Therapeutic efficacy of alpha-1 antitrypsin augmentation therapy on the loss of lung tissue: an integrated analysis of 2 randomised clinical trials using computed tomography densitometry

<p>Abstract</p> <p>Background</p> <p>Two randomised, double-blind, placebo-controlled trials have investigated the efficacy of IV alpha-1 antitrypsin (AAT) augmentation therapy on emphysema progression using CT densitometry.</p> <p>Methods</p> <p>Data from these similar trials, a 2-center Danish-Dutch study (n = 54) and the 3-center EXAcerbations and CT scan as Lung Endpoints (EXACTLE) study (n = 65), were pooled to increase the statistical power. The change in 15^thpercentile of lung density (PD15) measured by CT scan was obtained from both trials. All subjects had 1 CT scan at baseline and at least 1 CT scan after treatment. Densitometric data from 119 patients (AAT [Alfalastin^®or Prolastin^®], n = 60; placebo, n = 59) were analysed by a statistical/endpoint analysis method. To adjust for lung volume, volume correction was made by including the change in log-transformed total lung volume as a covariate in the statistical model.</p> <p>Results</p> <p>Mean follow-up was approximately 2.5 years. The mean change in lung density from baseline to last CT scan was -4.082 g/L for AAT and -6.379 g/L for placebo with a treatment difference of 2.297 (95% CI, 0.669 to 3.926; p = 0.006). The corresponding annual declines were -1.73 and -2.74 g/L/yr, respectively.</p> <p>Conclusions</p> <p>The overall results of the combined analysis of 2 separate trials of comparable design, and the only 2 controlled clinical trials completed to date, has confirmed that IV AAT augmentation therapy significantly reduces the decline in lung density and may therefore reduce the future risk of mortality in patients with AAT deficiency-related emphysema.</p> <p>Trial registration</p> <p>The EXACTLE study was registered in ClinicalTrials.gov as 'Antitrypsin (AAT) to Treat Emphysema in AAT-Deficient Patients'; ClinicalTrials.gov Identifier: NCT00263887.</p

2019 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations : summary from the basic life support; advanced life support; pediatric life support; neonatal life support; education, implementation, and teams; and first aid task forces

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

A mathematical and computational review of Hartree-Fock SCF methods in Quantum Chemistry

We present here a review of the fundamental topics of Hartree-Fock theory in Quantum Chemistry. From the molecular Hamiltonian, using and discussing the Born-Oppenheimer approximation, we arrive to the Hartree and Hartree-Fock equations for the electronic problem. Special emphasis is placed in the most relevant mathematical aspects of the theoretical derivation of the final equations, as well as in the results regarding the existence and uniqueness of their solutions. All Hartree-Fock versions with different spin restrictions are systematically extracted from the general case, thus providing a unifying framework. Then, the discretization of the one-electron orbitals space is reviewed and the Roothaan-Hall formalism introduced. This leads to a exposition of the basic underlying concepts related to the construction and selection of Gaussian basis sets, focusing in algorithmic efficiency issues. Finally, we close the review with a section in which the most relevant modern developments (specially those related to the design of linear-scaling methods) are commented and linked to the issues discussed. The whole work is intentionally introductory and rather self-contained, so that it may be useful for non experts that aim to use quantum chemical methods in interdisciplinary applications. Moreover, much material that is found scattered in the literature has been put together here to facilitate comprehension and to serve as a handy reference.Comment: 64 pages, 3 figures, tMPH2e.cls style file, doublesp, mathbbol and subeqn package

Angiotensin-converting enzyme gene and retinal arteriolar narrowing: The Funagata Study

The purpose of this study is to determine whether the angiotensin-converting enzyme (ACE) gene polymorphism is associated with retinal arteriolar narrowing, a subclinical marker of chronic hypertension. The Funagata Study examined a population-based sample of Japanese aged 35+ years; 368 participants had both retinal vessel diameter measurements and ACE insertion/deletion (ACE I/D) polymorphism analyses performed. Assessment of retinal vessel diameter and retinal vessel wall signs followed the protocols used in the Blue Mountains Eye Study. ACE gene polymorphisms D/D, I/D and I/I were present in 34 (9.2%), 170 (46.2%) and 164 (44.5%) participants, respectively, distributed in Hardy–Weinberg equilibrium. After multivariable adjustment, retinal arteriolar diameter was significantly narrower in subjects with the D/D genotype compared to subjects with I/D and I/I genotypes (mean difference −6.49 μm, 95% confidence interval (CI): −12.86 μm, −0.11 μm). Our study suggests that the ACE I/D polymorphism may be associated with subclinical structural arteriolar changes related to chronic hypertension

Emergent versus delayed lithotripsy for obstructing ureteral stones: a cumulative analysis of comparative studies

Objective To analyze the current evidence on the use of ureteroscopy (URS) and extracorporeal shock wave lithotripsy (ESWL) for the management of obstructing ureteral stones in emergent setting. Methods A systematic literature review was performed up to June 2016 using Pubmed and Ovid databases to identify pertinent studies. The PRISMA criteria were followed for article selection. Separate searches were done using a combinations of several search terms: "laser lithotripsy", "ureteroscopy", "extracorporeal shock wave lithotripsy", "ESWL", "rapid", "immediate", "early", "delayed", "late", "ureteral stones", "kidney stones", "renal stones". Only titles related to emergent/rapid/immediate/early (as viably defined in each study) versus delayed/late treatment of ureteral stones with either URS and/or ESWL were considered for screening. Demographics and operative outcomes were compared between emergent and delayed lithotripsy. RevMan review manager software was used to perform data analysis. Results Four studies comparing emergent (n = 526) versus delayed (n = 987) URS and six studies comparing emergent (n = 356) versus delayed (n = 355) SWL were included in the analysis. Emergent URS did not show any significant difference in terms of stone-free rate (91.2 versus 90.9%; OR 1.04; CI 0.71, 1.52; p = 0.84), complication rate (8.7% for emergent versus 11.5% for delayed; OR 0.94; CI 0.65, 1.36; p = 0.74) and need for auxiliary procedures (OR 0.85; CI 0.42, 1.7; p = 0.85) when compared to delayed URS. Emergent ESWL was associated with a higher likelihood of stone free status (OR 2.2; CI 1.55, 3.17; p < 0.001) and a lower likelihood of need for auxiliary maneuvers (OR 0.49; CI 0.33, 0.72; p < 0.001) than the delayed procedure. No differences in complication rates were noticed between the emergent and delayed ESWL (p = 0.37). Conclusions Emergent lithotripsy, either ureteroscopic or extracorporeal, can be offered as an effective and safe treatment for patients with symptomatic ureteral stone. If amenable to ESWL, based on stone and patient characteristics, an emergent approach should be strongly considered. Ureteroscopy in the emergent setting is mostly reserved for distally located stones. The implementation of these therapeutic approaches is likely to be dictated by their availability.info:eu-repo/semantics/publishedVersio

Variation in WNT7A is unlikely to be a cause of familial Congenital Talipes Equinovarus

<p>Abstract</p> <p>Background</p> <p>Genetic factors make an important contribution to the aetiology of congenital talipes equinovarus (CTEV), the most common developmental disorder of the lower limb. WNT7A was suggested as a candidate gene for CTEV on the basis of a genome-wide scan for linkage in a large multi-case family. WNT7A is a plausible candidate gene for CTEV as it provides a signal for pattern formation during limb development, and mutation in WNT7A has been reported in a number of limb malformation syndromes.</p> <p>Methods</p> <p>We investigated the role of WNT7A using a family-based linkage approach in our large series of European multi-case CTEV families. Three microsatellite markers were used, of which one (D3S2385) is intragenic, and the other two (D3S2403, D3S1252) are 700 kb 5' to the start and 20 kb from the 3' end of the gene, respectively. Ninety-one CTEV families, comprising 476 individuals of whom 211 were affected, were genotyped. LOD scores using recessive and incomplete-dominant inheritance models, and non-parametric linkage scores, excluded linkage.</p> <p>Results</p> <p>No significant evidence for linkage was observed using either parametric or non-parametric models. LOD scores for the parametric models remained strongly negative in the regions between the markers, and in the 0.5 cM intervals outside the marker map. No significant lod scores were obtained when the data were analysed allowing for heterogeneity.</p> <p>Conclusion</p> <p>Our evidence suggests that the WNT7A gene is unlikely to be a major contributor to the aetiology of familial CTEV.</p

Mitochondrial DNA Haplogroup Analysis Reveals no Association between the Common Genetic Lineages and Prostate Cancer in the Korean Population

Mitochondrial DNA (mtDNA) variation has recently been suggested to have an association with various cancers, including prostate cancer risk, in human populations. Since mtDNA is haploid and lacks recombination, specific mutations in the mtDNA genome associated with human diseases arise and remain in particular genetic backgrounds referred to as haplogroups. To assess the possible contribution of mtDNA haplogroup-specific mutations to the occurrence of prostate cancer, we have therefore performed a population-based study of a prostate cancer cases and corresponding controls from the Korean population. No statistically significant difference in the distribution of mtDNA haplogroup frequencies was observed between the case and control groups of Koreans. Thus, our data imply that specific mtDNA mutations/lineages did not appear to have a significant effect on a predisposition to prostate cancer in the Korean population, although larger sample sizes are necessary to validate our results

Recovering Dietary Information from Extant and Extinct Primates Using Plant Microremains

When reconstructing the diets of primates, researchers often rely on several well established methods, such as direct observation, studies of discarded plant parts, and analysis of macrobotanical remains in fecal matter. Most of these studies can be performed only on living primate groups, however, and the diets of extinct, subfossil, and fossil groups are known only from proxy methods. Plant microremains, tiny plant structures with distinctive morphologies, can record the exact plant foods that an individual consumed. They can be recovered from recently deceased and fossil primate samples, and can also be used to supplement traditional dietary analyses in living groups. Here I briefly introduce plant microremains, provide examples of how they have been successfully used to reconstruct the diets of humans and other species, and describe methods for their application in studies of primate dietary ecology

Human Remains from the Pleistocene-Holocene Transition of Southwest China Suggest a Complex Evolutionary History for East Asians

BACKGROUND: Later Pleistocene human evolution in East Asia remains poorly understood owing to a scarcity of well described, reliably classified and accurately dated fossils. Southwest China has been identified from genetic research as a hotspot of human diversity, containing ancient mtDNA and Y-DNA lineages, and has yielded a number of human remains thought to derive from Pleistocene deposits. We have prepared, reconstructed, described and dated a new partial skull from a consolidated sediment block collected in 1979 from the site of Longlin Cave (Guangxi Province). We also undertook new excavations at Maludong (Yunnan Province) to clarify the stratigraphy and dating of a large sample of mostly undescribed human remains from the site. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a detailed comparison of cranial, including a virtual endocast for the Maludong calotte, mandibular and dental remains from these two localities. Both samples probably derive from the same population, exhibiting an unusual mixture of modern human traits, characters probably plesiomorphic for later Homo, and some unusual features. We dated charcoal with AMS radiocarbon dating and speleothem with the Uranium-series technique and the results show both samples to be from the Pleistocene-Holocene transition: ∼14.3-11.5 ka. CONCLUSIONS/SIGNIFICANCE: Our analysis suggests two plausible explanations for the morphology sampled at Longlin Cave and Maludong. First, it may represent a late-surviving archaic population, perhaps paralleling the situation seen in North Africa as indicated by remains from Dar-es-Soltane and Temara, and maybe also in southern China at Zhirendong. Alternatively, East Asia may have been colonised during multiple waves during the Pleistocene, with the Longlin-Maludong morphology possibly reflecting deep population substructure in Africa prior to modern humans dispersing into Eurasia

Effects of Mowing on Methane Uptake in a Semiarid Grassland in Northern China

Background: Mowing is a widely adopted management practice for the semiarid steppe in China and affects CH4 exchange. However, the magnitude and the underlying mechanisms for CH 4 uptake in response to mowing remain uncertain. Methodology/Principal Findings: In two consecutive growing seasons, we measured the effect of mowing on CH 4 uptake in a steppe community. Vegetation was mowed to 2 cm (M2), 5 cm (M5), 10 cm (M10), 15 cm (M15) above soil surface, respectively, and control was set as non-mowing (NM). Compared with control, CH4 uptake was substantially enhanced at almost all the mowing treatments except for M15 plots of 2009. CH4 uptake was significantly correlated with soil microbial biomass carbon, microbial biomass nitrogen, and soil moisture. Mowing affects CH 4 uptake primarily through its effect on some biotic factors, such as net primary productivity, soil microbial C\N supply and soil microbial activities, while soil temperature and moisture were less important. Conclusions/Significance: This study found that mowing affects the fluxes of CH4 in the semiarid temperate steppe of north China