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We evaluated the effects of fermentation time and acid casein content on the microbial rennet obtained by solid-state fermentation using wheat bran as the carbon source. The experiments used two fermentation times (72 and 96 h), while acid casein content was 1.5, 2.0, 2.5, and 3.0 g. Rennet strength from eight enzymatic extracts was measured using pasteurized whole milk. Rennet strength of samples from 72 h of fermentation showed an increase when acid casein content increased. The rennet strength increased at 96 h of fermentation with increasing amount of casein (up to 2.5 g), and then decreased with the largest addition (3.0 g) of casein. Coagulation time for the sample with highest rennet strength was 420 s.
Systematic reviews in mental health have become useful tools for health professionals in view of the massive amount and heterogeneous nature of biomedical information available today. In order to determine the risk of bias in the studies evaluated and to avoid bias in generalizing conclusions from the reviews it is therefore important to use a very strict methodology in systematic reviews. One bias which may affect the generalization of results is publication bias, which is determined by the nature and direction of the study results. To control or minimize this type of bias, the authors of systematic reviews undertake comprehensive searches of medical databases and expand on the findings, often undertaking searches of grey literature (material which is not formally published). This paper attempts to show the consequences (and risk) of generalizing the implications of grey literature in the control of publication bias, as was proposed in a recent systematic work. By repeating the analyses for the same outcome from three different systematic reviews that included both published and grey literature our results showed that confusion between grey literature and publication bias may affect the results of a concrete meta-analysis.
To assess antipsychotic medication in the treatment of schizophrenia, based on trial drop-out rates.
Methods
The studies included were randomised controlled trials that compared any of the four clinically best-established atypical antipsychotics (quetiapine, olanzapine, risperidone or clozapine) against either of two typical antipsychotics regarded as the gold standard (haloperidol or chlorpromazine).
Results
Meta-analysis indicated less risk of all-cause patient withdrawal from atypical medication trials where dosage was flexible, in both the short, relative risk (RR) 0.70 (95% CI 0.64–0.76), P < 0.00001, and long term, RR 0.72 (0.65–0.80), P < 0.00001. Similar results were observed for withdrawal due to adverse events, RR: 0.54 (0.41–0.72), P < 0.0001. Nevertheless, the favourable effects of atypical medication disappeared in trials relying on fixed dosage.
Conclusions
We detected a significant positive effect in terms of the outcome of treatment discontinuation for atypical versus typical medication, though only where the use of flexible rather than fixed doses (closer to an experimental control situation) was possible.
The presence of at least five dimensions in mania has recently been established. This study extends previous findings by comparing the dimensions of pure vs. mixed mania.
Materials and method
One hundred and three inpatients with bipolar I disorder, manic or mixed (DSM IV), were assessed with SCID-I, YMRS and HDRS-21. The five-factor solution found after applying factorial analysis with Varimax rotation was compared between manic and mixed patients.
Results
There were differences between pure mania and mixed states on factor 1 (depression) and factor 3 (hedonism). There was a tendency to present higher values on factor 5 (activation) in the pure manic group. No differences were found in factor 2 (dysphoria) and factor 4 (psychosis).
Discussion
Hedonism and activation dimensions are present to a lesser degree in mixed states. Although the principal difference between mixed and pure bipolar disorder is the existence of depressive symptoms, the depressive dimension is strongly present in patients with pure mania.
Conclusions
There is need to search for core depressive symptoms in all patients suffering from mania and to evaluate their outcome in clinical trials.
Evidence-informed planning and interpretation of research results both require standardised description of local care delivery context. Such context analysis descriptions should be comparable across regions and countries to allow benchmarking and organizational learning, and for research findings to be interpreted in context. The European Service Mapping Schedule (ESMS) is a classification of adult mental health services that was later adapted for the assessment of health and social systems research (Description and Evaluation of Services and DirectoriEs - DESDE). The aim of the study was to review the diffusion and use of the ESMS/DESDE system in health and social care and its impact in health policy and decision-making.
Method.
We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (1997–2018).
Results.
Out of 155 papers mentioning ESMS/DESDE, 71 have used it for service research and planning. The classification has been translated into eight languages and has been used by seven international research networks. Since 2000, it has originated 11 instruments for health system research with extensive analysis of their metric properties. The ESMS/DESDE coding system has been used in 585 catchment areas in 34 countries for description of services delivery at local, regional and national levels.
Conclusions.
The ESMS/DESDE system provides a common terminology, a classification of care services, and a set of tools allowing a variety of aims to be addressed in healthcare and health systems research. It facilitates comparisons across and within countries for evidence-informed planning.
We consider de Finetti’s problem for spectrally one-sided Lévy risk models with control strategies that are absolutely continuous with respect to the Lebesgue measure. Furthermore, we consider the version with a constraint on the time of ruin. To characterize the solution to the aforementioned models, we first solve the optimal dividend problem with a terminal value at ruin and show the optimality of threshold strategies. Next, we introduce the dual Lagrangian problem and show that the complementary slackness conditions are satisfied, characterizing the optimal Lagrange multiplier. Finally, we illustrate our findings with a series of numerical examples.
Conclusions and recommendations of health technology assessment (HTA) reports have an impact on all relevant actors involved in the health system (health authorities, administrators, health professionals, patients, citizens and industry). The involvement of all those relevant stakeholders in the HTA process facilitates making valid and informed decisions and an efficient allocation of resources. Improving communication, participation and transparency among all agents will lead to more efficient evaluation and decision-making processes.
Methods
To review key aspects of the relations between HTA agencies and health industries, two process were carried out: a narrative review of literature searched in Medline, PubMed, Embase, CINAHL and WOS (2007-2017) and a review of websites of international HTA agencies. References and webs with information on the framework, objectives, methodologies, impact or results of the relationships were included.
Results
A total of 1961 references were located and forty-five were selected. From the synthesis of the selected references the following key aspects of the relationships between HTA and industry were identified: (i) the importance of early dialogues with industry to align HTA objectives with the generation of evidence; (ii) challenges of the bias in the evidence produced by industry; (iii) difficulties in industry engagement in HTA processes; and (iv) industry interest in HTA. The review of six agency websites provided information on industry involvement in strategic activities, early dialogues, provision of documentation, management of industry clarifications, review of the report/allegations and other forms of relationship.
Conclusions
Both the review of the literature and the contents of the web pages of international agencies with experience in relations with industry show that the interest is in the creation of collaborative frameworks between regulatory authorities that decide on authorization and price and reimbursement and HTA agencies, while both try to maintain an early, transparent and systematic interaction with the healthcare industry.
De Finetti’s optimal dividend problem has recently been extended to the case when dividend payments can be made only at Poisson arrival times. In this paper we consider the version with bail-outs where the surplus must be nonnegative uniformly in time. For a general spectrally negative Lévy model, we show the optimality of a Parisian-classical reflection strategy that pays the excess above a given barrier at each Poisson arrival time and also reflects from below at 0 in the classical sense.
To investigate whether amnestic mild cognitive impairment (aMCI) identified with visual memory tests conveys an increased risk of Alzheimer’s disease (risk-AD) and if the risk-AD differs from that associated with aMCI based on verbal memory tests.
Participants:
4,771 participants aged 70.76 (SD = 6.74, 45.4% females) from five community-based studies, each a member of the international COSMIC consortium and from a different country, were classified as having normal cognition (NC) or one of visual, verbal, or combined (visual and verbal) aMCI using international criteria and followed for an average of 2.48 years. Hazard ratios (HR) and individual patient data (IPD) meta-analysis analyzed the risk-AD with age, sex, education, single/multiple domain aMCI, and Mini-Mental State Examination (MMSE) scores as covariates.
Results:
All aMCI groups (n = 760) had a greater risk-AD than NC (n = 4,011; HR range = 3.66 – 9.25). The risk-AD was not different between visual (n = 208, 17 converters) and verbal aMCI (n = 449, 29 converters, HR = 1.70, 95%CI: 0.88, 3.27, p = 0.111). Combined aMCI (n = 103, 12 converters, HR = 2.34, 95%CI: 1.13, 4.84, p = 0.023) had a higher risk-AD than verbal aMCI. Age and MMSE scores were related to the risk-AD. The IPD meta-analyses replicated these results, though with slightly lower HR estimates (HR range = 3.68, 7.43) for aMCI vs. NC.
Conclusions:
Although verbal aMCI was most common, a significant proportion of participants had visual-only or combined visual and verbal aMCI. Compared with verbal aMCI, the risk-AD was the same for visual aMCI and higher for combined aMCI. Our results highlight the importance of including both verbal and visual memory tests in neuropsychological assessments to more reliably identify aMCI.
Gilding threads collected from Spanish and Portuguese palaces and from the embroideries and adornments of sculptures of the Virgin and Christ that form part of Sevillian Holy Week were analyzed and compared (20 artifacts were evaluated). The study covered a broad time period with examples from the 13th to 14th centuries, 18th to 20th centuries, and also including modern embroideries. A combination of scanning electron microscopy and energy-dispersive X-ray spectroscopy was used. The knowledge of the layered structures of the threads has provided very valuable information regarding the manufacturing techniques. The different metal threads found in the embroidery studied consisted of gold, silver, copper, and alloys of these metals and aluminium. The fabrication procedures often differed in the different workshops and changed with time. In the modern embroideries, a decrease of precious metal concentration was detected. The threads were wound around a core of silk threads.
In this Research Communication we assessed factors affecting colostrum quality of dairy Lacaune ewes using the Brix-refractometer. Colostrum from 536 lambings from one commercial intensive dairy Lacaune farm were analysed for the following factors with potential influence in colostrum quality: (1) ewe parity (n = 84–132), (2) length of previous dry period (PDP) (n = 23–214), (3) age at first lambing (AFL) of primiparous ewes (n = 9–88), (4) lambing season (n = 192 or 344), and (5) year (2011–2013, n = 142–203). Parity significantly affected colostrum quality, with primiparous ewes showing the highest Brix refractometer values (22·6 ± 5·6%, P < 0·0001), though values were similar among multiparous ewes. PDP length also significantly affected colostrum quality: ewes with the shortest PDP showed the worst quality (16·8 ± 4·2%, P < 0·0001), with quality gradually rising with PDP length. Colostrum quality was significantly higher in 2011 (21·0 ± 5·2%) than in 2012 or 2013 (P < 0·0001); this likely reflects the several-fold greater proportion of animals with long PDP in 2011. In contrast, neither AFL nor lambing season significantly affected colostrum quality. These results suggest that parity and PDP length can substantially affect ovine colostrum quality of dairy ewes under intensive management conditions and they further show the usefulness of the Brix refractometer for providing a rough estimation of colostrum quality on-farm. However, further studies are needed to determine a validated cut-off Brix value for identifying good-quality colostra in ovine species.
Here we present a new site in the Sierra de Atapuerca (Burgos, Spain): Galería de las Estatuas (GE), which provides new information about Mousterian occupations in the Iberian Plateau. The GE was an ancient entrance to the cave system, which is currently closed and sealed by a stalagmitic crust, below which a detritic sedimentary sequence of more than 2 m is found. This has been divided into five litostratigraphic units with a rich assemblage of faunal and lithic remains of clear Mousterian affinity. Radiocarbon dates provide minimum ages and suggest occupations older than 45 14C ka BP. The palynological analysis detected a landscape change to increased tree coverage, which suggests that the sequence recorded a warming episode. The macromammal assemblage is composed of both ungulates (mainly red deer and equids) and carnivores. Taphonomic analysis reveals both anthropic, and to a lesser extent, carnivore activities. The GE was occupied by Neanderthals and also sporadically by carnivores. This new site broadens the information available regarding different human occupations at the Sierra de Atapuerca, which emphasizes the importance of this site-complex for understanding human evolution in Western Europe.
We study the dual model with capital injection under the additional condition that the dividend strategy is absolutely continuous. We consider a refraction–reflection strategy that pays dividends at the maximal rate whenever the surplus is above a certain threshold, while capital is injected so that it stays non-negative. The resulting controlled surplus process becomes the spectrally positive version of the refracted–reflected process recently studied by Pérez and Yamazaki (2015). We study various fluctuation identities of this process and prove the optimality of the refraction–reflection strategy. Numerical results on the optimal dividend problem are also given.
Inspired by the works of Landriault et al. (2011), (2014), we study the Gerber–Shiu distribution at Parisian ruin with exponential implementation delays for a spectrally negative Lévy insurance risk process. To be more specific, we study the so-called Gerber–Shiu distribution for a ruin model where at each time the surplus process goes negative, an independent exponential clock is started. If the clock rings before the surplus becomes positive again then the insurance company is ruined. Our methodology uses excursion theory for spectrally negative Lévy processes and relies on the theory of so-called scale functions. In particular, we extend the recent results of Landriault et al. (2011), (2014).
By using strontium isotopic ratios of dental enamel from molars, we were able to reconstruct the migration context for three individuals of a Columbian mammoth population (Mammuthus columbi) around Laguna de las Cruces, San Luis Potosí, central México. A three-step leaching procedure was applied to eliminate secondary Sr contributions in the molar enamel. One of the studied individuals showed 87Sr/86Sr ratios similar to those obtained from soils and plants from Laguna de las Cruces and was identified as local, whereas the other two mammoths had different molar 87Sr/86Sr values, indicative of migration and mobility contexts.
Magnetic nanoparticles (MNPs) are a class of materials that can be manipulated under the influence of an external magnetic field. Thanks to the ability of the MNPs to be guided by an external magnetic field that is like "action at a distance", combined with their low cytotoxicity and the intrinsic penetrability of magnetic fields into human tissue, opens up many applications involving the transport and/or immobilization of biological entities [1, 2].
This work is focused on the synthesis of magnetite nanoparticles by varied methods, their functionalization with nickel tetrasulfonated phthalocyanine, and the corresponding physicochemical characterization and colloidal stability studies in biologically compatible media. The in vitro production of singlet oxygen by these nanoparticles through photochemical stimulation in ultraviolet and visible region was evaluated, resulting in 4.5 and 4 µM respectly to magnetite synthetized in the group. The increase reactive oxygen species concentration in the cellular environment can result in modification and damage of cellular components, and potentially, cell death and necrosis. Therefore, these materials offer the promise of revolutionary tools for photodynamic therapy and hyperthermia, which are attractive strategies for cancer therapy without systemic toxicity.
Coeliac disease (CD) is an immune-mediated enteropathy resulting from exposure to gluten in genetically predisposed individuals. Gluten proteins are partially digested by human proteases generating immunogenic peptides that cause inflammation in patients carrying HLA-DQ2 and DQ8 genes. Although intestinal dysbiosis has been associated with patients with CD, bacterial metabolism of gluten has not been studied in depth thus far. The aim of this study was to analyse the metabolic activity of intestinal bacteria associated with gluten intake in healthy individuals, CD patients and first-degree relatives of CD patients. Faecal samples belonging to twenty-two untreated CD patients, twenty treated CD patients, sixteen healthy volunteers on normal diet, eleven healthy volunteers on gluten-free diet (GFD), seventy-one relatives of CD patients on normal diet and sixty-nine relatives on GFD were tested for several proteolytic activities, cultivable bacteria involved in gluten metabolism, SCFA and the amount of gluten in faeces. We detected faecal peptidasic activity against the gluten-derived peptide 33-mer. CD patients showed differences in faecal glutenasic activity (FGA), faecal tryptic activity (FTA), SCFA and faecal gluten content with respect to healthy volunteers. Alterations in specific bacterial groups metabolising gluten such as Clostridium or Lactobacillus were reported in CD patients. Relatives showed similar parameters to CD patients (SCFA) and healthy volunteers (FTA and FGA). Our data support the fact that commensal microbial activity is an important factor in the metabolism of gluten proteins and that this activity is altered in CD patients.
During Early, as proposed by the International commission on stratigraphy Pleistocene times, interacting fluvial and aeolian processes constructed wide alluvial plains over an evaporite-dominated Miocene substratum in the central Ebro Basin. An exceptional site where these deposits show faults, folds, diapirs, karst structures and unconformities has been studied in detail. Analysis of particular structures demonstrates the interaction by that time of tectonic faulting, diapirism, karstification and sedimentation in an area where deformation was traditionally linked to the presence of underlying evaporites, without proposing any precise mechanism. Multiple approaches (sedimentology, structural geology and geophysics) have been used in order to discriminate the origin of each type of structure as well as to understand the interaction between different processes. Numerous normal faults and fractures of variable size are consistent with the regional stress field. Pleistocene deposits are pierced by diapirs of Miocene evaporites and disrupted by karst structures with different geometries (tubular, funnel and vault), both partially controlled by tectonics. The example described is proposed as an analogue model that could successfully illustrate evolution patterns of basins of potential interest for petroleum geology where similar processes have actuated, resulting in complex stratigraphical architectures.
Arid regions are increasingly being anthropogenically altered. In the north-western Sahara, a growing road network facilitates the use of habitats adjacent to roads. In regions where livestock is the traditional and main economic resource, local people are currently building numerous water cisterns for watering livestock, leading to an increase in the extent of pasturing of domestic livestock. Cisterns may attract desert vertebrates and act as death traps for species with already sparse populations in these arid areas. This paper is the first to examine the impact of cisterns as lethal traps for amphibians and reptiles in the Sahara, using a survey of 823 cisterns in south-western Morocco to identify and quantify species affected. Four amphibians and 35 reptiles were trapped in cisterns, some of which were listed as threatened. At least 459 017 individual amphibians and reptiles were trapped annually within the study area. The low productivity and low population densities of terrestrial vertebrates in this arid region suggest cisterns have a substantial impact upon amphibian and reptile species. As cistern construction is increasing, management actions are required to mitigate this impact on the herpetological community.
Slope deposits in semiarid regions are known to be very sensitive environments, especially those that occurred during the minor fluctuations of the late Holocene. In this paper we analyse Holocene colluvium genesis, composition, and paleoenvironmental meaning through the study of slope deposits in NE Spain. Two cumulative slope stages are described during this period. In the study area, both slope accumulations are superimposed and this has enabled an excellent preservation of the aggregative sequence and the paleosols corresponding to stabilisation stages. 14C and TL dating, as well as archaeological remains, provide considerable chronological precision for this sequence. The origin of the accumulation of the lower unit is placed around 4295–4083 cal yr BP/2346–2134 cal yr BC (late Chalcolithic) and it developed until the Iron Age in a cooler and wetter climate (Cold Iron Age). Under favourable conditions, a soil A-horizon was formed on top of this unit. A new slope accumulation was formed during the Little Ice Age. Within the slope two morphogenetic periods ending with A-horizons are distinguished and related with two main cold–wet climatic events. The study of these slopes provides a great amount of data for the paleoenvironmental and geoarchaeological reconstruction of the late Holocene in NE Spain.