Prevention of arthritis by interleukin 10-producing B cells

In this study we have shown that activation of arthritogenic splenocytes with antigen and agonistic anti-CD40 gives raise to a B cell population that produce high levels of interleukin (IL)-10 and low levels of interferon (IFN)-{gamma}. Transfer of these B cells into DBA/1-TcR-ß-Tg mice, immunized with bovine collagen (CII) emulsified in complete Freund's adjuvant inhibited T helper type 1 differentiation, prevented arthritis development, and was also effective in ameliorating established disease. IL-10 is essential for the regulatory function of this subset of B cells, as the B cells population isolated from IL-10 knockout mice failed to mediate this protective function. Furthermore, B cells isolated from arthritogenic splenocytes treated in vitro with anti–IL-10/anti–IL-10R were unable to protect recipient mice from developing arthritis. Our results suggest a new role of a subset of B cells in controlling T cell differentiation and autoimmune disorders

Estimation of Export Supply Function for Citrus Fruit in Pakistan

There is strong evidence in the literature that export and economic growth have a positive relationship. In Pakistan, with an agrarian economy, earnings from primary agricultural exports are vital for the overall growth process. Fruits are the traditional export commodities, which contribute more than half of total export earnings from primary agricultural commodities. The persistent instability in world market prices for primary commodities has depressed the export earnings from these commodities over time. This poses great challenges to a country like Pakistan. The present study aims at examining changes in the volume of export of citrus fruit from Pakistan caused by such factors as changes in domestic and export prices, national product, foreign exchange rate, etc. The study uses time series data for the period 1975–2004 for citrus exports and related domestic price, export price, GDP, and foreign exchange rate, employing the co-integration and error correction techniques for analysis purposes.

Estimation of Export Supply Function for Citrus Fruit in Pakistan

Nature has blessed Pakistan with an ideal climate for growing a wide range of delicious fruits. Thus a very wide range of tropical, sub-tropical and temperate fruits are grown in the country. Over the years, Pakistani experts have developed unique strains of exotic fruit varieties. Pakistan is producing a large variety of fruits on an area of 734.6 thousand hectares with a total production of 5712.4 thousand tons. Out of this 354.4 thousand tons fruit is exported from the country [Pakistan (2004)]. Horticulture is an important sub-sector of agriculture and plays a vital role not only in rejuvenation of rural economy but also in improving human nutrition which is often deficient in ingredients such as vitamins and minerals. Citrus and mango are the main fruit crops which contribute substantially to the national income

Patient-Reported Outcomes following Single- and Multiple-Radius Total Knee Replacement: A Randomized, Controlled Trial

Although single-radius (SR) designs of total knee replacement (TKR) have theoretical benefits, the clinical advantage conferred by such designs is unknown. The aim of this randomized, controlled study was to compare the short-term clinical outcomes of the two design rationales. A total of 105 knees were randomized to receive either a single radius (Scorpio, Stryker; SR Group) or multiple radius (AGC, Zimmer Biomet; MR group) TKR. Patient-reported outcomes (Oxford Knee Score [OKS] and Knee Society Score [KSS]) were collected at 6 weeks, 6 months, and 1 year following surgery. No knees were revised. There was no difference in primary outcomes: OKS was 39.5 (95% confidence interval [CI]: 36.9–42.1) in the SR group and 38.1 (95% CI: 36.0–40.3) in the MR group (p = 0.40). KSS was 168.4 (95% CI: 159.8–177.0) in the SR group; 159.5 (95% CI 150.5–168.5) in the MR group (p = 0.16). There was a small but statistically significant difference in the degree of change of the objective subscale of the KSS, favoring the SR design (p = 0.04), but this is of uncertain clinical relevance. The reported benefits of SR designs do not provide demonstrable functional advantages in the short term

Mental practice with interactive 3D visual aids enhances surgical performance

Background: Evidence suggests that Mental Practice (MP) could be used to finesse surgical skills. However, MP is cognitively demanding and may be dependent on the ability of individuals to produce mental images. In this study, we hypothesised that the provision of interactive 3D visual aids during MP could facilitate surgical skill performance. Methods: 20 surgical trainees were case-matched to one of three different preparation methods prior to performing a simulated Laparoscopic Cholecystectomy (LC). Two intervention groups underwent a 25-minute MP session; one with interactive 3D visual aids depicting the relevant surgical anatomy (3D-MP group, n = 5) and one without (MP-Only, n = 5). A control group (n = 10) watched a didactic video of a real LC. Scores relating to technical performance and safety were recorded by a surgical simulator. Results: The Control group took longer to complete the procedure relative to the 3D&MP condition (p = .002). The number of movements was also statistically different across groups (p = .001), with the 3D&MP group making fewer movements relative to controls (p = .001). Likewise, the control group moved further in comparison to the 3D&MP condition and the MP-Only condition (p = .004). No reliable differences were observed for safety metrics. Conclusion: These data provide evidence for the potential value of MP in improving performance. Furthermore, they suggest that 3D interactive visual aids during MP could potentially enhance performance, beyond the benefits of MP alone. These findings pave the way for future RCTs on surgical preparation and performance

Optimization of the axial power shape in pressurized water reactors

Statement of responsibility on title-page reads: M.A. Malik, A. Kamal, M.J. Driscoll, and D.D. Lanning"November 1981."Originally presented as the first author's M.S. thesis, M.I.T. Dept. of Nuclear Engineering, 1981Includes bibliographical references (pages 112-114)Analytical and numerical methods have been applied to find the optimum axial power profile in a PWR with respect to uranium utilization. The preferred shape was found to have a large central region of uniform power density, with a roughly cosinusoidal.profile near the ends of the assembly. Reactivity and fissile enrichment distributions which yield the optimum profile were determined, and a 3-region design was developed which gives essentially the same power profile as the continuously varying optimum composition. State of the art computational methods, LEOPARD and PDQ-7, were used to evaluate the beginning-of-life and burnup history behavior of a series of three-zone assembly designs, all of which had a large central zone followed by a shorter region of higher enrichment, and with a still thinner blanket of depleted uranium fuel pellets at the outer periphery. It was found that if annular fuel pellets were used in the higher enrichment zone, a design ! was created which not only had the best uranium savings (2.8% more energy from the same amount of natural. uranium, compared to a conventional, uniform, unblanketed design), but also had a power shape with a lower peak-to-average power ratio (by 16.5%) than the reference case, and which held its power shape very nearly constant over life. This contrasted with the designs without part length annular fuel, which tended to burn into an end-peaked power distribution, and with blanket-only designs, which had a poorer peak-to-average power ratio than the reference udblanketed case.DOE contract no. DE-AC02-79ET340

Transgenerational effect of the endocrine disruptor vinclozolin on male spermatogenesis

The current study was designed to examine the actions of a model endocrine disruptor on embryonic testis development and male fertility. Pregnant rats (F0) that received a transient embryonic exposure to an environmental endocrine disruptor, vinclozolin, had male offspring (F1) with reduced sper-matogenic capacity. The reduced spermatogenetic capacity observed in the F1 male offspring was transmitted to the subsequent generations (F2–F4). The administration of vinclozolin, an androgen receptor antagonist, at 100 mg/kg/day from embryonic day 8–14 (E8–E14) of pregnancy to only the F0 dam resulted in a transgenera-tional phenotype in the subsequent male offspring in the F1–F4 generations. The litter size and male/female sex ratios were similar in controls and the vinclozolin generations. The average testes/body weight index of the postnatal day 60 (P60) males was not significantly different in the vinclozolin-treated generations compared to the controls. However, the testicular spermatid number, as well as the epididymal sperm number and motility, were significantly reduced in the vinclozolin generations compared to the control animals. Postnatal day 20 (P20) testis from the vinclozolin F2 generation had no morphological abnormalities, but did have an increase in spermatogenic cell apoptosis. Although the P60 testis morphology was predominantly normal, the germ cell apoptosis was significantly increased in the testes cross sections of animals from the vinclozolin generations. The increase in apoptosis was stage-specific in the testis, with tubules at stages IX–XIV having the highest increase in apoptotic germ cells. The tubules at stages I–V also had an increase in apoptotic germ cells compared to the control samples, but tubules at stages VI–VIII had no increase in apoptotic germ cells. An outcross of a vinclozolin generation male with a wild-type female demonstrated that the reduced spermatogenic cell phenotype was transmitted through the male germ line. An outcross with a vinclozolin generation female with a wild-type male had no phenotype. A similar phenotype was observed in outbred Sprague Dawley and inbred Fisher rat strains. Observations demonstrate that a transient exposure at the time of male sex determination to the antiandrogenic endocrine disruptor vinclozolin can induce an apparent epigenetic transgenerational phenotype with reduced spermatogenic capacity

PD-1/PD-L1 inhibitor activity in patients with gene-rearrangement positive non-small cell lung cancer-an IMMUNOTARGET case series.

BACKGROUND Prior IMMUNOTARGET registry data had suggested that responses to immune [anti PD(L)1] monotherapy in gene-arranged non-small cell lung cancer (NSCLC) were rare or absent, depending on the specific oncogene. METHODS IMMUNOTARGET sites reporting prior registry data or new individual cases of gene rearranged NSCLC seeming to benefit from immune monotherapy were explored in detail looking to both validate their diagnosis of a functional gene rearrangement and to look for features potentially differentiating them from other such cases associated with low response rates. RESULTS Five cases of NSCLC with a gene rearrangement with reported responses or prolonged stabilization from immune monotherapy were identified in total. All had little or no prior smoking history and had programmed death-ligand 1 (PD-L1) values ranging from zero to 100%. A confirmed rearrangement partner was reported in only 2 of the cases (CD74-ROS1 and KIF5B-RET), however in one of the other three cases [analplastic lymophoma kinase (ALK)], significant benefit from a relevant prior targeted therapy was noted, also consistent with the rearrangement status being correctly assigned. CONCLUSIONS Not all driver oncogene subtypes of NSCLC are equally responsive to immune monotherapy, however even among patients with well-validated gene rearranged NSCLC which has traditionally been considered immune hyporesponsive, objective responses can occur. Additional explorations of the features associated with and underlying the immune hypo-responsiveness of most, but not all, cases of gene-rearranged NSCLC are required

Contributory factors in surgical incidents as delineated by a confidential reporting system

Background Confidential reporting systems play a key role in capturing information about adverse surgical events. However, the value of these systems is limited if the reports that are generated are not subjected to systematic analysis. The aim of this study was to provide the first systematic analysis of data from a novel surgical confidential reporting system to delineate contributory factors in surgical incidents and document lessons that can be learned. Methods One-hundred and forty-five patient safety incidents submitted to the UK Confidential Reporting System for Surgery over a 10-year period were analysed using an adapted version of the empirically-grounded Yorkshire Contributory Factors Framework. Results The most common factors identified as contributing to reported surgical incidents were cognitive limitations (30.09%), communication failures (16.11%) and a lack of adherence to established policies and procedures (8.81%). The analysis also revealed that adverse events were only rarely related to an isolated, single factor (20.71%) – with the majority of cases involving multiple contributory factors (79.29% of all cases had more than one contributory factor). Examination of active failures – those closest in time and space to the adverse event – pointed to frequent coupling with latent, systems-related contributory factors. Conclusions Specific patterns of errors often underlie surgical adverse events and may therefore be amenable to targeted intervention, including particular forms of training. The findings in this paper confirm the view that surgical errors tend to be multi-factorial in nature, which also necessitates a multi-disciplinary and system-wide approach to bringing about improvements