Reproducibility and responsiveness of the Symptom Severity Scale and the hand and finger function subscale of the Dutch arthritis impact measurement scales (Dutch-AIMS2-HFF) in primary care patients with wrist or hand problems

BACKGROUND: To determine the clinimetric properties of two questionnaires assessing symptoms (Symptom Severity Scale) and physical functioning (hand and finger function subscale of the AIMS2) in a Dutch primary care population. METHODS: The first 84 participants in a 1-year follow-up study on the diagnosis and prognosis of hand and wrist problems completed the Symptom Severity Scale and the hand and finger function subscale of the Dutch-AIMS2 twice within 1 to 2 weeks. The data were used to assess test-retest reliability (ICC) and smallest detectable change (SDC, based on the standard error of measurement (SEM)). To assess responsiveness, changes in scores between baseline and the 3 month follow-up were related to an external criterion to estimate the minimal important change (MIC). We calculated the group size needed to detect the MIC beyond measurement error. RESULTS: The ICC for the Symptom Severity Scale was 0.68 (95% CI: 0.54–0.78). The SDC was 1.00 at individual level and 0.11 at group level, both on a 5-point scale. The MIC was 0.23, exceeding the SDC at group level. The group size required to detect a MIC beyond measurement error was 19 for the Symptom Severity Scale. The ICC for the hand and finger function subscale of the Dutch-AIMS2 was 0.62 (95% CI: 0.47–0.74). The SDC was 3.80 at individual level and 0.42 at group level, both on an 11-point scale. The MIC was 0.31, which was less than the SDC at group level. The group size required to detect a MIC beyond measurement error was 150. CONCLUSION: In our heterogeneous primary care population the Symptom Severity Scale was found to be a suitable instrument to assess the severity of symptoms, whereas the hand and finger function subscale of the Dutch-AIMS2 was less suitable for the measurement of physical functioning in patients with hand and wrist problems

Positivity, entanglement entropy, and minimal surfaces

The path integral representation for the Renyi entanglement entropies of integer index n implies these information measures define operator correlation functions in QFT. We analyze whether the limit $n\rightarrow 1$, corresponding to the entanglement entropy, can also be represented in terms of a path integral with insertions on the region's boundary, at first order in $n-1$. This conjecture has been used in the literature in several occasions, and specially in an attempt to prove the Ryu-Takayanagi holographic entanglement entropy formula. We show it leads to conditional positivity of the entropy correlation matrices, which is equivalent to an infinite series of polynomial inequalities for the entropies in QFT or the areas of minimal surfaces representing the entanglement entropy in the AdS-CFT context. We check these inequalities in several examples. No counterexample is found in the few known exact results for the entanglement entropy in QFT. The inequalities are also remarkable satisfied for several classes of minimal surfaces but we find counterexamples corresponding to more complicated geometries. We develop some analytic tools to test the inequalities, and as a byproduct, we show that positivity for the correlation functions is a local property when supplemented with analyticity. We also review general aspects of positivity for large N theories and Wilson loops in AdS-CFT.Comment: 36 pages, 10 figures. Changes in presentation and discussion of Wilson loops. Conclusions regarding entanglement entropy unchange

Social interaction, noise and antibiotic-mediated switches in the intestinal microbiota

The intestinal microbiota plays important roles in digestion and resistance against entero-pathogens. As with other ecosystems, its species composition is resilient against small disturbances but strong perturbations such as antibiotics can affect the consortium dramatically. Antibiotic cessation does not necessarily restore pre-treatment conditions and disturbed microbiota are often susceptible to pathogen invasion. Here we propose a mathematical model to explain how antibiotic-mediated switches in the microbiota composition can result from simple social interactions between antibiotic-tolerant and antibiotic-sensitive bacterial groups. We build a two-species (e.g. two functional-groups) model and identify regions of domination by antibiotic-sensitive or antibiotic-tolerant bacteria, as well as a region of multistability where domination by either group is possible. Using a new framework that we derived from statistical physics, we calculate the duration of each microbiota composition state. This is shown to depend on the balance between random fluctuations in the bacterial densities and the strength of microbial interactions. The singular value decomposition of recent metagenomic data confirms our assumption of grouping microbes as antibiotic-tolerant or antibiotic-sensitive in response to a single antibiotic. Our methodology can be extended to multiple bacterial groups and thus it provides an ecological formalism to help interpret the present surge in microbiome data.Comment: 20 pages, 5 figures accepted for publication in Plos Comp Bio. Supplementary video and information availabl

Autonomous Targeting of Infectious Superspreaders Using Engineered Transmissible Therapies

Infectious disease treatments, both pharmaceutical and vaccine, face three universal challenges: the difficulty of targeting treatments to high-risk ‘superspreader’ populations who drive the great majority of disease spread, behavioral barriers in the host population (such as poor compliance and risk disinhibition), and the evolution of pathogen resistance. Here, we describe a proposed intervention that would overcome these challenges by capitalizing upon Therapeutic Interfering Particles (TIPs) that are engineered to replicate conditionally in the presence of the pathogen and spread between individuals — analogous to ‘transmissible immunization’ that occurs with live-attenuated vaccines (but without the potential for reversion to virulence). Building on analyses of HIV field data from sub-Saharan Africa, we construct a multi-scale model, beginning at the single-cell level, to predict the effect of TIPs on individual patient viral loads and ultimately population-level disease prevalence. Our results show that a TIP, engineered with properties based on a recent HIV gene-therapy trial, could stably lower HIV/AIDS prevalence by ∼30-fold within 50 years and could complement current therapies. In contrast, optimistic antiretroviral therapy or vaccination campaigns alone could only lower HIV/AIDS prevalence by <2-fold over 50 years. The TIP's efficacy arises from its exploitation of the same risk factors as the pathogen, allowing it to autonomously penetrate superspreader populations, maintain efficacy despite behavioral disinhibition, and limit viral resistance. While demonstrated here for HIV, the TIP concept could apply broadly to many viral infectious diseases and would represent a new paradigm for disease control, away from pathogen eradication but toward robust disease suppression

The Spin Structure of the Nucleon

We present an overview of recent experimental and theoretical advances in our understanding of the spin structure of protons and neutrons.Comment: 84 pages, 29 figure

Explaining the willingness of public professionals to implement new policies: A policy alienation framework

Nowadays, many public policies focus on economic values, such as efficiency and client choice. Public professionals often show resistance to implementing such policies. We analyse this problem using an interdisciplinary approach. From public administration, we draw on the policy alienation concept, which consists of five dimensions: strategic powerlessness, tactical powerlessness, operational powerlessness, societal meaninglessness and client meaninglessness. These are considered as factors that influence the willingness of professionals to implement policies (change willingness - a concept drawn from the change management literature). We test this model in a survey among 478 Dutch healthcare professionals implementing a new reimbursement policy. The first finding was that perceived autonomy (operational powerlessness) significantly influenced change willingness, whereas strategic and tactical powerlessness were not found to be significant. Second, both the meaninglessness dimensions proved highly significant. We conclude that clarifying the value of a policy is important in getting professionals to willingly implement a policy, whereas their participation on the strategic or tactical levels seems less of a motivational factor. These insights help in understanding why public professionals embrace or resist the implementation of particular policies. Points for practitioners Policymakers develop public policies which, nowadays, tend to focus strongly on economic values, such as increasing efficiency or offering citizens the opportunity to choose among suppliers of public services. Public professionals, who have to implement these policies, are often reluctant to do so. This study shows that the causes of this resistance are unlikely to be found in the lack of influence these professionals have in the shaping of the policy at the national or organizational level. Rather, professionals might resist implementing policies because they do not see them as meaningful for society, or for their own clients. Therefore, policymakers should focus on this perceived meaninglessness and adopt ways to counter this, for example by intensively communicating the value associated with a policy

Assessing health-related quality of life in patients with inflammatory bowel disease, in Crete, Greece

BACKGROUND: Health Related Quality of Life (HRQoL) is an important outcome measure in Inflammatory Bowel Disease (IBD). The aim of our study was to assess HRQoL in a population of 135 Greek patients with IBD. METHODS: A cohort of 135 patients with IBD, 81 with ulcerative colitis (UC) and 54 with Crohn's disease (CD) were enrolled in our study. Demographic and disease-related data were recorded. HRQoL was assessed by a disease-specific and a generic questionnaire, IBDQ and SF-36, respectively. Disease activity was assessed by Harvey-Bradshaw Index and the Colitis Activity Index for CD and UC patients, respectively. RESULTS: Among all variables recorded in our study, only disease activity had a significant effect on HRQoL. Patients with active disease scored significantly lower on both IBDQ and SF-36 when compared to those in remission. Only two among the four IBDQ dimensions, bowel and systemic, had significant ability in distinguishing best patients in remission from those with active disease. CONCLUSIONS: IBD has a negative impact on HRQoL. Patients with active disease are more impaired than patients in remission. In our population of patients bowel and systemic dimensions had a predominant value in patients' perception of quality of life. Patients in our study using the same instrument scored higher than previously reported

Renal dysfunction is associated with shorter telomere length in heart failure

Renal dysfunction is a frequent comorbidity associated with high mortality in patients with chronic heart failure (CHF). The intrinsic biological age might affect the ability of the kidney to cope with the challenging environment caused by CHF. We explored the association between leukocyte telomere length, a marker for biological age, and renal function in patients with CHF. Telomere length was determined by a real-time quantitative polymerase chain reaction in 866 CHF patients. Renal function was estimated with the simplified Modification of Diet in Renal Disease equation. The median age was 74 (interquartile range 64-79) years, 61% male, left ventricular ejection fraction of 30 (23-44)%, and the estimated glomerular filtration rate was 53 (40-68) ml/min/1.73 m(2). Telomere length was associated with renal function (correlation coefficient 0.123, P <0.001). This relationship remained significant after adjustment for age, gender, age of CHF onset (standardized-beta 0.091, P = 0.007). Also additionally adjusting for the severity of CHF and baseline differences did not change our findings. The association between shorter leukocyte telomere length and reduced renal function in heart failure suggests that intrinsic biological aging affects the ability of the kidney to cope with the systemic changes evoked by heart failure