Tuberculin skin test reaction depends on type of purified protein derivative: implications for cut-off values.

SETTING: Due to purified protein derivative (PPD) RT23 stock-outs in 2014, PPD-Tubersol and PPD-Bulbio have been used for latent tuberculosis infection (LTBI) testing in the Netherlands.OBJECTIVE: To determine whether PPD-RT23, PPD-Tubersol and PPD-Bulbio were associated with differential indurations and confirmation using interferon-gamma release assays (IGRAs).DESIGN: LTBI surveillance data from 2013 to 2016 were extracted. Regression analyses were used to determine whether IGRA confirmation of TST-positive indurations depended on PPD, controlling for sex, age, incidence in country of origin, and bacille Calmette-Guérin (BCG) status.RESULTS: A total of 20 956 individuals were tested with PPD-RT23: 10 382 with PPD-Tubersol and 18 562 with PPD-Bulbio. Overall, 21% with PPD-Bulbio had an induration of ≥5 mm compared to 12% of those tested with PPD-RT23 and PPD-Tubersol. Compared to PPD-RT23, PPD-Bulbio indurations ≥5 mm were significantly less often IGRA-confirmed among contacts (aOR 1.3, 95% CI 1.1-1.6) and BCG-vaccinated immigrants (PPD-RT23, aOR 2.4, 95% CI 1.4-4.1). Increasing the PPD-Bulbio cut-off from ≥5 to ≥10 mm would save respectively 26%, 42%, and 35% of IGRAs among contacts, health care workers (HCWs) and BCG-vaccinated immigrants, with small absolute numbers of positive IGRAs missed (range 0-55 annually).CONCLUSION: PPD-Bulbio shows larger TST indurations than other PPDs, but is less often IGRA-confirmed. Increasing the TST cut-off from 5 to 10 mm prior to testing with an IGRA in HCWs and immigrants is recommended.

Are thrombocytopenia and platelet transfusions associated with major bleeding in preterm neonates? A systematic review.

Over 75% of severely thrombocytopenic preterm neonates receive platelet transfusions to prevent bleeding, but transfusion guidelines are based mainly on expert opinion. The aim of this review was to investigate whether platelet counts, platelet transfusions or platelet indices are associated with major bleeding in preterm neonates. We performed a systematic search of the EMBASE and MEDLINE databases until December 2017. We included randomized trials, cohort and case control studies. (Prospero: CRD42015013399). We screened 8734 abstracts and 1225 fulltexts, identifying 36 eligible studies. In 30, timing of the platelet counts or transfusions in relation to the bleeding was unclear. Of the remaining six studies, two showed that thrombocytopenia was associated with increased risk of bleeding, two showed no such assocation, and three showed lack of an association between platelet transfusions and bleeding risk. No studies assessing platelet indices were found. The study results suggest that prophylactic platelet transfusions may not reduce bleeding risk in preterm neonates.

The current total economic burden of diabetes mellitus in the Netherlands.

INTRODUCTION AND AIM: Insight into the total economic burden of diabetes mellitus (DM) is essential for decision makers and payers. Currently available estimates for the Netherlands only include part of the total burden or are no longer up-to-date. Therefore, this study aimed to determine the current total economic burden of DM and its complications in the Netherlands, by including all the relevant cost components. METHODS: The study combined a systematic literature review to identify all relevant published information and a targeted review to identify relevant information in the grey literature. The identified evidence was then combined to estimate the current total economic burden. RESULTS: In 2016, there were an estimated 1.1 million DM patients in the Netherlands, of whom approximately 10% had type 1 and 90% had type 2 DM. The estimated current total economic burden of DM was € 6.8 billion in 2016. Healthcare costs (excluding costs of complications) were € 1.6 billion, direct costs of complications were € 1.3 billion and indirect costs due to productivity losses, welfare payments and complications were € 4.0 billion. CONCLUSION: DM and its complications pose a substantial economic burden to the Netherlands, which is expected to rise due to changing demographics and lifestyle. Indirect costs, such as welfare payments, accounted for a large portion of the current total economic burden of DM, while these cost components are often not included in cost estimations. Publicly available data for key cost drivers such as complications were scarce.

Localized states influence spin transport in epitaxial graphene.

We developed a spin transport model for a diffusive channel with coupled localized states that result in an effective increase of spin precession frequencies and a reduction of spin relaxation times in the system. We apply this model to Hanle spin precession measurements obtained on monolayer epitaxial graphene on SiC(0001). Combined with newly performed measurements on quasi-free-standing monolayer epitaxial graphene on SiC(0001) our analysis shows that the different values for the diffusion coefficient measured in charge and spin transport measurements on monolayer epitaxial graphene on SiC(0001) and the high values for the spin relaxation time can be explained by the influence of localized states arising from the buffer layer at the interface between the graphene and the SiC surface.

Ribavirin rather than PEG-interferon pharmacodynamics predict nonresponse to antiviral therapy in naive chronic hepatitis C patients.

Twenty to fifty per cent of patients with chronic hepatitis C (CHC) experience nonresponse to current antiviral therapy, which may relate in part to ribavirin or PEG-interferon pharmacodynamics. We evaluated potential relevance of various factors for nonresponse. Two hundred forty-two naive CHC patients who received in a previous trial at least 24 weeks of antiviral therapy, including PEG-interferon alfa-2b and ribavirin, were analysed. Of them, 53% were infected with hepatitis C virus (HCV) genotype 1-4, 71% exhibited high viral load and 32% had severe fibrosis/cirrhosis. After 24 weeks of treatment, 39 patients (16%) were nonresponders. In multivariate analysis, lower serum ribavirin concentrations, HCV genotype 1-4 and higher baseline γ-GT predicted nonresponse. Week-24 ribavirin concentrations (2.2 vs 2.8 mg/L, P < 0.001), average ribavirin doses (14.5 vs 15.2 mg/kg per day, P = 0.03) and week-24 haemoglobin decreases (1.7 vs 2.0 mm, P = 0.02) were lower in nonresponders. Nonresponse rates increased progressively at decreasing ribavirin concentrations: 4%, 11%, 13% and 36% in case of serum ribavirin concentrations ≥4, 3-4, 2-3 and ≤2 mg/L, respectively (P = 0.001). Ribavirin concentrations correlated with both week-24 haemoglobin decreases (r = 0.42, P < 0.001) and ribavirin doses (r = 0.17, P = 0.01). Subgroup analysis in HCV genotype 1-4 patients revealed essentially the same results. Nonresponse was exceptional in HCV genotype 2-3 patients and associated with ribavirin concentrations <2 mg/L. Presumed interferon-related factors (average PEG-interferon doses and decreases in leucocytes, granulocytes, platelets and body weight) did not differ between nonresponders and responders. In conclusion, ribavirin- rather than PEG-interferon-related factors are independent and potentially modifiable predictors of nonresponse in treatment-naive CHC patients.

Coverage and yield of tuberculosis contact investigations in the Netherlands.

SETTING: An increasing proportion of tuberculosis (TB) patients in low-incidence countries are immigrants. It is unclear whether contact investigations among immigrant patients are adequate. OBJECTIVE: To determine whether ethnicity of pulmonary TB patients was associated with coverage and yield of contact investigations in the Netherlands. DESIGN: Contact investigation results were extracted from records of patients reported in the nationwide surveillance register in 2006 and 2007. Prevalence odds ratios (PORs) with 95% confidence intervals (CIs) were calculated to determine the association between patient ethnicity and coverage of contact investigations and the yield of individuals with Mycobacterium tuberculosis infection or TB. RESULTS: Of the 1040 pulmonary TB patients reported, 642 (62%) were eligible for analysis. Compared to close contacts of Dutch patients, close contacts of immigrant patients were significantly less likely to be examined for TB (89% vs. 93%, POR 0.6, 95%CI 0.5-0.7) and infection (50% vs. 75%, POR 0.3, 95%CI 0.3-0.4), whereas the yield was significantly higher for disease (1.5% vs. 0.4%, POR 3.4, 95%CI 1.8-6.4) and infection (13% vs. 10%, POR 1.2, 95%CI 1.0-1.5). CONCLUSION: The effectiveness of contact investigations in the Netherlands can be optimised by expanding the investigation of contacts of immigrant patients.

Internal stresses, normal modes, and nonaffinity in three-dimensional biopolymer networks.

We numerically investigate deformations and modes of networks of semiflexible biopolymers as a function of crosslink coordination number z and strength of bending and stretching energies. In equilibrium filaments are under internal stress, and the networks exhibit shear rigidity below the Maxwell isostatic point. In contrast to two-dimensional networks, ours exhibit nonaffine bending-dominated response in all rigid states, including those near the maximum of z=4 when bending energies are less than stretching ones.

Semiflexible filamentous composites.

Inspired by the ubiquity of composite filamentous networks in nature, we investigate models of biopolymer networks that consist of interconnected floppy and stiff filaments. Numerical simulations carried out in three dimensions allow us to explore the microscopic partitioning of stresses and strains between the stiff and floppy fractions cs and cf and reveal a nontrivial relationship between the mechanical behavior and the relative fraction of stiff polymer: when there are few stiff polymers, nonpercolated stiff "inclusions" are protected from large deformations by an encompassing floppy matrix, while at higher fractions of stiff material the stiff network is independently percolated and dominates the mechanical response.

Frequency-dependent stiffening of semiflexible networks: a dynamical nonaffine to affine transition.

By combining the force-extension relation of single semiflexible polymers with a Langevin equation to capture the dissipative dynamics of chains moving through a viscous medium we study the dynamical response of cross-linked biopolymer materials. We find that at low frequencies the network deformations are highly nonaffine, and show a low plateau in the modulus. At higher frequencies, this nonaffinity decreases while the elastic modulus increases. With increasing frequency, more and more nonaffine network relaxation modes are suppressed, resulting in a stiffening. This effect is fundamentally different from the high-frequency stiffening due to the single-filament relaxation modes [F. Gittes and F. C. MacKintosh, Phys. Rev. E 58, R1241 (1998)], not only in terms of its mechanism but also in its resultant scaling: G'(ω) ∼ ω(α) with α > 3/4. This may determine nonlinear material properties at low, physiologically relevant frequencies.

Universal scaling in highly doped conducting polymer films.

Electrical transport of a highly doped disordered conducting polymer, viz. poly-3,4-ethylenedioxythiophene stabilized with poly-4-styrenesulphonic acid, is investigated as a function of bias and temperature. The transport shows universal power-law scaling with both bias and temperature. All measurements constitute a single universal curve, and the complete J(V,T) characteristics are described by a single equation. We relate this scaling to dissipative tunneling processes, such as Coulomb blockade.

Monte Carlo study of multiply crosslinked semiflexible polymer networks.

We present a method to generate realistic, three-dimensional networks of crosslinked semiflexible polymers. The free energy of these networks is obtained from the force-extension characteristics of the individual polymers and their persistent directionality through the crosslinks. A Monte Carlo scheme is employed to obtain isotropic, homogeneous networks that minimize the free energy and for which all of the relevant parameters can be varied: the persistence length and the contour length as well as the crosslinking length may be chosen at will. We also provide an initial survey of the mechanical properties of our networks subjected to shear strains, showing them to display the expected nonlinear stiffening behavior. Also, a key role for nonaffinity and its relation to order in the network is uncovered.

Single atom adhesion in optimized gold nanojunctions.

We study the interaction between single apex atoms in a metallic contact, using the break junction geometry. By carefully training our samples, we create stable junctions in which no further atomic reorganization takes place. This allows us to study the relation between the so-called jump out of contact (from contact to tunneling regime) and jump to contact (from tunneling to contact regime) in detail. Our data can be fully understood within a relatively simple elastic model, where the elasticity k of the electrodes is the only free parameter. We find 5

Effect of fat digestion on superior mesenteric artery blood flow in humans.

BACKGROUND AND AIM: Intraluminal nutrients stimulate superior mesenteric artery (SMA) blood flow. Of the macronutrients, especially fat affects the magnitude of the SMA blood flow response to a meal. Little is known however on the influence of fat hydrolysis on SMA flow. METHODS: We compared in eight healthy volunteers the SMA flow response (Doppler ultrasonography) to continuous intraduodenal fat perfusion (LCT, 240 kCal h(-1)) during conditions with normal hydrolysis (placebo, control), increased hydrolysis (pancreatic enzyme supplementation; 50 kU lipase) and impaired hydrolysis (orlistat 240 mg). RESULTS: Intraduodenal LCT significantly (P<0.01) increased SMA flow in all experiments over basal. The SMA flow response to fat during pancreatic enzyme supplementation (1.49 +/- 0.1 l min(-1)) was significantly (P<0.05) higher compared with placebo (1.11 +/- 0.16 l min(-1)). Lipase inhibition with orlistat did not significantly affect fat stimulated SMA flow compared with placebo: 0.89 +/- 0.08 l min(-1) versus 1.11 +/- 0.16 l min(-1). CONCLUSIONS: Administration of pancreatic enzymes significantly increases fat stimulated SMA flow. Fat digest products in the intestinal lumen contribute to the regulation of SMA blood flow.

Three-dimensional cross-linked F-actin networks: relation between network architecture and mechanical behavior.

Numerical simulations are reported for the response of three-dimensional cross-linked F-actin networks when subjected to large deformations. In addition to the physiological parameters such as actin and cross-linker concentration, the model explicitly accounts for filament properties and network architecture. Complementary to two-dimensional studies, we find that the strain-stiffening characteristics depend on network architecture through the local topology around cross-links.

Tropical agricultural residues and their potential uses in fish feeds: the Costa Rican situation.

In Costa Rica as many other tropical countries, the disposal problem of agricultural wastes is widely recognized but efforts to find solutions are not equal for different sectors. This study describes the situation of major agricultural residues in Costa Rica, identifying the activities with higher amounts produced and, the potential use of these residues in fish feeds. In Costa Rica, during the 1993-1994 production season, major agricultural sectors (crop and livestock) generated a total amount of 3.15-3.25 million MT of residues (classified in by-products: used residues and wastes: not used residues). Some residues are treated to turn them into valuable items or to diminish their polluting effects (e.g., the so-called by-products). About 1.56-1.63 million MT of by-products were used for different purposes (e.g. fertilization, animal feeding, fuel, substrates in greenhouses). However, the remainder (1.59-1.62 million MT) was discharged into environment causing pollution. About 1.07-1.2 million MT wastes came from major crop systems (banana, coffee, sugarcane and oil palm) whereas the remainder came from animal production systems (porcine and poultry production, slaughtering). These data are further compared to residues estimates for the 2001-2002 production season coming from the biggest crops activities. Unfortunately, most of the studied wastes contain high levels of moisture and low levels of protein, and also contain variable amounts of antinutritional factors (e.g., polyphenols, tannins, caffeine), high fibre levels and some toxic substances and pesticides. All these reasons may limit the use of these agricultural wastes for animal feeding, especially in fish feeds. The potential use of the major vegetable and animal residues in fish feeds is discussed based on their nutritional composition, on their amount available over the year and on their pollution risks. Other constraints to use these wastes in fish feeds are the extra costs of drying and, in most cases, of transportation from several dispersed locations. It was stated that most interesting wastes are rejected green banana and coffee pulp.

Misrouted olfactory fibres and ectopic olfactory glomeruli in normal humans and in Parkinson and Alzheimer patients.

The presence and distribution of misrouted (MR) olfactory projection fibres were studied in the olfactory bulbs of control human brains and in the brains of people who had suffered from Parkinson's and Alzheimer's disease. It appeared that MR fibres, that is, fibres that terminate deep into the glomerular layer, are a common phenomenon in the bulbs of aged people. In all but one of the bulbs studied, MR fibres are present. The amount of MR fibres is not related to age. With a few exceptions, the MR fibres are restricted to the external plexiform layer (EPL). Only in Parkinson bulbs the MR fibres occasionally form glomerulus-like structures. These pseudo glomeruli are located in the EPL. It is concluded that MR olfactory projection fibres are a normal phenomenon in the human olfactory bulb. In nonhuman mammalians, MR fibres have only been observed in foetal and neonatal olfactory bulbs. Possibly, the age-related loss of mitral cells, which are the natural synaptic targets for the olfactory projection fibres, may play a role in the aberrant behaviour of the MR olfactory receptor cell axons. The ectopic glomerulus-like structures in Parkinson bulbs share some characteristics with normal rat glomeruli that are not observed in normal human olfactory glomeruli. This may refer to possible changes in the genetic content of olfactory structures in Parkinson patients.

Biological treatments affect the chemical composition of coffee pulp.

Biological treatments were applied to fresh coffee pulp (CoP) to improve its nutritive value for monogastric animals by reducing its content of cellulose and antinutritional factors (ANFs) such as total phenols, tannins and caffeine. Treatments were: (1) ensiling with 0, 50 and 100 gkg(-1) molasses for 2 and 3 months, (2) aerobic decomposition for 0, 7, 14, 21, 28, 35 and 42 days, (3) aerobic bacterial inoculation (Bacillus sp.) for 0, 7, 14, 21 and 28 days. Ensiled CoP (E-CoP) showed higher fat and ash contents than oven-dried-CoP (OD-CoP; P<0.05). Similarly, true protein values tended to increase. The cellulose and total phenols levels of E-CoP were lower than OD-CoP (P<0.05). The E-CoP tannins levels tended to be lower than OD-CoP whereas caffeine levels remained unaffected. Improvement in the nutritional quality of E-CoP was associated with higher fat and protein contents and reduction of cellulose, total phenols and tannins. The aerobic decomposition treatment improved the nutritional quality of CoP by increasing true protein and fat contents. In addition, total phenols, tannins, caffeine and cellulose contents were reduced by an increase in treatment time (P<0.05). Bacterial treatment increased the protein content of CoP after 21 days (from 137 to 392 gkg(-1)) and decreased it after 28 days. Cellulose, total phenols, tannins and caffeine contents reduced with an increase in time of bacterial degradation. Bacterial treatment improved the CoP quality by increasing protein content and reducing cellulose and ANFs, especially after 21 days of treatment. Both the aerobic decomposition (after 21-28 days) and the aerobic bacterial degradation of CoP (after 21 days) appeared more suitable to improve the nutritional quality of CoP than the ensiling.

Preliminary study on haemocyte response to white spot syndrome virus infection in black tiger shrimp Penaeus monodon.

White spot syndrome virus (WSSV) has been a major cause of shrimp mortality in aquaculture in the past decade. In contrast to extensive studies on the morphology and genome structure of the virus, little work has been done on the defence reaction of the host after WSSV infection. Therefore, we examined the haemocyte response to experimental WSSV infection in the black tiger shrimp Penaeus monodon. Haemolymph sampling and histology showed a significant decline in free, circulating haemocytes after WSSV infection. A combination of in situ hybridisation with a specific DNA probe for WSSV and immuno-histochemistry with a specific antibody against haemocyte granules in tissue sections indicated that haemocytes left the circulation and migrated to tissues where many virus-infected cells were present. However, no subsequent haemocyte response to the virus-infected cells was detected. The number of granular cells decreased in the haematopoietic tissue of infected shrimp. In addition, a fibrous-like immuno-reactive layer appears in the outer stromal matrix of tubule walls in the lymphoid organ of infected shrimp. The role of haemocytes in shrimp defence after viral infection is discussed.