leading to super-obesity among pregnant women and for maternity services to better address pre-pregnancy and pregnancy care to reduce associated inequalities in perinatal outcomes. Keywords: Super-obesity, Obesity, Perinatal outcomes, Pregnancy, Maternal socio-economic disadvantage, Obstetric complication

CD44 Plays a Functional Role in Helicobacter pylori-induced Epithelial Cell Proliferation

The cytotoxin-associated gene (Cag) pathogenicity island is a strain-specific constituent of Helicobacter pylori (H. pylori) that augments cancer risk. CagA translocates into the cytoplasm where it stimulates cell signaling through the interaction with tyrosine kinase c-Met receptor, leading cellular proliferation. Identified as a potential gastric stem cell marker, cluster-of-differentiation (CD) CD44 also acts as a co-receptor for c-Met, but whether it plays a functional role in H. pylori-induced epithelial proliferation is unknown. We tested the hypothesis that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation. To assay changes in gastric epithelial cell proliferation in relation to the direct interaction with H. pylori, human- and mouse-derived gastric organoids were infected with the G27 H. pylori strain or a mutant G27 strain bearing cagA deletion (ΔCagA::cat). Epithelial proliferation was quantified by EdU immunostaining. Phosphorylation of c-Met was analyzed by immunoprecipitation followed by Western blot analysis for expression of CD44 and CagA. H. pylori infection of both mouse- and human-derived gastric organoids induced epithelial proliferation that correlated with c-Met phosphorylation. CagA and CD44 co-immunoprecipitated with phosphorylated c-Met. The formation of this complex did not occur in organoids infected with ΔCagA::cat. Epithelial proliferation in response to H. pylori infection was lost in infected organoids derived from CD44-deficient mouse stomachs. Human-derived fundic gastric organoids exhibited an induction in proliferation when infected with H. pylori, that was not seen in organoids pre-treated with a peptide inhibitor specific to CD44. In the wellestablished Mongolian gerbil model of gastric cancer, animals treated with CD44 peptide inhibitor Pep1, resulted in the inhibition of H. pylori-induced proliferation and associated atrophic gastritis. The current study reports a unique approach to study H. pylori interaction with the human gastric epithelium. Here, we show that CD44 plays a functional role in H. pyloriinduced epithelial cell proliferation

Entanglement and Timing-Based Mechanisms in the Coherent Control of Scattering Processes

The coherent control of scattering processes is considered, with electron impact dissociation of H$_2^+$ used as an example. The physical mechanism underlying coherently controlled stationary state scattering is exposed by analyzing a control scenario that relies on previously established entanglement requirements between the scattering partners. Specifically, initial state entanglement assures that all collisions in the scattering volume yield the desirable scattering configuration. Scattering is controlled by preparing the particular internal state wave function that leads to the favored collisional configuration in the collision volume. This insight allows coherent control to be extended to the case of time-dependent scattering. Specifically, we identify reactive scattering scenarios using incident wave packets of translational motion where coherent control is operational and initial state entanglement is unnecessary. Both the stationary and time-dependent scenarios incorporate extended coherence features, making them physically distinct. From a theoretical point of view, this work represents a large step forward in the qualitative understanding of coherently controlled reactive scattering. From an experimental viewpoint, it offers an alternative to entanglement-based control schemes. However, both methods present significant challenges to existing experimental technologies

Outcomes associated with transfusion in low-risk women with obstetric haemorrhage

Background and Objectives Obstetric haemorrhage is associated with increased blood transfusion, morbidity and health service usage in women. While the use of transfusion in actively bleeding patients is supported, there is little evidence for the use of blood as treatment in the nonbleeding patient following obstetric haemorrhage. Transfusion may expose women to increased morbidity. This study aims to compare outcomes between low‐risk women receiving no or 1–2 units of blood in the context of obstetric haemorrhage. Materials and Methods The study population included women giving birth in hospital in New South Wales, Australia, between July 2006 and December 2010, with a diagnosis of obstetric haemorrhage. Women with medical or obstetric conditions making them high risk were excluded, as were women receiving more than 2 units of blood. Data were obtained from linked hospital, birth and blood bank databases. Propensity score matching was used to compare outcomes between transfused and nontransfused women in order to estimate the impact of the transfusion itself on outcomes. Results There were 14989 women with obstetric haemorrhage, of whom, 1702 received a transfusion, including 1069 receiving a transfusion of 1–2 units. Women receiving transfusion were more likely to experience severe maternal morbidity (relative risk 7·0, 95% Confidence interval (2·8, 17·8)), be admitted to intensive care (RR 2·1 95% CI(1·2, 3·8)), and have a length of stay >5 days (RR 2·0, 95% CI (1·6, 2·5)). Conclusions Small volume transfusion in the context of obstetric haemorrhage among low‐risk women is associated with poorer maternal outcomes and increased healthcare utilisation.National Blood Sector Research and Development Grant. Grant Number: 105 Members of the Obstetric Transfusion Steering Group include the following: Jennifer R. Bowen, Sandra Cochrane, David O. Irving, James P. Isbister, Jonathan M. Morris, Eleni Mayson, Michael C. Nicholl, Michael J. Peek, Christine L. Roberts and Amanda Thomson. The authors thank the NSW Ministry of Health for access to the population health data and the NSW Centre for Health Record Linkage for linking the data sets

Bushfires and Mothers’ Mental Health in Pregnancy and Recent Post-Partum

Background: The compounding effects of climate change catastrophes such as bushfires and pandemics impose significant burden on individuals, societies, and their economies. The enduring effects of such syndemics on mental health remain poorly understood, particularly for at-risk populations (e.g., pregnant women and newborns). The aim of this study was to investigate the impact of direct and indirect exposure to the 2019/20 Australian Capital Territory and South-Eastern New South Wales bushfires followed by COVID-19 on the mental health and wellbeing of pregnant women and mothers with newborn babies. Methods: All women who were pregnant, had given birth, or were within three months of conceiving during the 2019/2020 bushfires, lived within the catchment area, and provided consent were invited to participate. Those who consented were asked to complete three online surveys. Mental health was assessed with the DASS-21 and the WHO-5. Bushfire, smoke, and COVID-19 exposures were assessed by self-report. Cross-sectional associations between exposures and mental health measures were tested with hierarchical regression models. Results: Of the women who participated, and had minimum data (n = 919), most (&gt;75%) reported at least one acute bushfire exposure and 63% reported severe smoke exposure. Compared to Australian norms, participants had higher depression (+12%), anxiety (+35%), and stress (+43%) scores. Women with greater exposure to bushfires/smoke but not COVID-19 had poorer scores on all mental health measures. Conclusions: These findings provide novel evidence that the mental health of pregnant women and mothers of newborn babies is vulnerable to major climate catastrophes such as bushfires.</p

Thermal Instability in Gravitationally-Stratified Plasmas: Implications for Multi-Phase Structure in Clusters and Galaxy Halos

We study the interplay among cooling, heating, conduction, and magnetic fields in gravitationally stratified plasmas using simplified, plane-parallel numerical simulations. Since the physical heating mechanism remains uncertain in massive halos such as groups or clusters, we adopt a simple, observationally-motivated prescription which enforces global thermal equilibrium when averaged over large scales. The plasma remains susceptible to local thermal instability, however, and cooling drives an inward flow of material. In contrast to previous results, we argue that the thermal stability of the plasma is independent of its convective stability. We find that the ratio of the cooling timescale to the dynamical timescale t_cool/t_ff controls the saturation of the thermal instability: when t_cool/t_ff < 1, the plasma develops extended multi-phase structure, whereas when t_cool / t_ff > 1 it does not. (In a companion paper, we show that the criterion for thermal instability in a spherical potential is somewhat less stringent, t_cool / t_ff < 10.) When thermal conduction is anisotropic with respect to the magnetic field, the criterion for multi-phase structure is essentially independent of the thermal conductivity of the plasma. Our criterion for local thermal instability to produce multi-phase structure is an extension of the cold vs. hot accretion modes in galaxy formation that applies at all radii in hot halos, not just to the virial shock. We show that this criterion is consistent with data on multi-phase gas in the ACCEPT sample of clusters; in addition, when t_cool / t_ff > 1, the net cooling rate to low temperatures and the mass flux to small radii are suppressed enough relative to models without heating to be qualitatively consistent with star formation rates and x-ray line emission in groups and clusters.Comment: This is an electronic version of an article published in Monthly Notices of the Royal Astronomical Society, Volume 419, Issue 4, pp. 3319-333