Endogenous Health Care, Life Expectancy, and Economic Development

We study the endogenous relationship between health care, life expectancy and output in a modified neoclassical growth model. While health care competes resources away from goods production, it prolongs life expectancy which in turn leads to higher capital accumulation. We show that savings and health care are complements in equilibrium, with both rising with economic development. Our model is therefore consistent with several stylized facts, namely, (i) countries spend more on health care as they prosper, (ii) individuals in rich countries tend to live longer, and (iii) population aging is more pronounced in rich countries. Moreover, through simulation, health care and health production technology are found to be growth and welfare enhancing.life expectancy, health care, economic growth, population aging

Corticospinal excitability following short-term motor imagery training of a strength task

Motor imagery and actual movement engage similar neural structures, however, whether they produce similar training-related corticospinal adaptations has yet to be established. The aim of this study was to compare changes in strength and corticospinal excitability following short-term motor imagery strength training and short-term strength training. Transcranial magnetic stimulation (TMS) was applied over the contralateral motor cortex (M1) to elicit motor-evoked potentials in the dominant biceps brachii muscle prior to and following 3-week strength training using actual bicep curls or motor imagery of bicep curls. The strength training (n = 6) and motor imagery (n = 6) groups underwent three supervised training sessions per week for 3 weeks. Participants completed four sets of six to eight repetitions (actual or imagined) at a training load of 80% of their one-repetition maximum. The control group (n = 6) were required to maintain their current level of physical activity. Both training groups exhibited large performance gains in strength (p < 0.001; strength training 39% improvement, imagery 16% improvement), which were significantly different between groups (p = 0.027). TMS revealed that the performance improvements observed in both imagery and strength training were accompanied by increases in corticospinal excitability (p < 0.001), however, these differences were not significantly different between groups (p = 0.920). Our findings suggest that both strength training and motor imagery training utilised similar neural substrates within the primary M1, however, strength training resulted in greater gains in strength than motor imagery strength training. This difference in strength increases may be attributed to adaptations during strength training that are not confined to the primary M1. These findings have theoretical implications for functional equivalent views of motor imagery as well as important therapeutic implications

Overcoming myelosuppression due to synthetic lethal toxicity for FLT3-targeted acute myeloid leukemia therapy.

Activating mutations in FLT3 confer poor prognosis for individuals with acute myeloid leukemia (AML). Clinically active investigational FLT3 inhibitors can achieve complete remissions but their utility has been hampered by acquired resistance and myelosuppression attributed to a 'synthetic lethal toxicity' arising from simultaneous inhibition of FLT3 and KIT. We report a novel chemical strategy for selective FLT3 inhibition while avoiding KIT inhibition with the staurosporine analog, Star 27. Star 27 maintains potency against FLT3 in proliferation assays of FLT3-transformed cells compared with KIT-transformed cells, shows no toxicity towards normal human hematopoiesis at concentrations that inhibit primary FLT3-mutant AML blast growth, and is active against mutations that confer resistance to clinical inhibitors. As a more complete understanding of kinase networks emerges, it may be possible to define anti-targets such as KIT in the case of AML to allow improved kinase inhibitor design of clinical agents with enhanced efficacy and reduced toxicity

Excitation of electronic states in tetrahydrofuran by electron impact

We report on differential and integral cross section measurements for the electron impact excitation of the three lowest lying Rydberg bands of electronic states in tetrahydrofuran. The energy range of the present experiments was 15–50 eV with the angular range of the differential cross section measurements being 15°–90°. The important effects of the long-range target dipole moment and the target dipole polarizability, on the scattering dynamics of this system, are evident from the present results. To the best of our knowledge, there are no other theoretical or experimental data against which we can compare the cross section results from this study

Impact of Hypothyroidism and Heart Failure on Hospitalization Risk.

BackgroundPrior studies suggest that the relationship between hypothyroidism and mortality is dependent on underlying cardiovascular risk. Little is known about the association of hypothyroidism with hospitalization risk, and how these associations are modified by cardiovascular status.MethodsThis study examined the association of thyroid status, defined by serum thyrotropin (TSH), with hospitalization risk among patients who received care at a large university-based tertiary care center between 1990 and 2015. Thyroid status was categorized as hypothyroidism versus euthyroidism (TSH >4.7 vs. 0.3-4.7 mIU/L, respectively). The relationship between thyroid status and hospitalization risk stratified by cardiovascular status was examined using multivariable Cox models.ResultsAmong 52,856 patients who met eligibility criteria, 49,791 (94.2%) had euthyroidism and 3065 (5.8%) had hypothyroidism. In analyses stratified by congestive heart failure (CHF) status, compared to euthyroidism, hypothyroidism was associated with higher risk of hospitalization in those with CHF but slightly lower risk in those without CHF (adjusted hazard ratio [aHRs] = 1.86 [confidence interval (CI) 1.17-2.94] and HR = 0.95 [CI 0.92-0.99], respectively; p = 0.006). In sensitivity analyses accounting for death as a competing event, underlying coronary artery disease modified the hypothyroidism-hospitalization relationship, such that stronger associations were observed among those with versus without coronary artery disease. In competing risk analyses, hypothyroidism was associated with higher versus lower risk of hospitalization among those with versus without cerebrovascular disease, respectively.ConclusionsHypothyroidism is associated with higher hospitalization risk among patients with underlying cardiovascular disease. Future studies are needed to determine whether correction of thyroid status with replacement therapy ameliorates hospitalization risk in this population

Lower bounds on the complexity of simulating quantum gates

We give a simple proof of a formula for the minimal time required to simulate a two-qubit unitary operation using a fixed two-qubit Hamiltonian together with fast local unitaries. We also note that a related lower bound holds for arbitrary n-qubit gates.Comment: 6 page

Assessing alternate sparger configurations to mitigate supply chain risks in single-use bioreactors

Consumable shortages throughout the pandemic introduced unanticipated challenges for continued manufacture of commercial biologics. With single-use systems, the bioreactors themselves are consumables that were impacted by these supply chain shortages. To ensure patient supply of necessary biologics, risk mitigation planning and determining suitable alternatives was required. In this presentation, we detail work performed to allow for continued manufacturing, while facing stock-out risks for single-use bioreactor bags used at both the seed and production stages. Specifically, this work focused on alternate sparger configurations, as the standard configuration used in the production bioreactor stage was unavailable. Additional options for added flexibility at the seed bioreactor stages were evaluated to address stock-out risks, and are discussed. Please click Additional Files below to see the full abstract

Investigating Genetic Determinants of Plasma Inositol Status in Adult Humans

BACKGROUND: Myo-inositol (MI) is incorporated into numerous biomolecules, including phosphoinositides and inositol phosphates. Disturbance of inositol availability or metabolism is associated with various disorders, including neurological conditions and cancers, while supplemental MI has therapeutic potential in conditions such as depression, polycystic ovary syndrome and congenital anomalies. Inositol status may be influenced by diet, synthesis, transport, utilisation and catabolism. OBJECTIVES: We aimed to investigate potential genetic regulation of circulating MI status and to evaluate correlation of MI concentration with other metabolites. METHODS: Gas chromatography mass spectrometry was used to determine plasma MI concentration of more than 2,000 healthy, young adults (aged 18-28 years) from the Trinity Student Study. Genotyping data was used to test association of plasma MI with SNPs in candidate genes, encoding inositol transporters and synthesising enzymes, and test for genome-wide association. We evaluated potential correlation of plasma MI with D-chiro inositol, glucose and other metabolites by Spearman's rank correlation. RESULTS: Mean plasma MI showed a small but significant difference between males and females (28.5 and 26.9 µM, respectively). Candidate gene analysis revealed several nominally significant associations with plasma MI, most notably for SLC5A11, encoding a sodium-coupled inositol transporter, also known as SMIT2 (sodium-dependent myo-inositol transporter 2). However, these did not survive correction for multiple testing. Subsequent testing for genome-wide association with plasma MI did not identify associations of genome-wide significance (p < 5 × 10-8). However, 8 SNPs exceeded the threshold for suggestive significant association with plasma MI concentration (p < 1 × 10-5), 3 of which were located within or close to genes: MTDH, LAPTM4B and ZP2. We found significant positive correlation of plasma MI concentration with concentration of D-chiro-inositol and several other biochemicals including glucose, methionine, betaine, sarcosine and tryptophan. CONCLUSION: Our findings suggest potential for modulation of plasma MI in young adults by variation in SLC5A11 which is worthy of further investigation

Overcoming myelosuppression due to synthetic lethal toxicity for FLT3-targeted acute myeloid leukemia therapy

Activating mutations in FLT3 confer poor prognosis for individuals with acute myeloid leukemia (AML). Clinically active investigational FLT3 inhibitors can achieve complete remissions but their utility has been hampered by acquired resistance and myelosuppression attributed to a 'synthetic lethal toxicity' arising from simultaneous inhibition of FLT3 and KIT. We report a novel chemical strategy for selective FLT3 inhibition while avoiding KIT inhibition with the staurosporine analog, Star 27. Star 27 maintains potency against FLT3 in proliferation assays of FLT3-transformed cells compared with KIT-transformed cells, shows no toxicity towards normal human hematopoiesis at concentrations that inhibit primary FLT3-mutant AML blast growth, and is active against mutations that confer resistance to clinical inhibitors. As a more complete understanding of kinase networks emerges, it may be possible to define anti-targets such as KIT in the case of AML to allow improved kinase inhibitor design of clinical agents with enhanced efficacy and reduced toxicity.published_or_final_versio