Functional Sequential Treatment Allocation

Consider a setting in which a policy maker assigns subjects to treatments, observing each outcome before the next subject arrives. Initially, it is unknown which treatment is best, but the sequential nature of the problem permits learning about the effectiveness of the treatments. While the multi-armed-bandit literature has shed much light on the situation when the policy maker compares the effectiveness of the treatments through their mean, much less is known about other targets. This is restrictive, because a cautious decision maker may prefer to target a robust location measure such as a quantile or a trimmed mean. Furthermore, socio-economic decision making often requires targeting purpose specific characteristics of the outcome distribution, such as its inherent degree of inequality, welfare or poverty. In the present paper we introduce and study sequential learning algorithms when the distributional characteristic of interest is a general functional of the outcome distribution. Minimax expected regret optimality results are obtained within the subclass of explore-then-commit policies, and for the unrestricted class of all policies

Abolishing user fees for children and pregnant women trebled uptake of malaria-related interventions in Kangaba, Mali.

Malaria is the most common cause of morbidity and mortality in children under 5 in Mali. Health centres provide primary care, including malaria treatment, under a system of cost recovery. In 2005, Médecins sans Frontieres (MSF) started supporting health centres in Kangaba with the provision of rapid malaria diagnostic tests and artemisinin-based combination therapy. Initially MSF subsidized malaria tests and drugs to reduce the overall cost for patients. In a second phase, MSF abolished fees for all children under 5 irrespective of their illness and for pregnant women with fever. This second phase was associated with a trebling of both primary health care utilization and malaria treatment coverage for these groups. MSF's experience in Mali suggests that removing user fees for vulnerable groups significantly improves utilization and coverage of essential health services, including for malaria interventions. This effect is far more marked than simply subsidizing or providing malaria drugs and diagnostic tests free of charge. Following the free care strategy, utilization of services increased significantly and under-5 mortality was reduced. Fee removal also allowed for more efficient use of existing resources, reducing average cost per patient treated. These results are particularly relevant for the context of Mali and other countries with ambitious malaria treatment coverage objectives, in accordance with the United Nations Millennium Development Goals. This article questions the effectiveness of the current national policy, and the effectiveness of reducing the cost of drugs only (i.e. partial subsidies) or providing malaria tests and drugs free for under-5s, without abolishing other related fees. National and international budgets, in particular those that target health systems strengthening, could be used to complement existing subsidies and be directed towards effective abolition of user fees. This would contribute to increasing the impact of interventions on population health and, in turn, the effectiveness of aid

Synthetic immunoregulating molecules: A potential bridge between cytostatic chemotherapy and immunotherapy of cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46856/1/262_2004_Article_BF00200075.pd

An insight into polarization states of solid-state organic lasers

The polarization states of lasers are crucial issues both for practical applications and fundamental research. In general, they depend in a combined manner on the properties of the gain material and on the structure of the electromagnetic modes. In this paper, we address this issue in the case of solid-state organic lasers, a technology which enables to vary independently gain and mode properties. Different kinds of resonators are investigated: in-plane micro-resonators with Fabry-Perot, square, pentagon, stadium, disk, and kite shapes, and external vertical resonators. The degree of polarization P is measured in each case. It is shown that although TE modes prevail generally (P>0), kite-shaped micro-laser generates negative values for P, i.e. a flip of the dominant polarization which becomes mostly TM polarized. We at last investigated two degrees of freedom that are available to tailor the polarization of organic lasers, in addition to the pump polarization and the resonator geometry: upon using resonant energy transfer (RET) or upon pumping the laser dye to an higher excited state. We then demonstrate that significantly lower P factors can be obtained.Comment: 12 pages, 12 figure

Master Equation Study of Hydrogen Relaxation Using Complete Sets of State-to-state Transition Rates

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97096/1/AIAA2012-362.pd

The key role of nitric oxide in hypoxia: hypoxic vasodilation and energy supply-demand matching

Significance: a mismatch between energy supply and demand induces tissue hypoxia with the potential to cause cell death and organ failure. Whenever arterial oxygen concentration is reduced, increases in blood flow - 'hypoxic vasodilation' - occur in an attempt to restore oxygen supply. Nitric oxide is a major signalling and effector molecule mediating the body's response to hypoxia, given its unique characteristics of vasodilation (improving blood flow and oxygen supply) and modulation of energetic metabolism (reducing oxygen consumption and promoting utilization of alternative pathways). Recent advances: this review covers the role of oxygen in metabolism and responses to hypoxia, the hemodynamic and metabolic effects of nitric oxide, and mechanisms underlying the involvement of nitric oxide in hypoxic vasodilation. Recent insights into nitric oxide metabolism will be discussed, including the role for dietary intake of nitrate, endogenous nitrite reductases, and release of nitric oxide from storage pools. The processes through which nitric oxide levels are elevated during hypoxia are presented, namely (i) increased synthesis from nitric oxide synthases, increased reduction of nitrite to nitric oxide by heme- or pterin-based enzymes and increased release from nitric oxide stores, and (ii) reduced deactivation by mitochondrial cytochrome c oxidase. Critical issues: several reviews covered modulation of energetic metabolism by nitric oxide, while here we highlight the crucial role NO plays in achieving cardiocirculatory homeostasis during acute hypoxia through both vasodilation and metabolic suppression Future directions: we identify a key position for nitric oxide in the body's adaptation to an acute energy supply-demand mismatc

Multi-phase characterization of AGN winds in 5 local type-2 quasars

We present MEGARA (Multi-Espectr\'ografo en GTC de Alta Resoluci\'on para Astronom\'ia) Integral Field Unit (IFU) observations of 5 local type-2 quasars (QSO2s, z $\sim 0.1$) from the Quasar Feedback (QSOFEED) sample. These active galactic nuclei (AGN) have bolometric luminosities of 10$^{45.5-46}$ erg/s and stellar masses of $\sim$10$^{11}$ M$_{\odot}$. We explore the kinematics of the ionized gas through the [O~III]$\lambda$5007 $\r{A}$ emission line. The nuclear spectra of the 5 QSO2s, extracted in a circular aperture of $\sim$ 1.2" ($\sim$ 2.2 kpc) in diameter, show signatures of high velocity winds in the form of broad (full width at half maximum; 1300$\leq$FWHM$\leq$2240 km/s and blueshifted components. We find that 4 out of the 5 QSO2s present outflows that we can resolve with our seeing-limited data, and they have radii ranging from 3.1 to 12.6 kpc. In the case of the two QSO2s with extended radio emission, we find that it is well-aligned with the outflows, suggesting that low-power jets might be compressing and accelerating the ionized gas in these radio-quiet QSO2s. In the four QSO2s with spatially resolved outflows, we measure ionized mass outflow rates of 3.3-6.5 Msun/yr when we use [S~II]-based densities, and of 0.7-1.6 Msun/yr when trans-auroral line-based densities are considered instead. We compare them with the corresponding molecular mass outflow rates (8 - 16 Msun/yr), derived from CO(2-1) ALMA observations at 0.2" resolution. Both phases show lower outflow mass rates than those expected from observational scaling relations where uniform assumptions on the outflow properties were adopted. This might be indicating that the AGN luminosity is not the only driver of massive outflows and/or that these relations need to be re-scaled using accurate outflow properties. We do not find a significant impact of the outflows on the global star formation rates.Comment: 24 pages, 13 figures and 4 tables. Accepted for publication in A&A; A&A 665, A55 (2023); doi: 10.1051/0004-6361/20234771

ALMA captures feeding and feedback from the active galactic nucleus in NGC 613

We report ALMA observations of CO(3-2) emission in the Seyfert/nuclear starburst galaxy NGC 613, at a spatial resolution of 17 pc, as part of our NUclei of GAlaxies (NUGA) sample. Our aim is to investigate the morphology and dynamics of the gas inside the central kiloparsec, and to probe nuclear fueling and feedback phenomena. The morphology of CO(3-2) line emission reveals a two-arm trailing nuclear spiral at r≤ 100 pc and a circumnuclear ring at a radius of ∼350 pc that is coincident with the star-forming ring seen in the optical images. Also, we find evidence for a filamentary structure connecting the ring and the nuclear spiral. The ring reveals two breaks into two winding spiral arms corresponding to the dust lanes in the optical images. The molecular gas in the galaxy disk is in a remarkably regular rotation, however the kinematics in the nuclear region are very skewed. The nuclear spectrum of CO and dense gas tracers HCN(4-3), HCO+(4-3), and CS(7-6) show broad wings up to \ub1300 km s-1, associated with a molecular outflow emanating from the nucleus (r ∼ 25 pc). We derive a molecular outflow mass Mout=2 7 106 M⊙ and a mass outflow rate of M out = 27 M⊙ yr-1. The molecular outflow energetics exceed the values predicted by AGN feedback models: the kinetic power of the outflow corresponds to PK, out=20%LAGN and the momentum rate is M outv ∼400LAGN/c. The outflow is mainly boosted by the AGN through entrainment by the radio jet, but given the weak nuclear activity of NGC 613, we might be witnessing a fossil outflow resulting from a previously strong AGN that has now faded. Furthermore, the nuclear trailing spiral observed in CO emission is inside the inner Lindblad resonance ring of the bar. We compute the gravitational torques exerted in the gas to estimate the efficiency of the angular momentum exchange. The gravity torques are negative from 25 to 100 pc and the gas loses its angular momentum in a rotation period, providing evidence for a highly efficient inflow towards the center. This phenomenon shows that the massive central black hole has significant dynamical influence on the gas, triggering the inflowing of molecular gas to feed the black hole

An expression signature of the angiogenic response in gastrointestinal neuroendocrine tumours: correlation with tumour phenotype and survival outcomes.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are heterogeneous with respect to biological behaviour and prognosis. As angiogenesis is a renowned pathogenic hallmark as well as a therapeutic target, we aimed to investigate the prognostic and clinico-pathological role of tissue markers of hypoxia and angiogenesis in GEP-NETs. METHODS: Tissue microarray (TMA) blocks were constructed with 86 tumours diagnosed from 1988 to 2010. Tissue microarray sections were immunostained for hypoxia inducible factor 1α (Hif-1α), vascular endothelial growth factor-A (VEGF-A), carbonic anhydrase IX (Ca-IX) and somatostatin receptors (SSTR) 1–5, Ki-67 and CD31. Biomarker expression was correlated with clinico-pathological variables and tested for survival prediction using Kaplan–Meier and Cox regression methods. RESULTS: Eighty-six consecutive cases were included: 51% male, median age 51 (range 16–82), 68% presenting with a pancreatic primary, 95% well differentiated, 51% metastatic. Higher grading (P=0.03), advanced stage (P<0.001), high Hif-1α and low SSTR-2 expression (P=0.03) predicted for shorter overall survival (OS) on univariate analyses. Stage, SSTR-2 and Hif-1α expression were confirmed as multivariate predictors of OS. Median OS for patients with SSTR-2+/Hif-1α-tumours was not reached after median follow up of 8.8 years, whereas SSTR-2-/Hif-1α+ GEP-NETs had a median survival of only 4.2 years (P=0.006). CONCLUSION: We have identified a coherent expression signature by immunohistochemistry that can be used for patient stratification and to optimise treatment decisions in GEP-NETs independently from stage and grading. Tumours with preserved SSTR-2 and low Hif-1α expression have an indolent phenotype and may be offered less aggressive management and less stringent follow up