•Core biopsy samples with the powered drill offer higher diagnostic accuracy.•Core biopsy specimens demonstrate less crush artifact and fragmentation.•The more expensive powered drill is cost ...effective compared to manual needle kits.
Bone biopsies are traditionally performed using manual drill devices. More recently, powered drill biopsy systems have been developed, ostensibly to improve diagnostic yield. We compare the powered drill biopsy system to traditional manual needle devices on the basis of diagnostic yield, specimen size and material costs. 309 consecutive bone biopsy procedures performed with imaging guidance from a single academic institution were retrospectively reviewed. Specimen diagnostic adequacy, qualitative interpretation of diagnostically inadequate specimens, aggregate specimen volume and material costs were assessed. Econometric analysis was performed to assess the relationship between materials cost and diagnostic yield. Diagnostic yield and average core specimen volume were significantly higher in the powered drill group, with 86% of cases yielding adequate biopsy specimens versus 67% of cases using the manual method. The materials cost associated with the powered drill device was higher than those of any of the manual needle devices with an average difference of $270.19 per case, however, this was offset due to higher diagnostic yield suggesting that the increased diagnostic accuracy achieved by the powered drill does not carry a significant added financial burden. The powered drill bone biopsy system results in a significantly higher yield of diagnostically adequate biopsy specimens compared to traditional manual needles, possibly attributed to larger and more intact obtained core specimen volumes and is more economically viable off-setting the higher cost.
The major histocompatibility complex (MHC) is a dynamic genome region with an essential role in the adaptive immunity of vertebrates, especially antigen presentation. The MHC is generally divided ...into subregions (classes I, II and III) containing genes of similar function across species, but with different gene number and organisation. Crocodylia (crocodilians) are widely distributed and represent an evolutionary distinct group among higher vertebrates, but the genomic organisation of MHC within this lineage has been largely unexplored. Here, we studied the MHC region of the saltwater crocodile (Crocodylus porosus) and compared it with that of other taxa. We characterised genomic clusters encompassing MHC class I and class II genes in the saltwater crocodile based on sequencing of bacterial artificial chromosomes. Six gene clusters spanning ∼452 kb were identified to contain nine MHC class I genes, six MHC class II genes, three TAP genes, and a TRIM gene. These MHC class I and class II genes were in separate scaffold regions and were greater in length (2-6 times longer) than their counterparts in well-studied fowl B loci, suggesting that the compaction of avian MHC occurred after the crocodilian-avian split. Comparative analyses between the saltwater crocodile MHC and that from the alligator and gharial showed large syntenic areas (>80% identity) with similar gene order. Comparisons with other vertebrates showed that the saltwater crocodile had MHC class I genes located along with TAP, consistent with birds studied. Linkage between MHC class I and TRIM39 observed in the saltwater crocodile resembled MHC in eutherians compared, but absent in avian MHC, suggesting that the saltwater crocodile MHC appears to have gene organisation intermediate between these two lineages. These observations suggest that the structure of the saltwater crocodile MHC, and other crocodilians, can help determine the MHC that was present in the ancestors of archosaurs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summer annual grass‐legume mixtures may provide supplemental grazing for livestock when cool‐season pastures are less productive, but nitrogen fertilizer recommendations for these mixtures are not ...well established. Inputs to these systems are often high, so optimizing N fertilizer rates may increase appeal to producers. This study evaluated the effects of increasing botanical diversity and N fertilizer application on the yield and botanical composition of summer annual mixtures in four environments in Kentucky. Nitrogen fertilizer rates of 0, 56, 112, 168, and 224 kg N ha–1 were applied to a sudangrass Sorghum bicolor (L.) Moench × Sorghum sudanese (P.) Stapf monoculture, a three‐species mixture, and an 11‐species mixture. In three out of four environments, sward biomass increased as N application increased (average of 15 kg dry matter (DM) ha–1 increase per kg N ha–1; p < .05). Mixture complexity had no effect on forage DM accumulation in three out of four environments (4,000, 5,830, and 7,280 kg DM ha–1 averaged over mixture for three environments; p > .05). Mixtures were overwhelmingly dominated by grasses, resulting in low functional diversity. Legumes did not respond to N (p > .05), but their contribution to sward DM was <4%. Species compatibility should be a priority when utilizing multi‐species mixtures. If a stronger legume component is desired, care must be taken to provide management that favors these species, such as reduced grass‐seeding rates to limit competition, especially during initial establishment.
Core Ideas
224 kg N ha–1 increased yield by 1.9 times over no N in three out of four environments.
Mixtures did not outyield monocultures and were dominated by high‐yielding species.
Legumes are not competitive when planted with high seeding rates of summer annual grasses.
Annual pastures should utilize compatible species to reduce competitive dominance.
Abstract The duration of pregnancy varies between 40+0 and 41+3 weeks. Conventionally, and essentially arbitrarily, a pregnancy is considered to be “prolonged” after 41+0 weeks, but the infant is not ...considered “post-term” until 42+0 weeks (Professional consensus). A term birth thus occurs during the period from 37+0 to 41+6 weeks. In France, prolonged pregnancies (≥41+0 weeks) involve 15–20% of pregnant women, and post-term pregnancies (≥42+0 weeks) approximately 1%. The frequency of post-term pregnancies is very heterogeneous: in Europe and the United States, it ranges from 0.5% to 10% according to country. In prolonged pregnancies, the cesarean section rate—especially the emergency cesarean rate—is multiplied by approximately 1.5 (grade B). From 370–6 to 430–6 weeks, the risk of perinatal mortality increases regularly, from 0.7‰ to 5.8‰. Meconium aspiration syndrome is responsible for substantial morbidity and mortality, and its incidence increases regularly between 38+0 and 42+6 weeks, from 0.24‰ to 1.42‰ (grade B). Similarly, the risks of neonatal acidosis (grade B), 5-min Apgar scores less than 7 (grade B) and admissions to neonatal intensive care (grade B) increase progressively between 38+0 and 42+6 weeks. These risks appear to double for post-term growth-restricted newborns (grade C). Ultrasound dating of the pregnancy makes it possible to reduce the risk that it will be incorrectly considered prolonged and that labor will therefore be induced unnecessarily. To harmonize practices, if the crown-rump length (CRL) is correctly measured (this measurement should be taken between 11+0 and 13+6 weeks, when CRL should measure from 45 to 84 mm), ultrasound dating based on it should be used to determine the official date pregnancy began, regardless of its difference from the date assumed by the patient or estimated based on the date of the last menstrual period. This rule does not apply to pregnancies by IVF, for which the date pregnancy began is defined by the date of oocyte retrieval (Professional consensus). From 370–6 to 430–6 weeks, the risk of perinatal mortality increases regularly and there is no threshold at which a clear increase in perinatal mortality becomes visible. Fetal monitoring by cardiotocography (CTG) that begins at 41+0 weeks would cover approximately 20% of women and reduce perinatal morbidity compared with monitoring that begins at 42+0 weeks (grade C). The frequency recommended for this monitoring ranges between two and three times a week (Professional consensus). For ultrasonography assessment, measurement of the largest fluid pocket is recommended, because measurement of the amniotic fluid index (that is, the sum of the four quadrants) is accompanied by more diagnoses of oligohydramnios, inductions of labor, and cesareans for fetal distress without any improvement in neonatal prognosis (grade A). The practice of assessing the Manning biophysical score increases the number of diagnoses of oligohydramnios and fetal heart rage (FHR) abnormalities and generates an increase in the rates of inductions and cesareans without improving neonatal prognosis. The use of this biophysical score in monitoring prolonged pregnancies is therefore not recommended (grade B). In the absence of a specific disorder, induction of labor can be proposed in patients between 41+0 and 42+6 weeks (grade B). Nonetheless, the choice of prolongation beyond above 42+0 weeks appears to involve an increase in fetal risk, which must be explained to the patient and balanced against the potential disadvantages of induction (Professional consensus). Stripping the membranes can reduce the duration of pregnancy by increasing the number of patients going into labor spontaneously during the week afterward (grade B). Compared to an expectant approach, it does not increase the cesarean section rate (grade A). It reduces recourse to induction by 41% at 41+0 weeks and by 72% at 42+0 weeks (grade B), without increasing the risk of either membrane rupture or maternal or neonatal infection (grade B). Used as a tampon or vaginal gel, prostaglandins E2 (PGE2) are an effective method of inducing labor (grade A). They can be used to induce labor successfully, regardless of cervical ripeness (grade A). If misoprostol is chosen, the lowest dose is to be preferred, starting with a vaginal dose of 25 μg every 3–6 h (grade A). For misoprostol, more powerful studies remain necessary for better defining the doses, routes of administration, tolerance and indications. Misoprostol at any dose is contraindicated in women with uterine scars (grade B). Placement of an intracervical Foley catheter is an effective mechanical means of inducing labor, with less uterine hyperstimulation than prostaglandins and no increase in the cesarean section rate (grade A). Nonetheless, as the risk of infection might be increased, this technique requires more robust evaluation before entering general practice (grade B). In cases of meconium-stained amniotic fluid, pharyngeal aspiration before delivery of the shoulders is not recommended (grade A). The team managing a post-term newborn with meconium-stained amniotic fluid at birth must know how to perform intubation and, if the intubation is not helpful, endotracheal aspiration (grade C) and ventilation with a mask. Routine endotracheal intubation of a vigorous newborn is not recommended (grade A).
PARP Inhibitors in Ovarian Cancer. Reply González-Martín, Antonio; Monk, Bradley J
The New England journal of medicine,
04/2020, Letnik:
382, Številka:
16
Journal Article
To determine if inhibition of inducible nitric oxide synthase (iNOS) with cindunistat hydrochloride maleate slows progression of osteoarthritis (OA) METHODS: This 2-year, multinational, double-blind, ...placebo-controlled trial enrolled patients with symptomatic knee OA (Kellgren and Lawrence Grade (KLG) 2 or 3). Standard OA therapies were permitted throughout. Patients were randomly assigned to cindunistat (50 or 200 mg/day) or placebo. Randomisation was stratified by KLG. Radiographs to assess joint space narrowing (JSN) were acquired using the modified Lyon-schuss protocol at baseline, week 48 and 96.
Of 1457 patients (50 mg/day, n=485; 200 mg/day, n=486; placebo, n=486), 1048 (71.9%) completed the study. Patients were predominantly women; 56% had KLG3. The primary analysis did not demonstrate superiority of cindunistat versus placebo for rate of change in JSN. In KLG2 patients, JSN after 48 weeks was lower with cindunistat 50 mg/day versus placebo (p=0.032). Least-squares mean±SE JSN with cindunistat 50 mg/day ( -0.048±0.028 mm) and 200 mg/day (-0.062±0.028 mm) were 59.9% (95% CI 6.8% to 106.9%) and 48.7% (95% CI -8.4% to 93.9%) of placebo, improvement was not maintained at 96 weeks. No improvement was observed for KLG3 patients at either time-point. Cindunistat did not improve joint pain or function, but was generally well tolerated.
Cindunistat (50 or 200 mg/day) did not slow the rate of JSN versus placebo. After 48-weeks, KLG2 patients showed less JSN; however, the improvement was not sustained at 96-weeks. iNOS inhibition did not slow OA progression in KLG3 patients. CLINICAL TRIAL LISTING: NCT00565812.
The adoptive transfer of neoantigen-reactive tumor-infiltrating lymphocytes (TILs) can result in tumor regression in patients with metastatic cancer. To improve the efficacy of adoptive T cell ...therapy targeting these tumor-specific mutations, we have proposed a new therapeutic strategy, which involves the genetic modification of autologous T cells with neoantigen-specific T cell receptors (TCRs) and the transfer of these modified T cells back to cancer patients. However, the current techniques to isolate neoantigen-specific TCRs are labor intensive, time consuming, and technically challenging, not suitable for clinical applications. To facilitate this process, a new approach was developed, which included the co-culture of TILs with tandem minigene (TMG)-transfected or peptide-pulsed autologous antigen-presenting cells (APCs) and the single-cell RNA sequencing (RNA-seq) analysis of T cells to identify paired TCR sequences associated with cells expressing high levels of interferon-γ (IFN-γ) and interleukin-2 (IL-2). Following this new approach, multiple TCRs were identified, synthesized, cloned into a retroviral vector, and then transduced into donor T cells. These transduced T cells were shown to specifically recognize the neoantigens presented by autologous APCs. In conclusion, this approach provides an efficient procedure to isolate neoantigen-specific TCRs for clinical applications, as well as for basic and translational research.
The identification of antigen-specific T cell receptors (TCRs) is a complicated process, which is technically challenging and not suitable for clinical applications. To simplify this process, Lu and colleagues developed an efficient single-cell approach, which can significantly reduce the labor and time for the TCR isolation.
Patients entering treatment for alcohol problems do not have uniform treatment goals, and a pretreatment drinking goal has a significant impact on treatment outcome. The objective of this study was ...to understand better how an array of individual characteristics, including factors that affect treatment, are related to treatment goals before beginning alcohol treatment in the COMBINE (Combining Medications and Behavioral Interventions) Study.
Participants were alcohol-dependent individuals (N = 1,156; 357 women) recruited at 11 outpatient academic alcoholism-treatment clinics across the United States to participate in a randomized, double-blind, placebo-controlled trial that combined behavioral intervention with acamprosate and/or naltrexone. Treatment goal was coded as controlled drinking, conditional abstinence, or total abstinence. Multinomial logistic regressions assessed whether there were significant relationships between predictor variables and pretreatment goal selection.
Lower levels of alcohol-related consequences, lower readiness to change, higher family income, more daily drinkers in social network, and lack of prior treatment or Alcoholics Anonymous engagement predicted choice of a controlled drinking goal over a total abstinence goal. Fewer alcohol-related consequences, lower readiness to change, and more daily drinkers in-network predicted choice of a conditional abstinence goal over a total abstinence goal.
Higher levels of functioning, lower levels of consequences, no prior involvement in treatment and Alcoholics Anonymous, and a more drinking-saturated social environment are associated with the choice of a non-abstinence goal.
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