Inequities in the physical activity of disabled young people in Aotearoa New Zealand: a stakeholder SWOT analysis of the physical activity sector.

AIMS: Disabled people, particularly children and adolescents, tend to participate in less physical activity than their non-disabled peers on average. However, disabled children and youth (i.e., young people [YP]) are typically underrepresented in physical activity (PA) research, with little data available in Aotearoa New Zealand to guide policy makers to alter societal factors that contribute to disability inequities. The purpose of this study was to conduct a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis of the PA sector in Aotearoa New Zealand with respect to PA participation and promotion among disabled YP. METHODS: Focus group discussions, underpinned by the SWOT framework, were facilitated with stakeholders (n=11) engaged in the Aotearoa New Zealand PA sector. Data were transcribed and analysed using content analysis. Desirable and accessible opportunities were essential enablers of PA in disabled YP. RESULTS: Communication, transport, equipment costs, awareness of activities, and social support were identified as factors that influence PA participation. Schools also have a considerable influence on PA participation among disabled YP, while greater funding for and cohesion/collaboration among PA providers is key to continued growth in PA participation. CONCLUSIONS: Communication, accessibility, funding, and collaborative/coordinated multi-level efforts were identified as areas in need of strengthening to provide equitable opportunities for disabled YP in Aotearoa New Zealand to participate in PA.

Distinguishing Constraints on Financial Inclusion and Their Impact on GDP, TFP, and the Distribution of Income.

A general equilibrium model featuring multiple realistic sources of financial frictions is developed to study how different constraints interact in equilibrium. We highlight, distinguish, and evaluate their differential impacts and rich interactions. The economic impact of financial inclusion policies in an economy depends not only on which constraint is alleviated, but also on the tightness of other constraints. Policy instruments should target the most binding constraint, which likely varies across countries. Moreover, there are important tradeoffs between financial inclusion, GDP, and the distribution of income. The transitional dynamics also differ from those in steady states. Policy makers should consider both.

Revision total elbow arthroplasty: Is it safe to perform a single-stage revision for presumed aseptic loosening based on clinical assessment, normal inflammatory markers, and a negative aspiration?

BACKGROUND: Revision total elbow arthroplasty (TEA) is a challenging procedure that is becoming increasingly common. In our unit, we regard it as essential to exclude infection as the underlying cause of TEA loosening. In all patients with arthroplasty loosening, we undertake a careful history and examination, perform radiographs, monitor inflammatory markers, and undertake a joint aspiration. If any investigation suggests infection as the etiology, then a 2-stage revision is undertaken. Open biopsies are not routinely performed. The aim was to ascertain from our outcomes whether it is safe to perform a single-stage revision for presumed aseptic loosening using these criteria. METHODS: A retrospective review of a consecutive series of revision TEAs was performed in our unit over a 10-year period (2008-2018). Single-stage revisions performed for presumed aseptic loosening were identified. Case notes, radiographs, bloods, aspiration results, and microbiology of tissue samples taken at revision were reviewed. RESULTS: A total of 123 revision elbow arthroplasty cases were performed in the study period. Sixty cases were revised for preoperatively proven infection, instability, or implant failure and were excluded from this study. In 63 cases, aseptic loosening was diagnosed based on history, clinical examination, blood markers, and aspiration. There were 21 dual-component and 42 single-component revisions. In the dual-component revision group, tissue samples taken at the time of revision were positive in only 1 case (5%). In the single-component revision group, positive culture samples were present in 3 cases (7%). χ2 analysis showed no significant difference between single- and dual-component revisions (P = .76). No cases with positive culture samples from either group have required subsequent revision surgery. CONCLUSION: Given the results of this study, we conclude that is safe to perform single-stage revision arthroplasty for implant loosening based on history, examination, normal inflammatory markers, and negative aspiration results without the need for open biopsy.

FAMILY FIRMS, BANK RELATIONSHIPS, AND FINANCIAL CONSTRAINTS: A COMPREHENSIVE SCORE CARD.

We examine the effect of financial constraints on firm investment and cash flow. We combine data from the Spanish Mercantile Registry and the Bank of Spain Credit Registry to classify firms according to whether they are family-owned, not family-owned, or belong to a family-linked network of firms and according to their number of banking relations (with none, one, or several banks). Our empirical strategy is structural, based on a dynamic model solved numerically to generate the joint distribution of firm capital (size), investment and cash flow, both in cross-sections and in panel data. We consider three alternative financial settings: saving only, borrowing and lending, and moral hazard constrained state-contingent credit. We estimate each setting via maximum likelihood and compare across these financial regimes. Based on the estimated financial regime, we show that family firms, especially those belonging to networks based on ownership, are associated with a more flexible market or contract environment and are less financially constrained than non-family firms. This result survives stratifications of family and non-family firms by bank status, region, industry and time period. Family firms are better able to allocate funds and smooth investment across states of the world and over time, arguably done informally or using the cash flow generated at the level of the network. We also validate our structural approach by demonstrating that it performs well in traditional categories, by stratifying firms by size and age and find that smaller and younger firms are more constrained than larger and older firms.

Risk and Return in Village Economies.

This paper provides a theory-based empirical framework for understanding the risk and return on productive capital assets and their allocation across activities in an economy characterized by idiosyncratic and aggregate risk and thin formal markets for real and financial assets. We apply our framework to households running business enterprises in Thai villages with extensive networks, taking advantage of panel data: income, assets, consumption, gifts, and loans. We decompose risk and estimate the risk premia faced by households, distinguishing aggregate risk from idiosyncratic, potentially diversifiable risk. This distinction matters for estimating measures of underlying productivity and has important policy implications.

Integrated Household Surveys: An Assessment of U.S. Methods and an Innovation.

We present a vision for improving household financial surveys by integrating responses from questionnaires more completely with financial statements and combining them with payments data from diaries. Integrated household financial accounts-balance sheet, income statement, and statement of cash flows-are used to assess the degree of integration in leading U.S. household surveys, focusing on inconsistencies in measures of the change in cash. Diaries of consumer payment choice can improve dynamic integration. Using payments data, we construct a statement of liquidity flows: a detailed analysis of currency, checking accounts, prepaid cards, credit cards, and other payment instruments, consistent with conventional cash-flows measures and the other financial accounts.

Economic development, flow of funds, and the equilibrium interaction of financial frictions.

We use a variety of different datasets from Thailand to study not only the extremes of micro and macro variables but also within-country flow of funds and labor migration. We develop a general equilibrium model that encompasses regional variation in the type of financial friction and calibrate it to measured variation in regional aggregates. The model predicts substantial capital and labor flows from rural to urban areas even though these differ only in the underlying financial regime. Predictions for micro variables not used directly provide a model validation. Finally, we estimate the impact of a policy of counterfactual, regional isolationism.

Pharmacokinetic Assessment of Drug-Drug Interactions of Isavuconazole With the Immunosuppressants Cyclosporine, Mycophenolic Acid, Prednisolone, Sirolimus, and Tacrolimus in Healthy Adults.

This report summarizes phase 1 studies that evaluated pharmacokinetic interactions between the novel triazole antifungal agent isavuconazole and the immunosuppressants cyclosporine, mycophenolic acid, prednisolone, sirolimus, and tacrolimus in healthy adults. Healthy subjects received single oral doses of cyclosporine (300 mg; n = 24), mycophenolate mofetil (1000 mg; n = 24), prednisone (20 mg; n = 21), sirolimus (2 mg; n = 22), and tacrolimus (5 mg; n = 24) in the presence and absence of clinical doses of oral isavuconazole (200 mg 3 times daily for 2 days; 200 mg once daily thereafter). Coadministration with isavuconazole increased the area under the concentration-time curves (AUC0-∞ ) of tacrolimus, sirolimus, and cyclosporine by 125%, 84%, and 29%, respectively, and the AUCs of mycophenolic acid and prednisolone by 35% and 8%, respectively. Maximum concentrations (Cmax ) of tacrolimus, sirolimus, and cyclosporine were 42%, 65%, and 6% higher, respectively; Cmax of mycophenolic acid and prednisolone were 11% and 4% lower, respectively. Isavuconazole pharmacokinetics were mostly unaffected by the immunosuppressants. Two subjects experienced elevated creatinine levels in the cyclosporine study; most adverse events were not considered to be of clinical concern. These results indicate that isavuconazole is an inhibitor of cyclosporine, mycophenolic acid, sirolimus, and tacrolimus metabolism.

Human Capital Acquisition and Occupational Choice: Implications for Economic Development.

Using household-level data from Mexico we document patterns among schooling, entrepreneurial decisions and household characteristics such as assets, talent of household members and age of the household head. Motivated by our findings, we develop a heterogeneous-agent, incomplete-markets, overlapping-generations dynasty model. Households jointly decide over their life cycle on (i) kids' human capital investments (schooling) and (ii) parents' entry, exit and investment into alternative entrepreneurial modes (subsistence and modern). With financial constraints all of these are co-determined. A calibrated version of our model can account for the broad correlation patterns uncovered in the data within and across generations, e.g., a non-monotonic relationship between educational choices and assets across occupations, growth in profits and employment for modern firms only, and dynastic persistence across generations in education and wealth. Endogenous human capital acquisition is a key driver of inequality and intergenerational persistence. Eliminating this channel would decrease the top 10% income share by 47%. Eliminating within-period borrowing constraints would increase average household expenditure by 7.1% and benefit the middle class, reducing top and bottom expenditure shares. It would also reduce by 28% the correlation between household assets and kids' schooling levels.

Population Pharmacokinetics of Isavuconazole from Phase 1 and Phase 3 (SECURE) Trials in Adults and Target Attainment in Patients with Invasive Infections Due to Aspergillus and Other Filamentous Fungi.

Isavuconazole, the active moiety of the water-soluble prodrug isavuconazonium sulfate, is a triazole antifungal agent used for the treatment of invasive fungal infections. The objective of this analysis was to develop a population pharmacokinetic (PPK) model to identify covariates that affect isavuconazole pharmacokinetics and to determine the probability of target attainment (PTA) for invasive aspergillosis patients. Data from nine phase 1 studies and one phase 3 clinical trial (SECURE) were pooled to develop the PPK model (NONMEM, version 7.2). Stepwise covariate modeling was performed in Perl-speaks-NONMEM, version 3.7.6. The area under the curve (AUC) at steady state was calculated for 5,000 patients by using Monte Carlo simulations. The PTA using the estimated pharmacodynamic (PD) target value (total AUC/MIC ratio) estimated from in vivo PD studies of invasive aspergillosis over a range of MIC values was calculated using simulated patient AUC values. A two-compartment model with a Weibull absorption function and a first-order elimination process adequately described plasma isavuconazole concentrations. The mean estimate for isavuconazole clearance was 2.360 liters/h (percent coefficient of variation [%CV], 34%), and the mean AUC from 0 to 24 h (AUC0-24) was ∼100 mg·h/liter. Clearance was approximately 36% lower in Asians than in Caucasians. The PTA calculated over a range of MIC values by use of the nonneutropenic murine efficacy index corresponding to 90% survival indicated that adequate isavuconazole exposures were achieved in >90% of simulated patients to treat infections with MICs up to and including 1 mg/liter according to European Committee on Antimicrobial Susceptibility Testing methodology and in >90% of simulated patients for infections with MICs up to and including 0.5 mg/liter according to Clinical and Laboratory Standards Institute methodology. The highest MIC result for PTA was the same for Caucasian and Asian patients.

An Evaluation of Financial Institutions: Impact on Consumption and Investment Using Panel Data and the Theory of Risk-Bearing.

The theory of the optimal allocation of risk and the Townsend Thai panel data on financial transactions are used to assess the impact of the major formal and informal financial institutions of an emerging market economy. We link financial institution assessment to the actual impact on clients, rather than ratios and non-performing loans. We derive both consumption and investment equations from a common core theory with both risk and productive activities. The empirical specification follows closely from this theory and allows both OLS and IV estimation. We thus quantify the consumption and investment smoothing impact of financial institutions on households including those running farms and small businesses. A government development bank (BAAC) is shown to be particularly helpful in smoothing consumption and investment, in no small part through credit, consistent with its own operating system, which embeds an implicit insurance operation. Commercial banks are smoothing investment, largely through formal savings accounts. Other institutions seem ineffective by these metrics.

Dynamic Financial Constraints: Distinguishing Mechanism Design from Exogenously Incomplete Regimes.

We formulate and solve a range of dynamic models of constrained credit/insurance that allow for moral hazard and limited commitment. We compare them to full insurance and exogenously incomplete financial regimes (autarky, saving only, borrowing and lending in a single asset). We develop computational methods based on mechanism design, linear programming, and maximum likelihood to estimate, compare, and statistically test these alternative dynamic models with financial/information constraints. Our methods can use both cross-sectional and panel data and allow for measurement error and unobserved heterogeneity. We estimate the models using data on Thai households running small businesses from two separate samples. We find that in the rural sample, the exogenously incomplete saving only and borrowing regimes provide the best fit using data on consumption, business assets, investment, and income. Family and other networks help consumption smoothing there, as in a moral hazard constrained regime. In contrast, in urban areas, we find mechanism design financial/information regimes that are decidedly less constrained, with the moral hazard model fitting best combined business and consumption data. We perform numerous robustness checks in both the Thai data and in Monte Carlo simulations and compare our maximum likelihood criterion with results from other metrics and data not used in the estimation. A prototypical counterfactual policy evaluation exercise using the estimation results is also featured.

Heterogeneity and Risk Sharing in Village Economies.

We show how to use panel data on household consumption to directly estimate households' risk preferences. Specifically, we measure heterogeneity in risk aversion among households in Thai villages using a full risk-sharing model, which we then test allowing for this heterogeneity. There is substantial, statistically significant heterogeneity in estimated risk preferences. Full insurance cannot be rejected. As the risk sharing, as-if-complete-markets theory might predict, estimated risk preferences are unrelated to wealth or other characteristics. The heterogeneity matters for policy: Although the average household would benefit from eliminating village-level risk, less-risk-averse households who are paid to absorb that risk would be worse off by several percent of household consumption.

Barriers to Household Risk Management: Evidence from India.

Why do many households remain exposed to large exogenous sources of non-systematic income risk? We use a series of randomized field experiments in rural India to test the importance of price and non-price factors in the adoption of an innovative rainfall insurance product. Demand is significantly price sensitive, but widespread take-up would not be achieved even if the product offered a payout ratio comparable to U.S. insurance contracts. We present evidence suggesting that lack of trust, liquidity constraints and limited salience are significant non-price frictions that constrain demand. We suggest contract design improvements to mitigate these frictions.

The Impact of Credit on Village Economies.

This paper evaluates the short-term impact of Thailand's 'Million Baht Village Fund'program, among the largest scale government microfinance iniative in the world, using pre- and post-program panel data and quasi-experimental cross-village variation in credit-per-household. We find that the village funds have increased total short-term credit, consumption, agricultural investment, income growth (from business and labor), but decreased overall asset growth. We also find a positive impact on wages, an important general equilibrium effect. The findings are broadly consistent qualitatively with models of credit-constrained household behavior and models of intermediation and growth.

Financial Structure and Economic Welfare: Applied General Equilibrium Development Economics.

This review provides a common framework for researchers thinking about the next generation of micro-founded macro models of growth, inequality, and financial deepening, as well as direction for policy makers targeting microfinance programs to alleviate poverty. Topics include treatment of financial structure general equilibrium models: testing for as-if-complete markets or other financial underpinnings; examining dual-sector models with both a perfectly intermediated sector and a sector in financial autarky, as well as a second generation of these models that embeds information problems and other obstacles to trade; designing surveys to capture measures of income, investment/savings, and flow of funds; and aggregating individuals and households to the level of network, village, or national economy. The review concludes with new directions that overcome conceptual and computational limitations.

Isometric strength assessment, Part II: Static testing does not accurately classify validity of effort.

OBJECTIVE: The purpose of this study was to determine if these two commonly-administered isometric tests are accurate indices of effort. PARTICIPANTS: 34 healthy subjects were tested once giving a maximum voluntary effort and once attempting to feign weakness of 50% of maximum. RESULTS: During feigned weakness sessions, 20 of 34 subjects (58.5%), produced CVs of 15% or less during the Leg Lift. At the 95% CI, the expected frequency of false negatives for feigned weakness is 42.3 to 75.3% for the Leg Lift. At the 95% CI, the expected frequency of false negatives for feigned weakness is 51.9% to 83.3% for the Arm Lift. CONCLUSIONS: Neither isometric lift is appropriate for classifying validity of effort. Use of these isometric lifts should be discontinued for the assessment of effort.

Welfare Gains from Financial Liberalization.

Financial liberalization has been a controversial issue, as empirical evidence for growth enhancing effects is mixed. Here, we find sizable welfare gains from liberalization (cost to repression), though the gain in economic growth is ambiguous. We take the view that financial liberalization is a government policy that alters the path of financial deepening, while financial deepening is endogenously chosen by agents given a policy and occurs in transition towards a distant steady state. This history-dependent view necessitates the use of simulation analysis based on a growth model. Our application is a specific episode: Thailand from 1976 to 1996.

Assessment of belatacept-mediated costimulation blockade through evaluation of CD80/86-receptor saturation.

BACKGROUND: The selective inhibitor of T-cell costimulation, belatacept, blocks CD28-mediated T-cell activation by binding CD80 and CD86 on antigen-presenting cells. Understanding the extent to which belatacept binds to its targets in patients may enable correlation of belatacept exposure to receptor saturation as a pharmacodynamic measure of costimulation blockade. METHODS: Flow cytometry-based receptor competition assays were developed to monitor concentration-dependent occupancy of CD80 and CD86 receptors in whole blood and dendritic cell cultures in vitro. Receptor occupancy was correlated with inhibition of mixed leukocyte reactions and clinical validation was obtained by comparing receptor saturation in whole blood from healthy volunteers and in de novo renal transplant recipients participating in studies comparing cyclosporine and belatacept-based immunosuppression. RESULTS: Belatacept saturated CD80 and CD86 receptors in whole blood and dendritic cell cultures, although the belatacept concentrations required for CD86-receptor saturation were approximately 10-fold higher than those required for CD80 saturation (IC50=0.102 microg/mL vs. 0.009 microg/mL). Primary alloresponses were inhibited at the belatacept concentration required for CD86-receptor saturation, but not at the lower concentration needed to saturate CD80. Whole blood from belatacept-treated patients had significantly lower levels of free CD86 receptors versus pretransplant levels, healthy volunteers, or cyclosporine-treated patients. CD86-receptor saturation correlated with belatacept dose/dose frequency and remained consistently more than 80%. CONCLUSIONS: These results suggest that belatacept-mediated inhibition of alloresponses involved in transplant rejection correlates with CD86 saturation, indicating that CD86-receptor occupancy may be a valid pharmacodynamic measure of costimulation blockade and provide the first direct clinical evidence that belatacept binds to one of its targets.