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Steady two-dimensional fluid flow over an obstacle is solved using complex variable methods. We consider the cases of rectangular obstacles, such as large boulders, submerged in a potential flow. These may arise in geophysics, marine and civil engineering. Our models are applicable to initiation of motion that may result in subsequent transport. The local flow depends on the obstacle shape, slowing down in confining corners and speeding up in expanding corners. The flow generates hydrodynamic forces, drag and lift, and their associated moments, which differ around each face. Our model replaces the need for ill-defined drag and lift coefficients with geometry-dependent functions. We predict smaller flow velocities to initiate motion. We show how a joint-bound boulder can be transported against gravity, and analyse the influence of a wake region behind an isolated boulder.
Indirect comparisons via a common comparator (anchored comparisons) are commonly used in health technology assessment. However, common comparators may not be available, or the comparison may be biased due to differences in effect modifiers between the included studies. Recently proposed population adjustment methods aim to adjust for differences between study populations in the situation where individual patient data are available from at least one study, but not all studies. They can also be used when there is no common comparator or for single-arm studies (unanchored comparisons). We aim to characterise the use of population adjustment methods in technology appraisals (TAs) submitted to the United Kingdom National Institute for Health and Care Excellence (NICE).
We reviewed NICE TAs published between 01/01/2010 and 20/04/2018.
Population adjustment methods were used in 7 percent (18/268) of TAs. Most applications used unanchored comparisons (89 percent, 16/18), and were in oncology (83 percent, 15/18). Methods used included matching-adjusted indirect comparisons (89 percent, 16/18) and simulated treatment comparisons (17 percent, 3/18). Covariates were included based on: availability, expert opinion, effective sample size, statistical significance, or cross-validation. Larger treatment networks were commonplace (56 percent, 10/18), but current methods cannot account for this. Appraisal committees received results of population-adjusted analyses with caution and typically looked for greater cost effectiveness to minimise decision risk.
Population adjustment methods are becoming increasingly common in NICE TAs, although their impact on decisions has been limited to date. Further research is needed to improve upon current methods, and to investigate their properties in simulation studies.
Tuberculosis (TB) is the leading cause of death among infectious diseases worldwide. Among the estimated cases of drug-resistant TB, approximately 60% occur in the BRICS countries (Brazil, Russia, India, China and South Africa). Among Brazilian states, primary and acquired multidrug-resistant TB (MDR-TB) rates were the highest in Rio Grande do Sul (RS). This study aimed to perform molecular characterisation of MDR-TB in the State of RS, a high-burden Brazilian state. We performed molecular characterisation of MDR-TB cases in RS, defined by drug susceptibility testing, using 131 Mycobacterium tuberculosis (M.tb) DNA samples from the Central Laboratory. We carried out MIRU-VNTR 24loci, spoligotyping, sequencing of the katG, inhA and rpoB genes and RDRio sublineage identification. The most frequent families found were LAM (65.6%) and Haarlem (22.1%). RDRio deletion was observed in 42 (32%) of the M.tb isolates. Among MDR-TB cases, eight (6.1%) did not present mutations in the studied genes. In 116 (88.5%) M.tb isolates, we found mutations associated with rifampicin (RIF) resistance in rpoB gene, and in 112 isolates (85.5%), we observed mutations related to isoniazid resistance in katG and inhA genes. An insertion of 12 nucleotides (CCAGAACAACCC) at the 516 codon in the rpoB gene, possibly responsible for a decreased interaction of RIF and RNA polymerase, was found in 19/131 of the isolates, belonging mostly to LAM and Haarlem families. These results enable a better understanding of the dynamics of transmission and evolution of MDR-TB in the region.
Use of pneumococcal conjugate vaccines has caused emergence of non-vaccine serotypes. No Brazilian data specifically about serotype 19A are available. We aimed to evaluate the frequency of occurrence, susceptibility profile and molecular epidemiology of serotype 19A before and after vaccine introduction in Brazil. Pneumococcal identification was performed by the conventional method. Strain serotype was determined by multiplex polymerase chain reaction (PCR) and/or Quellung reaction. Resistance was determined by Etest® and PCR was performed to determine the presence of macrolide resistance genes, ermB and/or mefA. Pneumococci were typed by Multilocus Sequence Typing. Thirty-eight serotype 19A Streptococcus pneumoniae were recovered, mostly from invasive diseases. Prevalence of serotype 19A increased following vaccination (from 3.5% before vaccination to 8.1% after, p = 0.04196). Non-susceptibility increased to most antimicrobials after vaccine introduction and was associated with clonal complex (CC)320. MLST showed nine different STs, which were grouped in one main CC: CC320 (63.9%). During the post-vaccination era, the frequency of this serotype increased significantly from 1.2% in 2011 to 18.5% in 2014 (p = 0.00001), with a concomitant decrease in the genetic variability: ST320 consistently predominated after vaccine-introduction (61.1%). Overall, our results showed a post-PCV10 increase in the frequency of serotype 19A. This was accompanied by a selection of CC320 and antimicrobial resistance.
The fraction of organic matter present affects the fragmentation behavior of sialoliths; thus, pretherapeutic information on the degree of mineralization is relevant for a correct selection of lithotripsy procedures. This work proposes a methodology for in vivo characterization of salivary calculi in the pretherapeutic context. Sialoliths were characterized in detail by X-ray computed microtomography (μCT) in combination with atomic emission spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. Correlative analysis of the same specimens was performed by in vivo and ex vivo helical computed tomography (HCT) and ex vivo μCT. The mineral matter in the sialoliths consisted essentially of apatite (89 vol%) and whitlockite (11 vol%) with average density of 1.8 g/cm3. In hydrated conditions, the mineral mass prevailed with 53 ± 13 wt%, whereas the organic matter, with a density of 1.2 g/cm3, occupied 65 ± 10% of the sialoliths’ volume. A quantitative relation between sialoliths mineral density and X-ray attenuation is proposed for both HCT and μCT.
Important Bird and Biodiversity Areas (IBAs) are sites identified as being globally important for the conservation of bird populations on the basis of an internationally agreed set of criteria. We present the first review of the development and spread of the IBA concept since it was launched by BirdLife International (then ICBP) in 1979 and examine some of the characteristics of the resulting inventory. Over 13,000 global and regional IBAs have so far been identified and documented in terrestrial, freshwater and marine ecosystems in almost all of the world’s countries and territories, making this the largest global network of sites of significance for biodiversity. IBAs have been identified using standardised, data-driven criteria that have been developed and applied at global and regional levels. These criteria capture multiple dimensions of a site’s significance for avian biodiversity and relate to populations of globally threatened species (68.6% of the 10,746 IBAs that meet global criteria), restricted-range species (25.4%), biome-restricted species (27.5%) and congregatory species (50.3%); many global IBAs (52.7%) trigger two or more of these criteria. IBAs range in size from < 1 km2 to over 300,000 km2 and have an approximately log-normal size distribution (median = 125.0 km2, mean = 1,202.6 km2). They cover approximately 6.7% of the terrestrial, 1.6% of the marine and 3.1% of the total surface area of the Earth. The launch in 2016 of the KBA Global Standard, which aims to identify, document and conserve sites that contribute to the global persistence of wider biodiversity, and whose criteria for site identification build on those developed for IBAs, is a logical evolution of the IBA concept. The role of IBAs in conservation planning, policy and practice is reviewed elsewhere. Future technical priorities for the IBA initiative include completion of the global inventory, particularly in the marine environment, keeping the dataset up to date, and improving the systematic monitoring of these sites.
Eight new species of Pyrenulaceae are described as new to science from Brazil, Guyana and Puerto Rico. Pyrenula sanguineomeandrata Aptroot & Mercado Diaz (with a thallus with red, KOH+ purple pigmentation of lines or a reticulum, simple ascomata with vertical ostioles, a deep red inspersed, KOH+ orange hamathecium, and dark brown 3-septate ascospores 25–29×10–12 μm) and P. sanguineostiolata Aptroot & Mercado Diaz (with a thallus with deeply immersed simple ascomata with vertical ostioles, which are superficial and bright red, and 3-septate ascospores 25–28×9–12 μm) are described from submontane evergreen forests in Puerto Rico. Pyrenula biseptata Aptroot & M. Cáceres (with simple ascomata with vertical ostioles, an inspersed hamathecium and 2-septate ascospores 11–12×4·5–5·0 μm) and P. xanthinspersa Aptroot & M. Cáceres (with an ecorticate thallus containing lichexanthone, simple ascomata with vertical ostioles, not inspersed hamathecium and 3-septate ascospores 14–17×6·0–7·5 μm) are described from rainforest in Amazonian Brazil. Pyrenula subvariabilis Aptroot & Sipman (with fused ascomata with lateral ostioles and submuriform ascospores 17–20(–25)×6–9 μm) and Sulcopyrenula biseriata Aptroot & Sipman (with a thallus containing lichexanthone, simple ascomata with lateral ostioles and lozenge-shaped ascospores with 8 locules, (13–)15–17(–20)×8–10 (width)×6–7 (thickness) μm) are described from savannahs in Guyana. Special attention is paid to the genus Pyrgillus: two new species from the 3-septate core group of this small genus are described from Brazil, viz. P. aurantiacus Aptroot & M. Cáceres (with a corticate thallus containing lichexanthone, mazaedium with orange, KOH+ violet, UV+ red pruina and ascospores of 13–16×6·0–7·5 μm) and P. rufus Aptroot & M. Cáceres (with a corticate thallus containing lichexanthone, mazaedium with dark red, KOH+ orange, UV+ red pruina and ascospores of 15·0–17·5×5·0–6·5 μm). An updated key to the 3-septate species of Pyrgillus is provided.
This study aimed to evaluate the risk factors for tuberculosis (TB) treatment default in a priority city for disease control in Brazil. A cohort of TB cases diagnosed from 2008 to 2009 was followed up from patients’ entry into three outpatient sites, in Juiz de Fora, Minas Gerais (Brazil), until the recording of the outcomes. Drug addiction, alcoholism and treatment site appeared to be independently associated with default. Current users of crack as the hardest drug (odds ratio (OR) 12·25, 95% confidence interval (CI) 3·04–49·26) were more likely to default than other hard drug users (OR 5·67, 95% CI 1·34–24·03), former users (OR 4·12, 95% CI 1·11–15·20) and those not known to use drugs (reference group). Consumers at high risk of alcoholism (OR 2·94, 95% CI 1·08–7·99) and those treated in an outpatient hospital unit (OR 8·22, 95% CI 2·79–24·21%) also were more likely to default. Our results establish that substance abuse was independently associated with default. National TB programmes might be more likely to achieve their control targets if they include interventions aimed at improving adherence and cure rates, by diagnosing and treating substance abuse concurrently with standard TB therapy.
In Northeast of Portugal sheep is reared under extensive systems. These systems frequently involve expressive body composition changes due to the storing and mobilization of body reserves, mainly fat. Body condition score (BCS) is the most common way to assess these reserves and the nutritional status of ewes. However due to the subjective nature of BCS, their quality has been questioned and other alternatives has been studied. For cattle there are some studies that use the real time ultrasonography (RTU) to evaluate the BCS (Schwager-Suter et al., 2000; Broring et al., 2003), but this approach was not tested in ewes. Therefore the aim of the present study was to establish a relationship between the BCS and ultrasound subcutaneous fat (SF) and Longissimus thoracis et lumborum muscle (LM) measurements.
It is a general believe that the local sheep breed Churra da Terra Quente (CTQ), reared in the Northeast of Portugal is well adapted to the conditions of its production system. However, there are large gaps on our knowledge to allow understanding of such claimed adaptation. Several researchers have found differences in digestibility between sheep breeds (e.g. Givens and Moss, 1994; López et al., 2001), suggesting that those fed natural resources can have an improved ability to digest fibre. This experiment was designed to compare digestibility coefficients of a high– and a low–roughage diet measured on sheep from CTQ and Ile-de-France (IF) breeds at the same degree of maturity.
Phosphorus and calcium deficiency in horses represents an important factor responsible for the low equine production in Brazil. The basic mechanisms of P and Ca metabolism differ substantially among species. Regulation of P and Ca metabolism is less well understood in horses than in others species. With the use of the isotopic dilution technique is possible to evaluate the metabolism for this mineral. The aim of the present experiment was to study the effect of different Ca levels in the diet on P and Ca metabolism in horses.
With the use of radioactive calcium (Ca) it is possible to study the kinetic aspects of Ca metabolism. Research in Brazil has been carried out to study mineral metabolism in sheep and cattle, especially phosphorus, by using isotope dilution techniques. However, there is very little information on Ca metabolism in sheep. The objective of this experiment was to study the effects of various Ca sources on the Ca metabolism in sheep by using isotope and balance techniques.
Two separate experiments were conducted in 2015 and 2016 in Citra, FL to investigate the effects of preplant application timing of 2,4-D and dicamba on sesame stand and yield. Nonlinear regression analysis was performed to determine the application timing that caused 10% stand or yield reduction (GR10) compared to the nontreated control (NTC) and expressed as d before planting (DBP; longer intervals indicate more injury). Likewise, regression analysis was used to determine sesame stand that resulted in 10% yield reduction (YR10) expressed as plants m−1 row. Stand measured 3 wk after planting (WAP) revealed 2,4-D applied at 0.53 kg ae ha−1 to be the least injurious treatment to sesame stand (GR10=6.4 DBP). Conversely, dicamba at 1.12 kg ha−1 produced a GR10 of 15.7 DBP for sesame stand at 3 WAP. 2,4-D applied at 0.53 and 1.06 kg ha−1 and dicamba applied at 0.56 kg ha−1 had the lowest GR10 for yield of 2, 3.7, and 3 DBP, respectively. Dicamba applied at 1.12 kg ha−1 proved to be the most injurious treatment to yield, which produced a GR10 value of 10.3 DBP. To simulate possible stand losses associated with dicamba or 2,4-D and the subsequent effect on yield, a separate experiment was conducted in which sesame was thinned to various plant densities and yield was recorded to determine the relationship between plant stand and seed yield. The regression analysis of these data was then compared to that of the experiment treated with 2,4-D and dicamba to separate any physiological effects of the herbicides that would lead to yield reduction from yield effects due to stand loss only. Rate constants were compared and no statistical differences were detected between herbicide and non-herbicide treatments, suggesting that yield reductions that occur from preplant applications of 2,4-D and dicamba were purely due to stand reductions.
Lithotripsy methods show relatively low efficiency in the fragmentation of sialoliths compared with the success rates achieved in the destruction of renal calculi. However, the information available on the mechanical behavior of sialoliths is limited and their apparently tougher response is not fully understood. This work evaluates the hardness and Young’s modulus of sialoliths at different scales and analyzes specific damage patterns induced in these calcified structures by ultrasonic vibrations, pneumoballistic impacts, shock waves, and laser ablation. A clear correlation between local mechanical properties and ultrastructure/chemistry has been established: sialoliths are composite materials consisting of hard and soft components of mineralized and organic nature, respectively. Ultrasonic and pneumoballistic reverberations damage preferentially highly mineralized regions, leaving relatively unaffected the surrounding organic matter. In contrast, shock waves leach the organic component and lead to erosion of the overall structure. Laser ablation destroys homogeneously the irradiated zones regardless of the mineralized/organic nature of the underlying ultrastructure; however, damage is less extensive than with mechanical methods. Overall, the present results show that composition and internal structure are key features behind sialoliths’ comminution behavior and that the organic matter contributes to reduce the therapeutic efficiency of lithotripsy methods.
The aim of this study was to evaluate the effect of dietary lysine on performance, protein deposition and respiratory chain gene expression in male broilers. A total of 252 Cobb 500 broilers were distributed, in a completely randomized design, into four treatments with seven replicates of nine birds per experimental unit. Experimental treatments consisted of diets based on corn and soybean meal, with four levels of digestible lysine: 1.016%, 1.099%, 1.182% and 1.265%. The increase in the level of digestible lysine in the diet provided higher weight gains, feed efficiency and body protein deposition. Birds fed the lowest level of dietary lysine (1.016%) showed a lower expression of genes such as NADH dehydrogenase subunit I (ND1), cytochrome b (CYTB) and cytochrome c oxidase subunits I (COX I), II (COX II) and III (COX III), displaying the worst performance and body protein deposition. This demonstrates the relationship existing between the expression of the evaluated genes and the performance responses. In conclusion, results indicate that broilers fed diets with higher levels of digestible lysine have increased messenger RNA expression of some genes coded in the mitochondrial electron transport chain (ND1, CYTB, COX I, COX II and COX III). It may be stated that diets with proper levels of digestible lysine, within the ‘ideal protein’ concept, promote the expression of genes, which increases the mitochondrial energy, thereby fostering body protein deposition and the performance of broilers in the starter phase.
Cysticercosis, a leading cause of acquired epilepsy in developing countries, has been controlled or eradicated in industrialized countries. This paradigm has recently been challenged, with human neurocysticercosis (NCC) being increasingly diagnosed in these countries. In order to assess the NCC burden in Portugal, a retrospective study on NCC hospitalizations (2006–2013) was conducted based on the national database on hospital morbidity: 357 hospitalized cases were detected. NCC was most frequent in the following age groups: 20–64 years (n = 197, 55·2%) >64 years (n = 111, 31·1%), and <20 years (n = 49, 13·7%). In the Norte and Centro regions cases tended to be older than in the Lisboa and Vale do Tejo Region. The results raise concerns for imported and autochthonous disease, suggesting the Lisboa and Vale do Tejo Region, due to its higher frequency of cases at younger ages, as a priority for research and intervention, and further suggest that NCC should be under surveillance (notifiable). The National Observatory of Cysticercosis and Taeniasis has been established and will define NCC cases as well as monitoring and surveillance.
Objective: To investigate the occurrence of early-onset neonatal sepsis (EOS) in twin–twin transfusion syndrome (TTTS) managed with laser surgery.
Study design: We performed a prospective cohort study of all consecutive TTTS cases treated with laser surgery (TTTS group) delivered at the Leiden University Medical Center. We recorded the occurrence of EOS, defined as a positive blood culture ≤72 hours postpartum (proven sepsis) or administration of a full course of antibiotics due to risk factors or signs of sepsis, in the absence of a positive blood culture (suspected sepsis). Perinatal variables in the TTTS group were compared with uncomplicated monochorionic twins (no-TTTS group). A multivariate model was generated, examining the association between EOS and gestational age at birth, interval between laser surgery and birth, anterior placenta, laser period (first study period: 2002–2008; second study period: 2009–2015), and preterm premature rupture of membranes (PPROM).
Results: The rates of combined suspected and proven EOS in the TTTS group and no-TTTS group were 16% (68/416) and 10% (55/542), respectively (relative ratio [RR] 1.74, 95% confidence interval [CI] 1.19–2.55). Multivariate analysis showed that EOS in the TTTS group was independently associated with lower gestational age at birth (odds ratio [OR] 0.75, 95% CI 0.63–0.88), first study period (OR 2.25, 95% CI 1.08–4.67) and PPROM (OR 2.47, 95% CI 1.28–4.75).
Conclusion: The rate of EOS in the TTTS group is low, but increased compared to the no-TTTS group. EOS in TTTS is independently associated with premature delivery, earlier laser period, and PPROM.
The benefits of fetoscopic laser photocoagulation (FLP) for treatment of twin-to-twin transfusion syndrome (TTTS) have been recognized for over a decade, yet access to FLP remains limited in many settings. This means at a population level, the potential benefits of FLP for TTTS are far from being fully realized. In part, this is because there are many centers where the case volume is relatively low. This creates an inevitable tension; on one hand, wanting FLP to be readily accessible to all women who may need it, yet on the other, needing to ensure that a high degree of procedural competence is maintained. Some of the solutions to these apparently competing priorities may be found in novel training solutions to achieve, and maintain, procedural proficiency, and with the increased utilization of ‘competence based’ assessment and credentialing frameworks. We suggest an under-utilized approach is the development of collaborative surgical services, where pooling of personnel and resources can improve timely access to surgery, improve standardized assessment and management of TTTS, minimize the impact of the surgical learning curve, and facilitate audit, education, and research. When deciding which centers should offer laser for TTTS and how we decide, we propose some solutions from a collaborative model.
Fetoscopic surgery is widely accepted as the preferred first-line treatment for twin–twin transfusion syndrome (TTTS). Nonetheless, the broad diffusion of this technique relies on a single multicentric-randomized trial. We hereby question this trial in a post-hoc Bayesian analysis, submitting its results to several scenarios comprising the alternative published non-randomized literature and pessimistic opinions regarding this surgery. Furthermore, we also discuss further refinements in indications, questioning potential alternatives in early stages of the disease.
Monochorionic twins share a single placenta and are connected with each other through vascular anastomoses. Unbalanced inter-twin blood transfusion may lead to various complications, including twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS). TAPS was first described less than a decade ago, and the pathogenesis of TAPS results from slow blood transfusion from donor to recipient through a few minuscule vascular anastomoses. This gradually leads to anemia in the donor and polycythemia in the recipient, in the absence of twin oligo-polyhydramnios sequence (TOPS). TAPS may occur spontaneously in 3–5% of monochorionic twins or after laser surgery for TTTS. The prevalence of post-laser TAPS varies from 2% to 16% of TTTS cases, depending on the rate of residual anastomoses. Pre-natal diagnosis of TAPS is currently based on discordant measurements of the middle cerebral artery peak systolic velocity (MCA-PSV; >1.5 multiples of the median [MoM] in donors and <1.0 in recipients). Post-natal diagnosis is based on large inter-twin hemoglobin (Hb) difference (>8 g/dL), and at least one of the following: reticulocyte count ratio >1.7 or minuscule placental anastomoses. Management includes expectant management, and intra-uterine blood transfusion (IUT) with or without partial exchange transfusion (PET) or fetoscopic laser surgery. Post-laser TAPS can be prevented by using the Solomon laser surgery technique. Short-term neonatal outcome ranges from isolated inter-twin Hb differences to severe neonatal morbidity and neonatal death. Long-term neonatal outcome in post-laser TAPS is comparable with long-term outcome after treated TTTS. This review summarizes the current knowledge after 10 years of research on the pathogenesis, diagnosis, management, and outcome in TAPS.