Can falls risk prediction tools correctly identify fall-prone elderly rehabilitation inpatients? A systematic review and meta-analysis

Background Falls of elderly people may cause permanent disability or death. Particularly susceptible are elderly patients in rehabilitation hospitals. We systematically reviewed the literature to identify falls prediction tools available for assessing elderly inpatients in rehabilitation hospitals. Methods and Findings We searched six electronic databases using comprehensive search strategies developed for each database. Estimates of sensitivity and specificity were plotted in ROC space graphs and pooled across studies. Our search identified three studies which assessed the prediction properties of falls prediction tools in a total of 754 elderly inpatients in rehabilitation hospitals. Only the STRATIFY tool was assessed in all three studies; the other identified tools (PJC-FRAT and DOWNTON) were assessed by a single study. For a STRATIFY cut-score of two, pooled sensitivity was 73% (95%CI 63 to 81%) and pooled specificity was 42% (95%CI 34 to 51%). An indirect comparison of the tools across studies indicated that the DOWNTON tool has the highest sensitivity (92%), while the PJC-FRAT offers the best balance between sensitivity and specificity (73% and 75%, respectively). All studies presented major methodological limitations. Conclusions We did not identify any tool which had an optimal balance between sensitivity and specificity, or which were clearly better than a simple clinical judgment of risk of falling. The limited number of identified studies with major methodological limitations impairs sound conclusions on the usefulness of falls risk prediction tools in geriatric rehabilitation hospitals.

Pneumococcal meningitis causes accumulation of neurotoxic kynurenine metabolites in brain regions prone to injury

Pneumococcal meningitis (PM) is characterized by an intense inflammatory host reaction that contributes to the development of cortical necrosis and hippocampal apoptosis. Inflammatory conditions in the brain are known to induce tryptophan degradation along the kynurenine pathway, resulting in accumulation of neurotoxic metabolites. In the present study, we investigated the contribution of the kynurenine pathway to brain injury in experimental PM by measuring the concentration of its metabolites and the enzymatic activities and mRNA levels of its major enzymes in the vulnerable brain regions. In the late phase of acute PM, we found a significant transcriptional upregulation of kynurenine-3-hydroxylase and an accumulation of the neurotoxic metabolites 3-hydroxykynurenine (3-HKYN) and 3-hydroxyanthranilic acid in cortex and hippocampus. The positive correlation between the concentration of 3-HKYN and the extent of hippocampal apoptosis adds support to the concept that 3-HKYN contributes to brain injury in PM.

Impaired vascular function in normoglycemic mice prone to autoimmune diabetes: role of nitric oxide

Type 1 diabetes is an immuno-inflammatory condition which increases the risk of cardiovascular disease, particularly in young adults. This study investigated whether vascular function is altered in mice prone to autoimmune diabetes and whether the nitric oxide (NO)-cyclic GMP axis is involved. Aortic rings suspended in organ chambers and precontracted with phenylephrine were exposed to cumulative concentrations of acetylcholine. To investigate the role of NO, some experiments were performed in the presence of either 1400W (N-(3-aminomethyl)benzyl-acetamidine hydrochloride), a selective inhibitor of the iNOS-isoform, L-NAME (N(G)-nitro-L-arginine methyl ester hydrochloride), an inhibitor of all three NOS-isoforms, or ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), a selective inhibitor of guanylate cyclase. Moreover, contractility to phenylephrine, big endothelin-1, and endothelin-1 was assessed and histological analysis and iNOS immunohistochemistry were performed. Endothelium-dependent relaxation was reduced in prediabetic NOD mice (78+/-4 vs. 88+/-2%, respectively, P<0.05 vs. control) despite normal plasma glucose levels (n.s. vs. control). Preincubation with 1400W further attenuated responses in prediabetic (P<0.05 vs. untreated) but not in diabetic or in control mice. In contrast, basal NO bioactivity remained unaffected until the onset of diabetes in NOD mice. Contractile responses to big endothelin-1 and endothelin-1 were reduced in prediabetic animals (P<0.05 vs. control), whereas in diabetic mice only responses to big endothelin-1 were decreased (P<0.05 vs. control). These data demonstrate that endothelium-dependent and -independent vascular function in NOD mice is abnormal already in prediabetes in the absence of structural injury. Early proinflammatory activation due to iNOS in diabetes-prone NOD mice appears to be one of the mechanisms contributing to impaired vasoreactivity.

A quantitative analysis of microcirculation in sore-prone pressure areas on conventional and pressure relief hospital mattresses using laser Doppler flowmetry and tissue spectrophotometry

BACKGROUND Pressure ulcers are associated with severe impairment for the patients and high economic load. With this study we wanted to gain more insight to the skin perfusion dynamics due to external loading. Furthermore, we evaluated the effect of different types of pressure relief mattresses. METHODS A total of 25 healthy volunteers were enrolled in the study. Perfusion dynamics of the sacral and the heel area were assessed using the O2C-device, which combines a laser light, to determine blood flow, and white light to determine the relative amount of hemoglobin. Three mattresses were evaluated compared to a hard surface: a standard hospital foam mattress bed, a visco-elastic foam mattress, and an air-fluidized bed. RESULTS In the heel area, only the air-fluidized bed was able to maintain the blood circulation (mean blood flow of 13.6 ± 6 versus 3.9 ± 3 AU and mean relative amount of hemoglobin of 44.0 ± 14 versus 32.7 ± 12 AU.) In the sacral area, all used mattresses revealed an improvement of blood circulation compared to the hard surface. CONCLUSION The results of this study form a more precise pattern of perfusion changes due to external loading on various pressure relief mattresses. This knowledge may reduce the incidence of pressure ulcers and may be an influencing factor in pressure relief mattress selection.

Increased bone mineral density at the hypoxia prone site of the juxta-articular metacarpal bone in patients with limited systemic sclerosis: a cross-sectional study

OBJECTIVES Low levels of oxygen has been shown to be involved in the induction of osteogenesis, particularly in bone repair. It is unknown whether hypoxia leads to osteogenesis at the hypoxia prone skeletal sites in limited systemic sclerosis. This study determined the total and trabecular volumetric bone mineral density (vBMD) at the hypoxia prone site of the juxta-articular metacarpal bone. METHODS In this cross-sectional study, female patients with limited systemic sclerosis were included and compared to healthy controls. Peripheral quantitative computed tomography was used to measure cross-sectional area, total vBMD, and trabecular vBMD at the radius, the tibia and the third metacarpal bone. Disease severity was assessed by the modified Rodnan Skin Score. RESULTS Twenty consecutive patients were included in the sclerosis group and 20 in the control group. Mean age was 60 years (range 52-68 years), and mean disease duration was 45 months (range 4-156 months). Age, height, and weight were comparable between the groups. The mean modified Rodnan Skin Score was 1.78 (range 0 to 8). The sclerosis group showed both higher total and trabecular vBMD at the distal metacarpal bone (p=0.05 and 0.04, respectively). vBMD of the tibia and radius did not differ in both groups. CONCLUSIONS vBMD at the juxta-articular metacarpal bone in patients with limited systemic sclerosis is increased, possibly due to an alteration in local bone metabolism and hypoxia induced local osteogenesis.

How much management is enough? Stakeholder views on forest management in fire-prone areas in central Portugal

With the increasing pressure to improve the contribution of forests to help dealing with global changes, it is critical to understand the different perceptions of those involved in the forest. How do forest owners, managers and members of local communities who often depend on the forest, value it and what are the problems affecting the forests in terms of being able to meet these new challenges? In Portugal, this task has taken on an even greater priority as more than 90% of the forest is private and forest management relies on the individual decisions of thousands of forest owners. To understand stakeholder views on forest and forest management, a transversal social perception survey was implemented in the form of a case study of central Portugal which included decision-makers, local technicians, forest owners and the general public. The results show that there is a consensus on the main issues affecting forests and forest management. A shift from classic forest owners to the emergence of indifferent forest owners was observed, although this shift has not been recognized by the forest owners in the survey, who maintain the individual management of their properties.

A mathematical model of a criminal-prone society

Criminals are common to all societies. To fight against them the community takes different security measures as, for example, to bring about a police. Thus, crime causes a depletion of the common wealth not only by criminal acts but also because the cost of hiring a police force. In this paper, we present a mathematical model of a criminal-prone self-protected society that is divided into socio-economical classes. We study the effect of a non-null crime rate on a free-of-criminals society which is taken as a reference system. As a consequence, we define a criminal-prone society as one whose free-of-criminals steady state is unstable under small perturbations of a certain socio-economical context. Finally, we compare two alternative strategies to control crime: (i) enhancing police efficiency, either by enlarging its size or by updating its technology, against (ii) either reducing criminal appealing or promoting social classes at risk

The Advantage of Arriving First: Characteristic Times in Finite Size Populations of Error-Prone Replicators

We study the evolution of a finite size population formed by mutationally isolated lineages of error-prone replicators in a two-peak fitness landscape. Computer simulations are performed to gain a stochastic description of the system dynamics. More specifically, for different population sizes, we compute the probability of each lineage being selected in terms of their mutation rates and the amplification factors of the fittest phenotypes. We interpret the results as the compromise between the characteristic time a lineage takes to reach its fittest phenotype by crossing the neutral valley and the selective value of the sequences that form the lineages. A main conclusion is drawn: for finite population sizes, the survival probability of the lineage that arrives first to the fittest phenotype rises significantly

Agreement Abstractions in Anonymous and Homonymous Distributed Systems Prone to Failures

The distributed computing models typically assume every process in the system has a distinct identifier (ID) or each process is programmed differently, which is named as eponymous system. In such kind of distributed systems, the unique ID is helpful to solve problems: it can be incorporated into messages to make them trackable (i.e., to or from which process they are sent) to facilitate the message transmission; several problems (leader election, consensus, etc.) can be solved without the information of network property in priori if processes have unique IDs; messages in the register of one process will not be overwritten by others process if this process announces; it is useful to break the symmetry. Hence, eponymous systems have influenced the distributed computing community significantly either in theory or in practice. However, every thing in the world has its own two sides. The unique ID also has disadvantages: it can leak information of the network(size); processes in the system have no privacy; assign unique ID is costly in bulk-production(e.g, sensors). Hence, homonymous system is appeared. If some processes share the same ID and programmed identically is called homonymous system. Furthermore, if all processes shared the same ID or have no ID is named as anonymous system. In homonymous or anonymous distributed systems, the symmetry problem (i.e., how to distinguish messages sent from which process) is the main obstacle in the design of algorithms. This thesis is aimed to propose different symmetry break methods (e.g., random function, counting technique, etc.) to solve agreement problem. Agreement is a fundamental problem in distributed computing including a family of abstractions. In this thesis, we mainly focus on the design of consensus, set agreement, broadcast algorithms in anonymous and homonymous distributed systems. Firstly, the fault-tolerant broadcast abstraction is studied in anonymous systems with reliable or fair lossy communication channels separately. Two classes of anonymous failure detectors AΘ and AP∗ are proposed, and both of them together with a already proposed failure detector ψ are implemented and used to enrich the system model to implement broadcast abstraction. Then, in the study of the consensus abstraction, it is proved the AΩ′ failure detector class is strictly weaker than AΩ and AΩ′ is implementable. The first implementation of consensus in anonymous asynchronous distributed systems augmented with AΩ′ and where a majority of processes does not crash. Finally, a general consensus problem– k-set agreement is researched and the weakest failure detector L used to solve it, in asynchronous message passing systems where processes may crash and recover, with homonyms (i.e., processes may have equal identities), and without a complete initial knowledge of the membership.

Agreement Abstractions in Anonymous and Homonymous Distributed Systems Prone to Failures

The distributed computing models typically assume every process in the system has a distinct identifier (ID) or each process is programmed differently, which is named as eponymous system. In such kind of distributed systems, the unique ID is helpful to solve problems: it can be incorporated into messages to make them trackable (i.e., to or from which process they are sent) to facilitate the message transmission; several problems (leader election, consensus, etc.) can be solved without the information of network property in priori if processes have unique IDs; messages in the register of one process will not be overwritten by others process if this process announces; it is useful to break the symmetry. Hence, eponymous systems have influenced the distributed computing community significantly either in theory or in practice. However, every thing in the world has its own two sides. The unique ID also has disadvantages: it can leak information of the network(size); processes in the system have no privacy; assign unique ID is costly in bulk-production(e.g, sensors). Hence, homonymous system is appeared. If some processes share the same ID and programmed identically is called homonymous system. Furthermore, if all processes shared the same ID or have no ID is named as anonymous system. In homonymous or anonymous distributed systems, the symmetry problem (i.e., how to distinguish messages sent from which process) is the main obstacle in the design of algorithms. This thesis is aimed to propose different symmetry break methods (e.g., random function, counting technique, etc.) to solve agreement problem. Agreement is a fundamental problem in distributed computing including a family of abstractions. In this thesis, we mainly focus on the design of consensus, set agreement, broadcast algorithms in anonymous and homonymous distributed systems. Firstly, the fault-tolerant broadcast abstraction is studied in anonymous systems with reliable or fair lossy communication channels separately. Two classes of anonymous failure detectors AΘ and AP∗ are proposed, and both of them together with a already proposed failure detector ψ are implemented and used to enrich the system model to implement broadcast abstraction. Then, in the study of the consensus abstraction, it is proved the AΩ′ failure detector class is strictly weaker than AΩ and AΩ′ is implementable. The first implementation of consensus in anonymous asynchronous distributed systems augmented with AΩ′ and where a majority of processes does not crash. Finally, a general consensus problem– k-set agreement is researched and the weakest failure detector L used to solve it, in asynchronous message passing systems where processes may crash and recover, with homonyms (i.e., processes may have equal identities), and without a complete initial knowledge of the membership.

Role of lipid polymorphism in G protein-membrane interactions: Nonlamellar-prone phospholipids and peripheral protein binding to membranes

Heterotrimeric G proteins (peripheral proteins) conduct signals from membrane receptors (integral proteins) to regulatory proteins localized to various cellular compartments. They are in excess over any G protein-coupled receptor type on the cell membrane, which is necessary for signal amplification. These facts account for the large number of G protein molecules bound to membrane lipids. Thus, the protein-lipid interactions are crucial for their cellular localization, and consequently for signal transduction. In this work, the binding of G protein subunits to model membranes (liposomes), formed with defined membrane lipids, has been studied. It is shown that although G protein α-subunits were able to bind to lipid bilayers, the presence of nonlamellar-prone phospholipids (phosphatidylethanolamines) enhanced their binding to model membranes. This mechanism also appears to be used by other (structurally and functionally unrelated) peripheral proteins, such as protein kinase C and the insect protein apolipophorin III, indicating that it could constitute a general mode of protein-lipid interactions, relevant in the activity and translocation of some peripheral (amphitropic) proteins from soluble to particulate compartments. Other factors, such as the presence of cholesterol or the vesicle surface charge, also modulated the binding of the G protein subunits to lipid bilayers. Conversely, the binding of G protein-coupled receptor kinase 2 and the G protein β-subunit to liposomes was not increased by hexagonally prone lipids. Their distinct interactions with membrane lipids may, in part, explain the different cellular localizations of all of these proteins during the signaling process.

Expression of error-prone polymerases in BL2 cells activated for Ig somatic hypermutation

High affinity antibodies are generated in mice and humans by means of somatic hypermutation (SHM) of variable (V) regions of Ig genes. Mutations with rates of 10−5–10−3 per base pair per generation, about 106-fold above normal, are targeted primarily at V-region hot spots by unknown mechanisms. We have measured mRNA expression of DNA polymerases ι, η, and ζ by using cultured Burkitt's lymphoma (BL)2 cells. These cells exhibit 5–10-fold increases in heavy-chain V-region mutations targeted only predominantly to RGYW (R = A or G, Y = C or T, W = T or A) hot spots if costimulated with T cells and IgM crosslinking, the presumed in vivo requirements for SHM. An ∼4-fold increase pol ι mRNA occurs within 12 h when cocultured with T cells and surface IgM crosslinking. Induction of pols η and ζ occur with T cells, IgM crosslinking, or both stimuli. The fidelity of pol ι was measured at RGYW hot- and non-hot-spot sequences situated at nicks, gaps, and double-strand breaks. Pol ι formed T⋅G mispairs at a frequency of 10−2, consistent with SHM-generated C to T transitions, with a 3-fold increased error rate in hot- vs. non-hot-spot sequences for the single-nucleotide overhang. The T cell and IgM crosslinking-dependent induction of pol ι at 12 h may indicate an SHM “triggering” event has occurred. However, pols ι, η, and ζ are present under all conditions, suggesting that their presence is not sufficient to generate mutations because both T cell and IgM stimuli are required for SHM induction.