The midbrain to pons ratio: a simple and specific MRI sign of progressive supranuclear palsy.

MRI-based measurements used to diagnose progressive supranuclear palsy (PSP) typically lack pathologic verification and are not easy to use routinely. We aimed to develop in histologically proven disease a simple measure of the midbrain and pons on sagittal MRI to identify PSP

Mucosal Macrophages in Intestinal Homeostasis and Inflammation

Intestinal macrophages are essential for local homeostasis and in keeping a balance between commensal microbiota and the host. However, they also play essential roles in inflammation and protective immunity, when they change from peaceful regulators to powerful aggressors. As a result, activated macrophages are important targets for treatment of inflammatory bowel diseases such as Crohn's disease. Until recently, the complexity and heterogeneity of intestinal macrophages have been underestimated and here we review current evidence that there are distinct populations of resident and inflammatory macrophages in the intestine. We describe the mechanisms that ensure macrophages remain partially inert in the healthy gut and cannot promote inflammation despite constant exposure to bacteria and other stimuli. This may be because the local environment ‘conditions’ macrophage precursors to become unresponsive after they arrive in the gut. Nevertheless, this permits some active, physiological functions to persist. A new population of pro-inflammatory macrophages appears in inflammation and we review the evidence that this involves recruitment of a distinct population of fully responsive monocytes, rather than alterations in the existing cells. A constant balance between these resident and inflammatory macrophages is critical for maintaining the status quo in healthy gut and ensuring protective immunity when required

LR characterization of chirotopes of finite planar families of pairwise disjoint convex bodies

We extend the classical LR characterization of chirotopes of finite planar families of points to chirotopes of finite planar families of pairwise disjoint convex bodies: a map \c{hi} on the set of 3-subsets of a finite set I is a chirotope of finite planar families of pairwise disjoint convex bodies if and only if for every 3-, 4-, and 5-subset J of I the restriction of \c{hi} to the set of 3-subsets of J is a chirotope of finite planar families of pairwise disjoint convex bodies. Our main tool is the polarity map, i.e., the map that assigns to a convex body the set of lines missing its interior, from which we derive the key notion of arrangements of double pseudolines, introduced for the first time in this paper.Comment: 100 pages, 73 figures; accepted manuscript versio

The genetic profile of elite youth soccer players and its association with power and speed depends on maturity status

We investigated the association of multiple single nucleotide polymorphisms (SNPs) with athlete status and power/speed performance in elite male youth soccer players (ESP) and control participants (CON) at different stages of maturity. ESP (n = 535; aged 8–23 years) and CON (n = 151; aged 9–26 years) were genotyped for 10 SNPs and grouped according to years from predicted peak-height-velocity (PHV), i.e. pre- or post-PHV, to determine maturity status. Participants performed bilateral vertical countermovement jumps, bilateral horizontal-forward countermovement jumps, 20m sprints and modified 505-agility tests. Compared to CON, pre-PHV ESP demonstrated a higher ACTN3 (rs1815739) XX (‘endurance’) genotype frequency distribution, while post-PHV ESP revealed a higher frequency distribution of the PPARA (rs4253778) C-allele, AGT (rs699) GG genotype and NOS3 (rs2070744) T-allele (‘power’ genotypes/alleles). BDNF (rs6265) CC, COL5A1 (rs12722) CC and NOS3 TT homozygotes sprinted quicker than A-allele carriers, CT heterozygotes and CC homozygotes, respectively. COL2A1 (rs2070739) CC and AMPD1 (rs17602729) GG homozygotes sprinted faster than their respective minor allele carrier counterparts in CON and pre-PHV ESP, respectively. BDNF CC homozygotes jumped further than T-allele carriers, while ESP COL5A1 CC homozygotes jumped higher than TT homozygotes. To conclude, we have shown for the first time that pre- and post-PHV ESP have distinct genetic profiles, with pre-PHV ESP more suited for endurance, and post-PHV ESP for power and speed (the latter phenotypes being crucial attributes for post-PHV ESP). We have also demonstrated that power, acceleration and sprint performance were associated with five SNPs, both individually and in combination, possibly by influencing muscle size and neuromuscular activation

Global Burden of Sickle Cell Anaemia in Children under Five, 2010-2050: Modelling Based on Demographics, Excess Mortality, and Interventions

The global burden of sickle cell anaemia (SCA) is set to rise as a consequence of improved survival in high-prevalence low- and middle-income countries and population migration to higher-income countries. The host of quantitative evidence documenting these changes has not been assembled at the global level. The purpose of this study is to estimate trends in the future number of newborns with SCA and the number of lives that could be saved in under-five children with SCA by the implementation of different levels of health interventions.First, we calculated projected numbers of newborns with SCA for each 5-y interval between 2010 and 2050 by combining estimates of national SCA frequencies with projected demographic data. We then accounted for under-five mortality (U5m) projections and tested different levels of excess mortality for children with SCA, reflecting the benefits of implementing specific health interventions for under-five patients in 2015, to assess the number of lives that could be saved with appropriate health care services. The estimated number of newborns with SCA globally will increase from 305,800 (confidence interval [CI]: 238,400-398,800) in 2010 to 404,200 (CI: 242,500-657,600) in 2050. It is likely that Nigeria (2010: 91,000 newborns with SCA [CI: 77,900-106,100]; 2050: 140,800 [CI: 95,500-200,600]) and the Democratic Republic of the Congo (2010: 39,700 [CI: 32,600-48,800]; 2050: 44,700 [CI: 27,100-70,500]) will remain the countries most in need of policies for the prevention and management of SCA. We predict a decrease in the annual number of newborns with SCA in India (2010: 44,400 [CI: 33,700-59,100]; 2050: 33,900 [CI: 15,900-64,700]). The implementation of basic health interventions (e.g., prenatal diagnosis, penicillin prophylaxis, and vaccination) for SCA in 2015, leading to significant reductions in excess mortality among under-five children with SCA, could, by 2050, prolong the lives of 5,302,900 [CI: 3,174,800-6,699,100] newborns with SCA. Similarly, large-scale universal screening could save the lives of up to 9,806,000 (CI: 6,745,800-14,232,700) newborns with SCA globally, 85% (CI: 81%-88%) of whom will be born in sub-Saharan Africa. The study findings are limited by the uncertainty in the estimates and the assumptions around mortality reductions associated with interventions.Our quantitative approach confirms that the global burden of SCA is increasing, and highlights the need to develop specific national policies for appropriate public health planning, particularly in low- and middle-income countries. Further empirical collaborative epidemiological studies are vital to assess current and future health care needs, especially in Nigeria, the Democratic Republic of the Congo, and India

The role of salt abuse on risk for hypercalciuria

<p>Abstract</p> <p>Background</p> <p>Elevated sodium excretion in urine resulting from excessive sodium intake can lead to hypercalciuria and contribute to the formation of urinary stones. The aim of this study was to evaluate salt intake in patients with urinary lithiasis and idiopathic hypercalciuria (IH).</p> <p>Methods</p> <p>Between August 2007 and June 2008, 105 lithiasic patients were distributed into 2 groups: Group 1 (n = 55): patients with IH (urinary calcium excretion > 250 mg in women and 300 mg in men with normal serum calcium); Group 2 (n = 50): normocalciuric patients (NC). Inclusion criteria were: age over 18 years, normal renal function (creatinine clearance ≥ 60 ml/min), absent proteinuria and negative urinary culture. Pregnant women, patients with intestinal pathologies, chronic diarrhea or using corticoids were excluded. The protocol of metabolic investigation was based on non-consecutive collection of two 24-hour samples for dosages of: calcium, sodium, uric acid, citrate, oxalate, magnesium and urinary volume. Food intake was evaluated by the three-day dietary record quantitative method, and the Body Mass Index (BMI) was calculated and classified according to the World Health Organization (WHO). Sodium intake was evaluated based on 24-hour urinary sodium excretion.</p> <p>Results</p> <p>The distribution in both groups as regards mean age (42.11 ± 10.61 vs. 46.14 ± 11.52), weight (77.14 ± 16.03 vs. 75.99 ± 15.80), height (1.64 ± 0.10 vs. 1.64 <b>± plusorminus </b>0.08) and BMI (28.78 ± 5.81 vs. 28.07 ± 5.27) was homogeneous. Urinary excretion of calcium (433.33 ± 141.92 vs. 188.93 ± 53.09), sodium (280.08 ± 100.94 vs. 200.44.93 ± 65.81), uric acid (880.63 ± 281.50 vs. 646.74 ± 182.76) and magnesium (88.78 ± 37.53 vs. 64.34 ± 31.84) was significantly higher in the IH group (p < 0.05). There was no statistical difference in calcium intake between the groups, and there was significantly higher salt intake in patients with IH than in NC.</p> <p>Conclusions</p> <p>This study showed that salt intake was higher in patients with IH as compared to NC.</p

Eta Carinae and the Luminous Blue Variables

We evaluate the place of Eta Carinae amongst the class of luminous blue variables (LBVs) and show that the LBV phenomenon is not restricted to extremely luminous objects like Eta Car, but extends luminosities as low as log(L/Lsun) = 5.4 - corresponding to initial masses ~25 Msun, and final masses as low as ~10-15 Msun. We present a census of S Doradus variability, and discuss basic LBV properties, their mass-loss behaviour, and whether at maximum light they form pseudo-photospheres. We argue that those objects that exhibit giant Eta Car-type eruptions are most likely related to the more common type of S Doradus variability. Alternative atmospheric models as well as sub-photospheric models for the instability are presented, but the true nature of the LBV phenomenon remains as yet elusive. We end with a discussion on the evolutionary status of LBVs - highlighting recent indications that some LBVs may be in a direct pre-supernova state, in contradiction to the standard paradigm for massive star evolution.Comment: 27 pages, 6 figures, Review Chapter in "Eta Carinae and the supernova imposters" (eds R. Humphreys and K. Davidson) new version submitted to Springe

Autophagy fights disease through cellular self-digestion

Autophagy, or cellular self-digestion, is a cellular pathway involved in protein and organelle degradation, with an astonishing number of connections to human disease and physiology. For example, autophagic dysfunction is associated with cancer, neurodegeneration, microbial infection and ageing. Paradoxically, although autophagy is primarily a protective process for the cell, it can also play a role in cell death. Understanding autophagy may ultimately allow scientists and clinicians to harness this process for the purpose of improving human health.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62766/1/nature06639.pd

The stellar and sub-stellar IMF of simple and composite populations

The current knowledge on the stellar IMF is documented. It appears to become top-heavy when the star-formation rate density surpasses about 0.1Msun/(yr pc^3) on a pc scale and it may become increasingly bottom-heavy with increasing metallicity and in increasingly massive early-type galaxies. It declines quite steeply below about 0.07Msun with brown dwarfs (BDs) and very low mass stars having their own IMF. The most massive star of mass mmax formed in an embedded cluster with stellar mass Mecl correlates strongly with Mecl being a result of gravitation-driven but resource-limited growth and fragmentation induced starvation. There is no convincing evidence whatsoever that massive stars do form in isolation. Various methods of discretising a stellar population are introduced: optimal sampling leads to a mass distribution that perfectly represents the exact form of the desired IMF and the mmax-to-Mecl relation, while random sampling results in statistical variations of the shape of the IMF. The observed mmax-to-Mecl correlation and the small spread of IMF power-law indices together suggest that optimally sampling the IMF may be the more realistic description of star formation than random sampling from a universal IMF with a constant upper mass limit. Composite populations on galaxy scales, which are formed from many pc scale star formation events, need to be described by the integrated galactic IMF. This IGIMF varies systematically from top-light to top-heavy in dependence of galaxy type and star formation rate, with dramatic implications for theories of galaxy formation and evolution.Comment: 167 pages, 37 figures, 3 tables, published in Stellar Systems and Galactic Structure, Vol.5, Springer. This revised version is consistent with the published version and includes additional references and minor additions to the text as well as a recomputed Table 1. ISBN 978-90-481-8817-