Model-assisted predictions on prognosis in HNSCC: do we learn?

Dedicated software packages incorporating prognostic models are meant to aid physicians in making accurate predictions of prognosis. This study concerns 742 predictions of 5-year survival on consecutive newly diagnosed patients with head- and neck squamous cell carcinoma. The 5-year survival predictions made by the physicians are not compared with actual survival, but with a prediction made by OncologIQ, a dedicated software package. We used a linear regression and a linear mixed-effects model to look at absolute differences between both predictions and possible learning effects. Predictions made by the physicians were optimistic and inaccurate. Using the linear regression and linear mixed-effects models, the physicians’ learning effect showed little improvement per successive prediction. We conclude that prognostic predictions in general are imprecise. When given feedback on the model’s predicted survival, the accuracy increases, but only very modestly

Mycobacterium africanum—Review of an Important Cause of Human Tuberculosis in West Africa

Mycobacterium africanum consists of two phylogenetically distinct lineages within the Mycobacterium tuberculosis complex, known as M. africanum West African 1 and M. africanum West African 2. These lineages are restricted to West Africa, where they cause up to half of human pulmonary tuberculosis. In this review we discuss the definition of M. africanum, describe the prevalence and restricted geographical distribution of M. africanum West African 1 and 2, review the occurrence of M. africanum in animals, and summarize the phenotypic differences described thus far between M. africanum and M. tuberculosis sensu stricto

Complexity of the Tensegrity Structure for Dynamic Energy and Force Distribution of Cytoskeleton during Cell Spreading

Cytoskeleton plays important roles in intracellular force equilibrium and extracellular force transmission from/to attaching substrate through focal adhesions (FAs). Numerical simulations of intracellular force distribution to describe dynamic cell behaviors are still limited. The tensegrity structure comprises tension-supporting cables and compression-supporting struts that represent the actin filament and microtubule respectively, and has many features consistent with living cells. To simulate the dynamics of intracellular force distribution and total stored energy during cell spreading, the present study employed different complexities of the tensegrity structures by using octahedron tensegrity (OT) and cuboctahedron tensegrity (COT). The spreading was simulated by assigning specific connection nodes for radial displacement and attachment to substrate to form FAs. The traction force on each FA was estimated by summarizing the force carried in sounding cytoskeletal elements. The OT structure consisted of 24 cables and 6 struts and had limitations soon after the beginning of spreading by declining energy stored in struts indicating the abolishment of compression in microtubules. The COT structure, double the amount of cables and struts than the OT structure, provided sufficient spreading area and expressed similar features with documented cell behaviors. The traction force pointed inward on peripheral FAs in the spread out COT structure. The complex structure in COT provided further investigation of various FA number during different spreading stages. Before the middle phase of spreading (half of maximum spreading area), cell attachment with 8 FAs obtained minimized cytoskeletal energy. The maximum number of 12 FAs in the COT structure was required to achieve further spreading. The stored energy in actin filaments increased as cells spread out, while the energy stored in microtubules increased at initial spreading, peaked in middle phase, and then declined as cells reached maximum spreading. The dynamic flows of energy in struts imply that microtubules contribute to structure stabilization

Low pH gel intranasal sprays inactivate influenza viruses in vitro and protect ferrets against influenza infection

<p>Abstract</p> <p>Background</p> <p>Developing strategies for controlling the severity of pandemic influenza is a global public health priority. In the event of a pandemic there may be a place for inexpensive, readily available, effective adjunctive therapies to support containment strategies such as prescription antivirals, vaccines, quarantine and restrictions on travel. Inactivation of virus in the intranasal environment is one possible approach. The work described here investigated the sensitivity of influenza viruses to low pH, and the activity of low pH nasal sprays on the course of an influenza infection in the ferret model.</p> <p>Methods</p> <p>Inactivation of influenza A and avian reassortment influenza was determined using <it>in vitro </it>solutions tests. Low pH nasal sprays were tested using the ferret model with an influenza A Sydney/5/97 challenge. Clinical measures were shed virus, weight loss and body temperature.</p> <p>Results</p> <p>The virus inactivation studies showed that influenza viruses are rapidly inactivated by contact with acid buffered solutions at pH 3.5. The titre of influenza A Sydney/5/97 [H3N2] was reduced by at least 3 log cycles with one minute contact with buffers based on simple acid mixtures such as L-pyroglutamic acid, succinic acid, citric acid and ascorbic acid. A pH 3.5 nasal gel composition containing pyroglutamic acid, succinic acid and zinc acetate reduced titres of influenza A Hong Kong/8/68 [H3N2] by 6 log cycles, and avian reassortment influenza A/Washington/897/80 X A Mallard/New York/6750/78 [H3N2] by 5 log cycles, with 1 min contact.</p> <p>Two ferret challenge studies, with influenza A Sydney/5/97, demonstrated a reduction in the severity of the disease with early application of low pH nasal sprays versus a saline control. In the first study there was decreased weight loss in the treatment groups. In the second study there were reductions in virus shedding and weight loss, most notably when a gelling agent was added to the low pH formulation.</p> <p>Conclusion</p> <p>These findings indicate the potential of a low pH nasal spray as an adjunct to current influenza therapies, and warrant further investigation in humans.</p

Serum macrophage migration inhibitory factor reflects adrenal function in the hypothalamo-pituitary-adrenal axis of septic patients: an observational study

<p>Abstract</p> <p>Background</p> <p>The hypothalamo-pituitary-adrenal (HPA) axis modulates the inflammatory response during sepsis. Macrophage migration inhibitory factor (MIF), which counteracts the anti-inflammatory activity of glucocorticoid (GC), is one of the mediators of the development of inflammation. An inflammatory imbalance involving GC and MIF might be the cause or result of adrenal insufficiency. Our objective was to clarify the relationship between serum MIF and adrenal function in the HPA axis of sepsis patients using the adrenocorticotropic hormone (ACTH) stimulation test.</p> <p>Methods</p> <p>An observational study was performed in a university intensive care unit over a two-year period. Of 64 consecutive sepsis patients, 41 were enrolled. The enrolled patients underwent an ACTH stimulation test within 24 h of the diagnosis of severe sepsis or septic shock. Clinical and laboratory parameters, including serum MIF and cortisol, were measured.</p> <p>Results</p> <p>Based on their responses to the ACTH stimulation test, the patients were divided into a normal adrenal response (NAR) group (n = 22) and an adrenal insufficiency (AI) group (n = 19). The AI group had significantly more septic shock patients and higher prothrombin time ratios, serum MIF, and baseline cortisol than did the NAR group (<it>P </it>< 0.05). Serum MIF correlated significantly with the SOFA (Sequential Organ Failure Assessment) score, prothrombin time ratio, and delta max cortisol, which is maximum increment of serum cortisol concentration after ACTH stimulation test (rs = 0.414, 0.355, and -0.49, respectively, <it>P </it>< 0.05). Serum MIF also correlated significantly with the delta max cortisol/albumin ratio (rs = -0.501, <it>P </it>= 0.001). Receiver operating characteristic curve analysis identified the threshold serum MIF concentration (19.5 ng/mL, <it>P </it>= 0.01) that segregated patients into the NAR and AI groups.</p> <p>Conclusions</p> <p>The inverse correlation between serum MIF and delta max cortisol or the delta max cortisol/albumin ratio suggests that high serum MIF reflects an insufficient adrenal response in the HPA axis. Serum MIF could be a valuable clinical marker of adrenal insufficiency in sepsis patients.</p

Congruence and diversity of butterfly-host plant associations at higher taxonomic levels

We aggregated data on butterfly-host plant associations from existing sources in order to address the following questions: (1) is there a general correlation between host diversity and butterfly species richness?, (2) has the evolution of host plant use followed consistent patterns across butterfly lineages?, (3) what is the common ancestral host plant for all butterfly lineages? The compilation included 44,148 records from 5,152 butterfly species (28.6% of worldwide species of Papilionoidea) and 1,193 genera (66.3%). The overwhelming majority of butterflies use angiosperms as host plants. Fabales is used by most species (1,007 spp.) from all seven butterfly families and most subfamilies, Poales is the second most frequently used order, but is mostly restricted to two species-rich subfamilies: Hesperiinae (56.5% of all Hesperiidae), and Satyrinae (42.6% of all Nymphalidae). We found a significant and strong correlation between host plant diversity and butterfly species richness. A global test for congruence (Parafit test) was sensitive to uncertainty in the butterfly cladogram, and suggests a mixed system with congruent associations between Papilionidae and magnoliids, Hesperiidae and monocots, and the remaining subfamilies with the eudicots (fabids and malvids), but also numerous random associations. The congruent associations are also recovered as the most probable ancestral states in each node using maximum likelihood methods. The shift from basal groups to eudicots appears to be more likely than the other way around, with the only exception being a Satyrine-clade within the Nymphalidae that feed on monocots. Our analysis contributes to the visualization of the complex pattern of interactions at superfamily level and provides a context to discuss the timing of changes in host plant utilization that might have promoted diversification in some butterfly lineages

Feasibility, reliability and validity of a questionnaire on healthcare consumption and productivity loss in patients with a psychiatric disorder (TiC-P)

Background: Patient self-report allows collecting comprehensive data for the purpose of performing economic evaluations. The aim of the current study was to assess the feasibility, reliability and a part of the construct validity of a commonly applied questionnaire on healthcare utilization and productivity losses in patients with a psychiatric disorder (TiC-P). Methods. Data were derived alongside two clinical trials performed in the Netherlands in patients with mental health problems. The response rate, average time of filling out the questionnaire and proportions of missing values were used as indicators of feasibility of the questionnaire. Test-retest analyses were performed including Cohen's kappa and intra class correlation coefficients to assess reliability of the data. The construct validity was assessed by comparing patient reported data on contacts with psychotherapists and reported data on long-term absence from work with data derived from registries. Results: The response rate was 72%. The mean time needed for filling out the first TiC-P was 9.4 minutes. The time needed for filling out the questionnaire was 2.3 minutes less for follow up measurements. Proportions of missing values were limited (< 2.4%) except for medication for which in 10% of the cases costs could not be calculated. Cohen's kappa was satisfactory to almost perfect for most items related to healthcare consumption and satisfactory for items on absence from work and presenteeism. Comparable results were shown by the ICCs on variables measuring volumes of medical consumption and productivity losses indicating good reliability of the questionnaire. Absolute agreement between patient-reported data and data derived from medical registrations of the psychotherapists was satisfactory. Accepting a margin o

Myocardial perfusion reserve and contractile pattern after beta-blocker therapy in patients with idiopathic dilated cardiomyopathy

In Idiopathic Dilated Cardiomyopathy (IDC) an imbalance between myocardial oxygen consumption and supply has been postulated. The ensuing subclinical myocardial ischemia may contribute to progressive deterioration of LV function. beta-blocker is the therapy of choice in these patients. However, not all patients respond to the same extent. The aim of this study was to elucidate whether differences between responders and non-responders can be identified with respect to regional myocardial perfusion reserve (MPR) and contractile performance. Patients with newly diagnosed IDC underwent Positron Emission Tomography (PET) scanning using both (13)N-ammonia as a perfusion tracer (baseline and dipyridamole stress), and (18)F-fluoro-deoxyglucose as a metabolism tracer, and a dobutamine stress MRI. MRI and PET were repeated 6 months after maximal beta-blocker therapy. MPR (assessed by PET) as well as wall motion score (WMS, assessed by MRI) were evaluated in a 17 segment-model. Functional response to beta-blocker therapy was assigned as a stable or improved LVEF or diminished LVEF. Sixteen patients were included (age 47.9 +/- A 11.5 years; 12 males, LVEF 28.6 +/- A 8.4%). Seven patients showed improved LVEF (9.7 +/- A 3.1%), and nine patients did not show improved LVEF (-3.4 +/- A 3.9%). MPR improved significantly in responders (1.56 +/- A .23 to 1.93 +/- A .49, P = .049), and MPR decreased in non-responders; however, not significantly (1.98 +/- A .70 to 1.61 +/- A .28, P = .064), but was significantly different between both groups (P = .017) after beta-blocker therapy. A significant correlation was found between change in perfusion reserve and change in LVEF: a decrease in perfusion reserve was associated with a decrease in LVEF and vice versa. Summed rest score of wall motion in responders improved from 26 to 21 (P = .022) whereas in non-responders no change was observed from 26 to 25) (P = ns). Summed stress score of wall motion in responders improved from 23 to 21 (P = .027) whereas in non-responders no change was observed from 27 to 26) (P = ns). In IDC patients, global as well as regional improvement after initiation of beta-blocker treatment is accompanied by an improvement in regional perfusion parameters. On the other hand in IDC patients with further left ventricular function deterioration after initiation of beta-blocker therapy this is accompanied by a decrease in perfusion reserve