Federal Transfers and the Tax efforts of the States in India

The paper has examined the the impact of federal fiscal transfers on the budget of the state (sub-central) governments in India. The relationship between the federal fiscal transfers and the tax efforts of the 14 major Indian states have been anlysed for fifteen years (from 1970-71 to 1984-85)through a panel dadat set. Fixed efeect model and its variants have been employed. The study found that the federal transfers have dampaned the tax efforts of states in India. Hence, a hiher weightaege for the 'tax effort criterion' has been suggested in the vertical devolution formula of the Indian Finance Commission to ensure efficiency.Federal Transfers; Tax Efforts; Fiscal Federalism in India; Efficiency; Vertical fiscal balance

Federal Transfers and the Tax efforts of the States in India

The paper has examined the the impact of federal fiscal transfers on the budget of the state (sub-central) governments in India. The relationship between the federal fiscal transfers and the tax efforts of the 14 major Indian states have been anlysed for fifteen years (from 1970-71 to 1984-85)through a panel dadat set. Fixed efeect model and its variants have been employed. The study found that the federal transfers have dampaned the tax efforts of states in India. Hence, a hiher weightaege for the 'tax effort criterion' has been suggested in the vertical devolution formula of the Indian Finance Commission to ensure efficiency

Evaluating Calculated Free Testosterone as a Predictor of Morbidity and Mortality Independent of Testosterone for Cross-sectional and 5-Year Longitudinal Health Outcomes in Older Men: The Concord Health and Ageing in Men Project

To determine whether calculated free testosterone (cFT) provides prognostic information independent of serum T for predicting morbidity and mortality in older men in cross-sectional and 5-year longitudinal analyses. We studied men aged ≥70 years at baseline (n = 1,705), 2-year and 5-year measuring serum T (liquid chromatography-mass spectrometry), SHBG (immunoassay), cFT (an assumption-free empirical formula) together with 24 morbidity and 4 mortality outcomes. For cross-sectional and longitudinal analyses we employed a joint prediction model using generalized estimating equation models adjusted for age, smoking, comorbidities, and body mass index (BMI) with men having both normal T and normal cFT as referent group. Most morbidity and mortality outcomes were predicted by a combination of low T and cFT (LL). By contrast, only a single morbidity outcome in cross-sectional and none in longitudinal analysis was predicted by low T/normal cFT (LN) or normal T/low cFT (NL) without significant LL associations (isolated discordance). While for the few outcomes that predicted morbidity in men with discordances (LN or NL), these predictions only occurred when LL was also significant. Hence, for morbidity or mortality prediction in older men, discordance between cFT and T is unusual and isolated discordance is rare, so that cFT provides minimal independent prognostic information over serum T.NHMRC, Sydney Medical School Foundation, and Ageing and Alzheimer’s Institute

Does combined osteopenia/osteoporosis and sarcopenia confer greater risk of falls and fracture than either condition alone in older men? The Concord Health and Ageing in Men Project

Background It is unclear whether older men with osteopenia/osteoporosis and sarcopenia (so-called osteosarcopenia) are at greater risk of falls and fractures than those with either condition alone. Methods One thousand five hundred seventy-five community-dwelling men aged ≥70 years had appendicular lean mass, total hip and lumbar spine bone mineral density determined by dual-energy x-ray absorptiometry, and completed hand grip strength and gait speed tests. Osteopenia/osteoporosis was defined as a T-score at any site ≤−1.0 SD. Sarcopenia was defined using the European Working Group on Sarcopenia algorithm. Participants were contacted every 4 months for 6 ± 2 years to ascertain incident fractures (confirmed by radiographic reports) and for 2 years for incident falls. Results Prevalence of osteosarcopenia was 8%, while 34% of participants had osteopenia/osteoporosis alone and 7% had sarcopenia alone. Men with osteosarcopenia had significantly increased fall (incidence rate ratio: 1.41; 95% confidence interval [CI]: 1.02 to 1.95) and fracture risk (hazard ratio: 1.87; 95% CI: 1.07 to 3.26) compared with men with neither osteopenia/osteoporosis nor sarcopenia. There was no statistical interaction between osteopenia/osteoporosis and sarcopenia, and falls and fracture risk were not different for osteosarcopenia compared with either condition alone (all p > .05). Conclusions Community-dwelling older men with combined osteopenia/osteoporosis and sarcopenia do not have increased falls and fracture risk compared with those with either condition. Further research is required to clarify whether the term “osteosarcopenia” has any meaning above and beyond either term alone and therefore potential clinical utility for falls and fracture prediction.NHMRC (project grant number 301916) and the Ageing and Alzheimer’s Institute. D.Scott is supported by a NHRMC Career Development Fellowship (GNT1123014

Community-dwelling men with dementia are at high risk of hip but not any other fracture: The Concord Health and Ageing in Men Project

Aim The aim of the present longitudinal study of community‐dwelling older men was to examine the association between cognitive status at baseline, and falls, fractures and bone loss over time. Methods In the Concord Health and Aging in Men Project, 1705 community‐dwelling men aged 70–97 years had detailed baseline clinical assessment of cognitive status (dementia, mild cognitive impairment [MCI] and normal cognition), as well as depression, physical activity, neuromuscular function, health status, sociodemographics, comorbidities, medication use and serum 25 hydroxyvitamin D, 1,25 dihydroxyvitamin D and parathyroid hormone levels. During a mean follow‐up period of 6 years, participants were contacted 4‐monthly to ascertain incident falls and fractures, the latter being confirmed by radiographic reports. Bone mineral density was measured by dual X‐ray absorptiometry at multiple time‐points. Results At baseline, 120 men were assessed to have MCI and 93 men to have dementia. Over time, there were 162 first incident fractures, including 43 hip and 32 vertebral fractures. In univariate models, baseline dementia, but not MCI, predicted an increased incidence of hip fracture (HR 6.95, 95% CI 3.47–13.96), but not vertebral (HR 2.26, 95% CI 0.79–6.46) or non‐hip non‐vertebral fracture (HR 0.73, 95% CI 0.27–1.99). The strong risk of hip fractures associated with dementia remained after accounting for potential confounders (HR 4.44, 95% CI 1.97–9.98). In multivariate analyses, dementia (incidence rate ratio 2.26, 95% CI 1.70–2.99), but not MCI, was associated with an increased risk of falls compared with normal cognition. There was no association between baseline dementia and change in bone mineral density. Conclusions Older men with dementia, but not MCI, have a greater tendency to fall and sustain hip fractures, but not any other types of fractures.NHMRC, Ageing and Alzheimer's Institute, Sydney Medical School Foundatio

Association between pain and the frailty phenotype in older men: longitudinal results from the Concord Health and Ageing in Men Project (CHAMP)

Objectives to determine whether pain increases the risk of developing the frailty phenotype and whether frailty increases the risk of developing chronic or intrusive pain, using longitudinal data. Design/Setting longitudinal data from the Concord Health and Ageing in Men Project (CHAMP), a prospective population based cohort study. Participants a total of 1,705 men aged 70 years or older, living in an urban area of New South Wales, Australia. Measurements data on the presence of chronic pain (daily pain for at least 3 months), intrusive pain (pain causing moderate to severe interference with activities) and the criteria for the Cardiovascular Health Study (CHS) frailty phenotype were collected in three waves, from January 2005 to October 2013. Data on age, living arrangements, education, smoking status, alcohol consumption, body mass index, comorbidities, cognitive function, depressive symptoms and history of vertebral or hip fracture were also collected and included as covariates in the analyses. Results a total of 1,705 participants were included at baseline, of whom 1,332 provided data at the 2-year follow-up and 940 at the 5-year follow-up. Non-frail (robust and pre-frail) men who reported chronic pain were 1.60 (95% confidence interval (CI): 1.02–2.51, P = 0.039) times more likely to develop frailty at follow-up, compared to those with no pain. Intrusive pain did not significantly increase the risk of future frailty. Likewise, the frailty status was not associated with future chronic or intrusive pain in the adjusted analysis. Conclusions the presence of chronic pain increases the risk of developing the frailty phenotype in community-dwelling older men.NHMRC, The Ageing and Alzheimer's Institut

Too Much Medicine in older people? Deprescribing through Shared Decision Making

Too much medicine is an increasingly recognised problem,1 2 and one manifestation is inappropriate polypharmacy in older people. Polypharmacy is usually defined as taking more than five regular prescribed medicines.3 It can be appropriate (when potential benefits outweigh potential harms)4 but increases the risk of older people experiencing adverse drug reactions, impaired physical and cognitive function, and hospital admission.5 6 7 There is limited evidence to inform polypharmacy in older people, especially those with multimorbidity, cognitive impairment, or frailty.8 Systematic reviews of medication withdrawal trials (deprescribing) show that reducing specific classes of medicines may decrease adverse events and improve quality of life.9 10 11 Two recent reviews of the literature on deprescribing stressed the importance of patient involvement and shared decision making.12 13 Patients and clinicians typically overestimate the benefits of treatments and underestimate their harms.14 When they engage in shared decision making they become better informed about potential outcomes and as a result patients tend to choose more conservative options (eg, fewer medicines), facilitating deprescribing.15 However, shared decision making in this context is not easy, and there is little guidance on how to do it.16 We draw together evidence from the psychology, communication, and decision making literature (see appendix on thebmj.com). For each step of the shared decision making process we describe the unique tasks required for deprescribing decisions; identify challenges for older adults, their companions, and clinicians (figure); give practical advice on how challenges may be overcome; highlight where more work is needed; and identify priorities for future research (table). Key messages Deprescribing is a process of planned and supervised tapering or ceasing of inappropriate medicines Shared decision making should be an integral part of the deprescribing process Many factors affect this process, including trust in clinicians’ advice, contradictory patient attitudes about medication, cognitive biases that lead to a preference for the status quo and positive information, and information processing difficulties There is uncertainty about the effect of risk communication and preference elicitation tools in older people Older people’s preferences for discussing life expectancy and quality of life vary widely, but even those who wish to delegate their decisions still appreciate discussion of optionsJJ is supported by a National Health and Medical Research Council (NHMRC) early career fellowship (1037028) and KM is supported by an NHMRC career development fellowship (1029241

Structural basis of the pleiotropic and specific phenotypic consequences of missense mutations in the multifunctional NAD(P)H:quinone oxidoreductase 1 and their pharmacological rescue

The multifunctional nature of human flavoproteins is critically linked to their ability to populate multiple conformational states. Ligand binding, post-translational modifications and disease-associated mutations can reshape this functional landscape, although the structure-function relationships of these effects are not well understood. Herein, we characterized the structural and functional consequences of two mutations (the cancer-associated P187S and the phosphomimetic S82D) on different ligation states which are relevant to flavin binding, intracellular stability and catalysis of the disease-associated NQO1 flavoprotein. We found that these mutations affected the stability locally and their effects propagated differently through the protein structure depending both on the nature of the mutation and the ligand bound, showing directional preference from the mutated site and leading to specific phenotypic manifestations in different functional traits (FAD binding, catalysis and inhibition, intracellular stability and pharmacological response to ligands). Our study thus supports that pleitropic effects of disease-causing mutations and phosphorylation events on human flavoproteins may be caused by long-range structural propagation of stability effects to different functional sites that depend on the ligation-state and site-specific perturbations. Our approach can be of general application to investigate these pleiotropic effects at the flavoproteome scale in the absence of high-resolution structural models. © 202

The Ultimate Fate of Supercooled Liquids

In recent years it has become widely accepted that a dynamical length scale {\xi}_{\alpha} plays an important role in supercooled liquids near the glass transition. We examine the implications of the interplay between the growing {\xi}_{\alpha} and the size of the crystal nucleus, {\xi}_M, which shrinks on cooling. We argue that at low temperatures where {\xi}_{\alpha} > {\xi}_M a new crystallization mechanism emerges enabling rapid development of a large scale web of sparsely connected crystallinity. Though we predict this web percolates the system at too low a temperature to be easily seen in the laboratory, there are noticeable residual effects near the glass transition that can account for several previously observed unexplained phenomena of deeply supercooled liquids including Fischer clusters, and anomalous crystal growth near T_g