The relationship between deprivation, tumour stage and the systemic inflammatory response in patients with primary operable breast cancer

The extent of deprivation (Carstairs deprivation index) was directly associated with the magnitude of the systemic inflammatory response (reduced albumin and elevated C-reactive protein, P<0.01) in patients with primary operable breast cancer (n=314). Deprivation was not associated with age, tumour size, tumour type, grade, and the proportion of patients with involved lymph nodes and oestrogen receptor status

Neurofilament Light Chain Related to Longitudinal Decline in Frontotemporal Lobar Degeneration

OBJECTIVE: Accurate diagnosis and prognosis of frontotemporal lobar degeneration (FTLD) during life is an urgent concern in the context of emerging disease-modifying treatment trials. Few CSF markers have been validated longitudinally in patients with known pathology, and we hypothesized that CSF neurofilament light chain (NfL) would be associated with longitudinal cognitive decline in patients with known FTLD-TAR DNA binding protein ~43kD (TDP) pathology. METHODS: This case-control study evaluated CSF NfL, total tau, phosphorylated tau, and β-amyloid1-42 in patients with known FTLD-tau or FTLD-TDP pathology (n = 50) and healthy controls (n = 65) and an extended cohort of clinically diagnosed patients with likely FTLD-tau or FTLD-TDP (n = 148). Regression analyses related CSF analytes to longitudinal cognitive decline (follow-up ∼1 year), controlling for demographic variables and core AD CSF analytes. RESULTS: In FTLD-TDP with known pathology, CSF NfL is significantly elevated compared with controls and significantly associated with longitudinal decline on specific executive and language measures, after controlling for age, disease duration, and core AD CSF analytes. Similar findings are found in the extended cohort, also including clinically identified likely FTLD-TDP. Although CSF NfL is elevated in FTLD-tau compared with controls, the association between NfL and longitudinal cognitive decline is limited to executive measures. CONCLUSION: CSF NfL is associated with longitudinal clinical decline in relevant cognitive domains in patients with FTLD-TDP after controlling for demographic factors and core AD CSF analytes and may also be related to longitudinal decline in executive functioning in FTLD-tau

Attenuated cerebrospinal fluid leukocyte count and sepsis in adults with pneumococcal meningitis: a prospective cohort study

BACKGROUND: A low cerebrospinal fluid (CSF) white-blood cell count (WBC) has been identified as an independent risk factor for adverse outcome in adults with bacterial meningitis. Whereas a low CSF WBC indicates the presence of sepsis with early meningitis in patients with meningococcal infections, the relation between CSF WBC and outcome in patients with pneumococcal meningitis is not understood. METHODS: We examined the relation between CSF WBC, bacteraemia and sepsis in a prospective cohort study that included 352 episodes of pneumococcal meningitis, confirmed by CSF culture, occurring in patients aged >16 years. RESULTS: CSF WBC was recorded in 320 of 352 episodes (91%). Median CSF WBC was 2530 per mm(3 )(interquartile range 531–6983 per mm(3)) and 104 patients (33%) had a CSF WBC <1000/mm(3). Patients with a CSF WBC <1000/mm(3 )were more likely to have an unfavourable outcome (defined as a Glasgow Outcome Scale score of 1–4) than those with a higher WBC (74 of 104 [71%] vs. 87 of 216 [43%]; P < 0.001). CSF WBC was significantly associated with blood WBC (Spearman's test 0.29), CSF protein level (0.20), thrombocyte count (0.21), erythrocyte sedimentation rate (-0.15), and C-reactive protein levels (-0.18). Patients with a CSF WBC <1000/mm(3 )more often had a positive blood culture (72 of 84 [86%] vs. 138 of 196 [70%]; P = 0.01) and more often developed systemic complications (cardiorespiratory failure, sepsis) than those with a higher WBC (53 of 104 [51%] vs. 69 of 216 [32%]; P = 0.001). In a multivariate analysis, advanced age (Odds ratio per 10-year increments 1.22, 95%CI 1.02–1.45), a positive blood culture (Odds ratio 2.46, 95%CI 1.17–5.14), and a low thrombocyte count on admission (Odds ratio per 100,000/mm(3 )increments 0.67, 95% CI 0.47–0.97) were associated with a CSF WBC <1000/mm(3). CONCLUSION: A low CSF WBC in adults with pneumococcal meningitis is related to the presence of signs of sepsis and systemic complications. Invasive pneumococcal infections should possibly be regarded as a continuum from meningitis to sepsis

Multilevel latent class casemix modelling: a novel approach to accommodate patient casemix

<p>Abstract</p> <p>Background</p> <p>Using routinely collected patient data we explore the utility of multilevel latent class (MLLC) models to adjust for patient casemix and rank Trust performance. We contrast this with ranks derived from Trust standardised mortality ratios (SMRs).</p> <p>Methods</p> <p>Patients with colorectal cancer diagnosed between 1998 and 2004 and resident in Northern and Yorkshire regions were identified from the cancer registry database (n = 24,640). Patient age, sex, stage-at-diagnosis (Dukes), and Trust of diagnosis/treatment were extracted. Socioeconomic background was derived using the Townsend Index. Outcome was survival at 3 years after diagnosis. MLLC-modelled and SMR-generated Trust ranks were compared.</p> <p>Results</p> <p>Patients were assigned to two classes of similar size: one with reasonable prognosis (63.0% died within 3 years), and one with better prognosis (39.3% died within 3 years). In patient class one, all patients diagnosed at stage B or C died within 3 years; in patient class two, all patients diagnosed at stage A, B or C survived. Trusts were assigned two classes with 51.3% and 53.2% of patients respectively dying within 3 years. Differences in the ranked Trust performance between the MLLC model and SMRs were all within estimated 95% CIs.</p> <p>Conclusions</p> <p>A novel approach to casemix adjustment is illustrated, ranking Trust performance whilst facilitating the evaluation of factors associated with the patient journey (e.g. treatments) and factors associated with the processes of healthcare delivery (e.g. delays). Further research can demonstrate the value of modelling patient pathways and evaluating healthcare processes across provider institutions.</p

Entropy-driven liquid-liquid separation in supercooled water

Twenty years ago Poole et al. (Nature 360, 324, 1992) suggested that the anomalous properties of supercooled water may be caused by a critical point that terminates a line of liquid-liquid separation of lower-density and higher-density water. Here we present an explicit thermodynamic model based on this hypothesis, which describes all available experimental data for supercooled water with better quality and with fewer adjustable parameters than any other model suggested so far. Liquid water at low temperatures is viewed as an 'athermal solution' of two molecular structures with different entropies and densities. Alternatively to popular models for water, in which the liquid-liquid separation is driven by energy, the phase separation in the athermal two-state water is driven by entropy upon increasing the pressure, while the critical temperature is defined by the 'reaction' equilibrium constant. In particular, the model predicts the location of density maxima at the locus of a near-constant fraction (about 0.12) of the lower-density structure.Comment: 7 pages, 6 figures. Version 2 contains an additional supplement with tables for the mean-field equatio

Climate-driven range extension of Amphistegina (protista, foraminiferida) : models of current and predicted future ranges

© The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS ONE 8 (2013): e54443, doi:10.1371/journal.pone.0054443.Species-range expansions are a predicted and realized consequence of global climate change. Climate warming and the poleward widening of the tropical belt have induced range shifts in a variety of marine and terrestrial species. Range expansions may have broad implications on native biota and ecosystem functioning as shifting species may perturb recipient communities. Larger symbiont-bearing foraminifera constitute ubiquitous and prominent components of shallow water ecosystems, and range shifts of these important protists are likely to trigger changes in ecosystem functioning. We have used historical and newly acquired occurrence records to compute current range shifts of Amphistegina spp., a larger symbiont-bearing foraminifera, along the eastern coastline of Africa and compare them to analogous range shifts currently observed in the Mediterranean Sea. The study provides new evidence that amphisteginid foraminifera are rapidly progressing southwestward, closely approaching Port Edward (South Africa) at 31°S. To project future species distributions, we applied a species distribution model (SDM) based on ecological niche constraints of current distribution ranges. Our model indicates that further warming is likely to cause a continued range extension, and predicts dispersal along nearly the entire southeastern coast of Africa. The average rates of amphisteginid range shift were computed between 8 and 2.7 km year−1, and are projected to lead to a total southward range expansion of 267 km, or 2.4° latitude, in the year 2100. Our results corroborate findings from the fossil record that some larger symbiont-bearing foraminifera cope well with rising water temperatures and are beneficiaries of global climate change.This work was supported by grants from the German Science Foundation (DFG; www.dfg.de) to ML and SL (LA 884/10-1, LA 884/5-1)