Socioeconomic Inequalities in Mortality Rates in Old Age in the World Health Organization Europe Region

Socioeconomic adversity is among the foremost fundamental causes of human suffering, and this is no less true in old age. Recent reports on socioeconomic inequalities in mortality rate in old age suggest that a low socioeconomic position continues to increase the risk of death even among the oldest old. We aimed to examine the evidence for socioeconomic mortality rate inequalities in old age, including information about associations with various indicators of socioeconomic position and for various geographic locations within the World Health Organization Region for Europe. The articles included in this review leave no doubt that inequalities in mortality rate by socioeconomic position persist into the oldest ages for both men and women in all countries for which information is available, although the relative risk measures observed were rarely higher than 2.00. Still, the available evidence base is heavily biased geographically, inasmuch as it is based largely on national studies from Nordic and Western European countries and local studies from urban areas in Southern Europe. This bias will hamper the design of European-wide policies to reduce inequalities in mortality rate. We call for a continuous update of the empiric evidence on socioeconomic inequalities in mortality rate

Patchiness and Demographic Noise in Three Ecological Examples

Understanding the causes and effects of spatial aggregation is one of the most fundamental problems in ecology. Aggregation is an emergent phenomenon arising from the interactions between the individuals of the population, able to sense only -at most- local densities of their cohorts. Thus, taking into account the individual-level interactions and fluctuations is essential to reach a correct description of the population. Classic deterministic equations are suitable to describe some aspects of the population, but leave out features related to the stochasticity inherent to the discreteness of the individuals. Stochastic equations for the population do account for these fluctuation-generated effects by means of demographic noise terms but, owing to their complexity, they can be difficult (or, at times, impossible) to deal with. Even when they can be written in a simple form, they are still difficult to numerically integrate due to the presence of the "square-root" intrinsic noise. In this paper, we discuss a simple way to add the effect of demographic stochasticity to three classic, deterministic ecological examples where aggregation plays an important role. We study the resulting equations using a recently-introduced integration scheme especially devised to integrate numerically stochastic equations with demographic noise. Aimed at scrutinizing the ability of these stochastic examples to show aggregation, we find that the three systems not only show patchy configurations, but also undergo a phase transition belonging to the directed percolation universality class.Comment: 20 pages, 5 figures. To appear in J. Stat. Phy

Patterns, Predictors, and Outcomes of Falls Trajectories in Older Adults: The MOBILIZE Boston Study with 5 Years of Follow-Up

Background: Falls may occur as unpredictable events or in patterns indicative of potentially modifiable risks and predictive of adverse outcomes. Knowing the patterns, risks, and outcomes of falls trajectories may help clinicians plan appropriate preventive measures. We hypothesized that clinically distinct trajectories of falls progression, baseline predictors and their coincident clinical outcomes could be identified. Methods: We studied 765 community-dwelling participants in the MOBILIZE Boston Study, who were aged 70 and older and followed prospectively for falls over 5 years. Baseline demographic and clinical data were collected by questionnaire and a comprehensive clinic examination. Falls, injuries, and hospitalizations were recorded prospectively on daily calendars. Group-Based Trajectory Modeling (GBTM) was used to identify trajectories. Results: We identified 4 distinct trajectories: No Falls (30.1%), Cluster Falls (46.1%), Increasing Falls (5.8%) and Chronic Recurring Falls (18.0%). Predictors of Cluster Falls were faster gait speed (OR 1.69 (95CI, 1.50–2.56)) and fall in the past year (OR 3.52 (95CI, 2.16–6.34)). Predictors of Increasing Falls were Diabetes Mellitus (OR 4.3 (95CI, 1.4–13.3)) and Cognitive Impairment (OR 2.82 (95CI, 1.34–5.82)). Predictors of Chronic Recurring Falls were multi-morbidity (OR 2.24 (95CI, 1.60–3.16)) and fall in the past year (OR 3.82 (95CI, 2.34–6.23)). Symptoms of depression were predictive of all falls trajectories. In the Chronic Recurring Falls trajectory group the incidence rate of Hospital visits was 121 (95% CI 63–169) per 1,000 person-years; Injurious falls 172 (95% CI 111–237) per 1,000 person-years and Fractures 41 (95% CI 9–78) per 1,000 person-years. Conclusions: Falls may occur in clusters over discrete intervals in time, or as chronically increasing or recurring events that have a relatively greater risk of adverse outcomes. Patients with multiple falls, multimorbidity, and depressive symptoms should be targeted for preventive measures

Vibrational Spectra of a Mechanosensitive Channel

We report the simulated vibrational spectra of a mechanosensitive membrane channel in different gating states. Our results show that while linear absorption is insensitive to structural differences, linear dichroism and sum-frequency generation spectroscopies are sensitive to the orientation of the transmembrane helices, which is changing during the opening process. Linear dichroism cannot distinguish an intermediate structure from the closed structure, but sum-frequency generation can. In addition, we find that two-dimensional infrared spectroscopy can be used to distinguish all three investigated gating states of the mechanosensitive membrane channel.

If it looks like a duck: Fish fit the criteria for pain perception

Whereas we have denied the experience of pain to animals, including human babies, the evidence is becoming clearer that animals across a variety of species have the capacity to feel pain (Bellieni, 2012). As converging findings are collected from pain studies and the study of cognition, it is becoming harder to deny that fish are among the species that do feel pain

If it looks like a duck: Fish fit the criteria for pain perception

Whereas we have denied the experience of pain to animals, including human babies, the evidence is becoming clearer that animals across a variety of species have the capacity to feel pain (Bellieni, 2012). As converging findings are collected from pain studies and the study of cognition, it is becoming harder to deny that fish are among the species that do feel pain

TNF and PGE2 in human monocyte-derived macrophages infected with Chlamydia trachomatis

In this study levels of prostaglandin E2 (PGE2), tumour necrosis factor (TNF) and interleukin-1 (IL-1) alpha in medium from monocyte derived macrophages (MdM) infected with Chlamydia trachomatis (L2/434/Bu or K biovars). TNF and PGE2 were found in both cases while IL-1 alpha was not detected. Both TNF and PGE2 levels were higher in the medium of the MdM infected with K biovars. TNF reached maximum levels 24 h postinfection, and then declined, while PGE2 levels increased continuously during the infection time up to 96 h post-infection. Addition of dexamethasone inhibited production of TNF and PGE2. Inhibition of PGE2 production by indomethacin resulted in increased production of TNF, while addition of PGE2 caused partial inhibition of TNF production from infected MdM

Predictability of oppositional defiant disorder and symptom dimensions in children and adolescents with ADHD combined type

Background Oppositional defiant disorder (ODD) is frequently co-occurring with attention deficit hyperactivity disorder (ADHD) in children and adolescents. Because ODD is a precursor of later conduct disorder (CD) and affective disorders, early diagnostic identification is warranted. Furthermore, the predictability of three recently confirmed ODD dimensions (ODD-irritable, ODD-headstrong and ODD-hurtful) may assist clinical decision making. Method Receiver-operating characteristic (ROC) analysis was used in order to test the diagnostic accuracy of the Conners' Parent Rating Scale revised (CPRS-R) and the parent version of the Strength and Difficulties Questionnaire (PSDQ) in the prediction of ODD in a transnational sample of 1093 subjects aged 5-17 years from the International Multicentre ADHD Genetics study. In a second step, the prediction of three ODD dimensions by the same parent rating scales was assessed by backward linear regression analyses. Results ROC analyses showed adequate diagnostic accuracy of the CPRS-R and the PSDQ in predicting ODD in this ADHD sample. Furthermore, the three-dimensional structure of ODD was confirmed by confirmatory factor analysis and the CPRS-R emotional lability scale significantly predicted the ODD irritable dimension. Conclusions The PSDQ and the CPRS-R are both suitable screening instruments in the identification of ODD. The emotional lability scale of the CPRS-R is an adequate predictor of irritability in youth referred for ADH

Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis largely owing to inefficient diagnosis and tenacious drug resistance. Activation of pancreatic stellate cells (PSCs) and consequent development of dense stroma are prominent features accounting for this aggressive biology1,2. The reciprocal interplay between PSCs and pancreatic cancer cells (PCCs) not only enhances tumour progression and metastasis but also sustains their own activation, facilitating a vicious cycle to exacerbate tumorigenesis and drug resistance3-7. Furthermore, PSC activation occurs very early during PDAC tumorigenesis8-10, and activated PSCs comprise a substantial fraction of the tumour mass, providing a rich source of readily detectable factors. Therefore, we hypothesized that the communication between PSCs and PCCs could be an exploitable target to develop effective strategies for PDAC therapy and diagnosis. Here, starting with a systematic proteomic investigation of secreted disease mediators and underlying molecular mechanisms, we reveal that leukaemia inhibitory factor (LIF) is a key paracrine factor from activated PSCs acting on cancer cells. Both pharmacologic LIF blockade and genetic Lifr deletion markedly slow tumour progression and augment the efficacy of chemotherapy to prolong survival of PDAC mouse models, mainly by modulating cancer cell differentiation and epithelial-mesenchymal transition status. Moreover, in both mouse models and human PDAC, aberrant production of LIF in the pancreas is restricted to pathological conditions and correlates with PDAC pathogenesis, and changes in the levels of circulating LIF correlate well with tumour response to therapy. Collectively, these findings reveal a function of LIF in PDAC tumorigenesis, and suggest its translational potential as an attractive therapeutic target and circulating marker. Our studies underscore how a better understanding of cell-cell communication within the tumour microenvironment can suggest novel strategies for cancer therapy

The generation of phase differences and frequency changes in a network model of inferior olive subthreshold oscillations

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedicationIt is commonly accepted that the Inferior Olive (IO) provides a timing signal to the cerebellum. Stable subthreshold oscillations in the IO can facilitate accurate timing by phase-locking spikes to the peaks of the oscillation. Several theoretical models accounting for the synchronized subthreshold oscillations have been proposed, however, two experimental observations remain an enigma. The first is the observation of frequent alterations in the frequency of the oscillations. The second is the observation of constant phase differences between simultaneously recorded neurons. In order to account for these two observations we constructed a canonical network model based on anatomical and physiological data from the IO. The constructed network is characterized by clustering of neurons with similar conductance densities, and by electrical coupling between neurons. Neurons inside a cluster are densely connected with weak strengths, while neurons belonging to different clusters are sparsely connected with stronger connections. We found that this type of network can robustly display stable subthreshold oscillations. The overall frequency of the network changes with the strength of the inter-cluster connections, and phase differences occur between neurons of different clusters. Moreover, the phase differences provide a mechanistic explanation for the experimentally observed propagating waves of activity in the IO. We conclude that the architecture of the network of electrically coupled neurons in combination with modulation of the inter-cluster coupling strengths can account for the experimentally observed frequency changes and the phase differences.Peer reviewedFinal Published versio