Miracle-dz/UniFAR-FTUs huggingface dataset:
Variation in the Incidence and Magnitude of Tumor-Infiltrating Lymphocytes in Breast Cancer Subtypes: A Systematic Review.

Importance The presence of tumor-infiltrating lymphocytes (TILs) is a favorable prognostic factor in breast cancer, and TILs may synergize with chemotherapy and immune checkpoint inhibitor therapy for improved clinical response. A more detailed understanding of the variation in lymphocytic infiltration in breast cancer may aid in identifying subtypes more amenable to immunomodulation. Objective To determine the median percentage of patients with breast cancer with no, intermediate, or high levels of TIL and assess variations in lymphocytic cell subsets across breast cancer subtypes. Evidence Review Eligible studies (PubMed, 1990-2015) analyzed tumor lymphocytic, CD8+, and FOXP3+ cellular infiltrates, and used multivariable analyses and quantitative methods for enumerating cell populations. Selection of of studies was performed in accordance with PRISMA guidelines and evaluated by 2 independent appraisers. Findings Fifteen studies (n = 13 914) met prespecified criteria and were reviewed in December 2015. A median of 11% (range, 5%-26%) of breast cancers demonstrate lymphocyte-predominant breast cancer (LPBC), with approximately 16% of cancers showing no evidence of TILs. Triple-negative (TN) breast cancers demonstrated the highest incidence of LPBC (20%; range, 4%-37%). This incidence is similar to that of breast cancers that are human epidermal growth factor 2 positive and either hormone receptor positive or negative (HER2+) at 16% (range 11%-24%). Hormone receptor positive/HER2- (HR+) breast cancer showed the lowest incidence of LPBC at 6% (range, 3%-12%). CD8+ T-cell infiltrates, indicative of type I immunity, were found in 48% of all breast cancers (range, 32%-80%) with similar levels observed in TN (60%; range, 40%-91%) and HER2+ disease (61%; range, 40%-83%). Fewer HR+ tumors demonstrated CD8+ TIL (43%; range, 30%-73%). The highest levels of FOXP3+ cells were observed in TN (70%; range, 65%-76%) and HER2+ disease (67%; range, 61%-74%). A minority of HR+ breast cancers demonstrated high levels of tumor-infiltrating FOXP3+ cells (38%; range, 35%-41%). Conclusions and Relevance The magnitude of TIL is variable within and between breast cancer subtypes. Levels of lymphocytic subpopulations may identify breast cancers more amenable to immunomodulation and indicate additional strategies to enhance immunity in patients with low to moderate levels of TILs.
Elementary teachers' perspectives: a qualitative exploration of the role of elementary teachers on the hiring team

In this era of educational accountability, educators, parents, and patrons are interested in finding the most efficient and effective route toward increasing student achievement. Research has shown a highly effective teacher in the classroom as the central component on this path to improved student learning. As school districts restructure their hiring practices to ask teachers to join the principal in selecting the best teacher candidate to hire, new questions arise as to their role on the hiring team. This qualitative research study used an online survey to gather 146 elementary teachers’ perspectives from both a large and small school district in the Pacific Northwest. The study also included four consecutive focus groups, one group consisting of three elementary teachers from the small school district and three groups consisting of a total of 10 elementary teachers from the larger school district, to dig deeper into the practice of distributed leadership as it pertains to the hiring process. This study is based on the theoretical framework of distributed leadership and an extensive study of distributed leadership as a practice of educational reform. It contributes to literature regarding teachers’ perspectives pertaining to their experience and role in the hiring process using a distributed leadership practice in selection of a high quality teacher. The results of this study extend previous findings regarding the degree in which teachers and administrators are involved in the hiring process, and the findings of former studies indicating the relationship between school-based hiring and an effective teacher selection. The outcomes of this study explore teachers’ views as to their role on a hiring team. Additionally, findings offer principals and district hiring personnel insight into elementary teachers’ experiences as a part of the hiring team and explore teachers’ perceptions regarding the practice of distributed leadership in hiring a quality teacher.
Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer.

PURPOSE Patients with colorectal cancer (CRC) and liver metastases have a poor prognosis, but can benefit from perioperative chemotherapy and disease resection. Bevacizumab improves outcomes in patients with metastatic CRC; however, its impact on surgical complications and hepatic regeneration after liver resection remains to be determined. PATIENTS AND METHODS Fifty-six patients with metastatic CRC with liver metastases potentially curable by resection were eligible for this single-center, nonrandomized phase II trial. Eligibility criteria defined patients at high risk of early recurrence. Patients received biweekly bevacizumab plus capecitabine and oxaliplatin for six cycles. The sixth cycle of therapy did not include bevacizumab, resulting in 5 weeks between the last administration of bevacizumab and surgery. RESULTS Objective response to neoadjuvant chemotherapy was achieved in 41 patients (73%). Fifty-two patients underwent liver resection including 11 with synchronous primary tumor resection. No increased intraoperative bleeding events or wound-healing complications were observed and only three patients (6%) required perioperative blood transfusions. Further surgery was necessary in a single patient. Postoperative liver function and regeneration were normal in all but one patient. No postoperative mortality occurred and morbidity was encountered in 11 patients (20%). The mean length of postoperative hospitalization was 9 days (+/- 4.0). CONCLUSION These data suggest that bevacizumab can be safely administered until 5 weeks before liver resection in patients with metastatic CRC without increasing the rate of surgical or wound healing complications or severity of bleeding. To our knowledge, they are also the first to show that neoadjuvant bevacizumab does not affect liver regeneration after resection.
Ventilation conditions and air-borne bacteria and particles in operating theatres: proposed safe economies

SUMMARY Concentrations of air-borne bacteria and particles have been measured in turbulently ventilated operating theatres in full flow, half flow and zero flow conditions. Increased air-borne challenge produced by human activity and by mechanical cleaning procedures is demonstrated: die-away of this contamination is shown to be related to the ventilation rate. Ventilation can be reduced or turned off at night and during weekends, and cleaning can also be carried out, without increased risk of infection if full flow is restored one hour prior to preparation for surgery. Areas surrounding the theatres should remain at positive pressure with regard to the general hospital environment during low or no flow periods. The implementation of such energy-saving policies will substantially reduce theatre running costs without introducing infection hazards.
The Challenges of Globalisation for Civil Servants

Globalisation is an oft-discussed topic today. The role of government in it has been emphasised by both national and international organisations, intellectuals and administrators. However it is necessary to know the role of civil servants in the globalisation process so that government can frame policies for the betterment of the country and its people. In this article an attempt has been made to examine the concept, the good and bad effects of globalisation, the role of civil service, the unfolding scenario and the challenges that civil servants are likely to face in the future.
RISK OF POPULATION EXTINCTION FROM FIXATION OF NEW DELETERIOUS MUTATIONS

The fixation of new deleterious mutations is analyzed for a randomly mating population of constant size with no environmental or demographic stochasticity. Mildly deleterious mutations are far more important in causing loss of fitness and eventual extinction than are lethal and semilethal mutations in populations with effective sizes, Ne, larger than a few individuals. If all mildly deleterious mutations have the same selection coefficient, s against heterozygotes and 2s against homozygotes, the mean time to extinction, t¯ , is asymptotically proportional to e4Nes/Ne for 4Nes > 1. Nearly neutral mutations pose the greatest risk of extinction for stable populations, because the magnitude of selection coefficient that minimizes t¯ is about ŝ = 0.4/Ne. The influence of variance in selection coefficients among mutations is analyzed assuming a gamma distribution of s, with mean s¯ and variance σs2 . The mean time to extinction increases with variance in selection coefficients if s¯ is near ŝ, but can decrease greatly if s¯ is much larger than ŝ. For a given coefficient of variation of s, c=σs/s¯ , the mean time to extinction is asymptotically proportional to Ne1+1/c2 for 4Nes¯>1 . When s is exponentially distributed, (c = 1) t¯ is asymptotically proportional to Ne2 . These results in conjunction with data on the rate and magnitude of mildly deleterious mutations in Drosophila melanogaster indicate that even moderately large populations, with effective sizes on the order of Ne = 103, may incur a substantial risk of extinction from the fixation of new mutations.
Dose-dependent pharmacokinetics of delavirdine in combination with amprenavir in healthy volunteers.

OBJECTIVES To investigate different dose combinations of amprenavir and delavirdine in order to assess an optimal dose suitable for clinical use. METHODS This was a prospective, open-label, controlled, three-period, multiple-dose study with nine healthy volunteers. The volunteers received three different dose combinations of amprenavir and delavirdine twice a day for 10 days with a subsequent 12 h pharmacokinetic evaluation. Combination 1: amprenavir 600 mg and delavirdine 600 mg; combination 2: amprenavir 600 mg and delavirdine 800 mg; combination 3: amprenavir 450 mg and delavirdine 1000 mg. The combinations were taken at least 2 weeks apart. RESULTS Differences in median delavirdine Cmax, C12 and AUC0-12 were seen when comparing the three combinations (3 > 2>1) (P<0.04). A considerable and clinically important higher median C12 was seen with combination 3 when compared to combination 1 (835 to 3944 ng/mL) (P=0.0039). Only small differences in the amprenavir pharmacokinetic parameters were seen between the three dose combinations, with a median C12 of 412, 434 and 536 ng/mL, respectively. CONCLUSIONS In this study, an increase of 472% in median delavirdine C12 was seen with a delavirdine dose increase of only 67% (600 to 1000 mg). Saturation of the CYP3A4 enzymes and/or possibly also P-glycoprotein could be involved. Combination 3 was considered most suitable for clinical use, but because of the large inter-individual variation in steady-state concentrations, the use of the combination should be supported by therapeutic drug monitoring and restricted to certain patients.
Future research trends in the major chemical language of bacteria

Microbiology was revolutionized in the 1990's by the discovery that many different bacterial species coordinate their behavior when they form a group. In fact, bacteria are now considered multicellular organisms capable of communicating and changing behavior in relation to their cell‐density; since 1994 this has been called quorum sensing. This group behavior ensures survival and propagation of the community in many natural environments. Bacterial intercellular communication is mediated by different chemical signals that are synthesized by bacteria which are then either secreted or diffused in the external environment. Bacteria are then able to detect the type and concentration of the signal resulting in regulation of gene expression and, consequently, a synchronized response by the community. The predominant signalling molecules produced by Gram‐negative bacteria are N‐acyl derivatives of homoserine lactone (AHLs) which have been shown to be produced by over seventy bacterial species. In this essay we discuss the importance of quorum sensing via AHLs and highlight current and future trends in this important field of research.
An inventory model for deteriorating item with frequency of advertisement and selling price dependent demand under mixed type trade credit policy

In this paper, we have developed an inventory model for a deteriorating item with selling price and frequency of advertisement dependent demand of an item under the mixed type financial trade credit policy. Shortages are allowed and partially backlogged with a variable rate dependent on the duration of waiting time up to the arrival of next lot. In this model, the deterioration rate follows three-parameter Weibull distribution. Transportation cost is dependent on the lot-size as well as the distance from the source to the destination. The corresponding model has been formulated and solved by generalised reduced gradient-based method. Numerical examples have been considered to discuss the results and the significant features of this model. Finally, based on these examples, the effects of different parameters have been studied by sensitivity analyses taking one parameter at a time keeping the other parameters as same.
Auditor Incentives and the Structure of the Audit Market : A Basic Model for Investigating Simultaneous Effects of Audit Market Regulations

For decades, legislators worldwide have been discussing the merits of regulating their national audit markets. In this debate, the focus has primarily been on the regulations’ effects on incentives, both those of preparers of financial statements to report truthfully and those of auditors to detect errors or even fraud and to correctly report their findings to the public. For some of the proposed measures, the empirical evidence as to whether they indeed improve such incentives remains inconclusive. In addition, there is a concern that certain regulations could negatively affect the structure of the audit market. Changes in the market structure, in turn, can either attenuate or reinforce the regulations’ effects on preparers’ and auditors’ incentives. To a large extent, this unintended side-effect has been neglected in the discussions. We adapt a spatial competition model to the audit market. This model allows simultaneously analyzing the incentive and market structure effects resulting from regulations and thus determining their overall impact.
Constructing and Maintaining Legitimacy: Sociological Perspectives of the Politics of Central Banking

This working paper reviews central banking research produced in sociology and anthropology, most of which has been published in the last five to ten years. These studies focus on institutional structures and social and cultural processes that shape central bank activity, with significant attention to the ways in which central banks seek to legitimate their actions. I outline key themes that have emerged, including central banks’ internal decision-making and analysis of the international pressures they face. I review research examining the ways in which central bankers are influenced by one another, use performative rhetoric to manage the market, and engage in relational work with a variety of actors as they seek to maintain their legitimacy. This research is an important complement to traditional central banking research published in the fields of economics, political science, and law, and underscores the complexity involved in the day-to-day operations of central banks.
How to understand, evaluate and influence efficient progress in South Africa’s land reform process: A typology from historical lessons from selected sub-Saharan African countries

Background: With reports of widespread failures in South Africa’s land reform programmes, the levels of policy uncertainty in the political rhetoric that influences land reform have been increasing. Since 1994 policy targets to transfer land to black farmers have not been met. Of the 2005 target to transfer about 25 million ha of commercial farmland to black farmers by 2014, less than 5 million ha. have been transferred for commercial use. Some studies report failure rates in resettlement projects of up to 90%. To account for the failures, revisions of policies and amendments to legislations have been proposed within a political environment that is becoming increasingly intolerant to slow progress in land transfers and to resettlement failures. Aim: Against this environment, this paper presents a typology for understanding and evaluating important elements of the land reform project in order to influence progress in the process. Setting: The study adopts a historical review of land reform processes in post-colonial Kenya and Zimbabwe in order to identify potential challenges and key lessons for South Africa. Methods: Hence, using institutional and historical analytical lenses in exploring different narratives, the paper reviews reported failures and successes in land reform policy cases from the selected countries. From an institutional framework, prevalent social institutions and key lessons from Kenya, Zimbabwe and South Africa, a typology for evaluating important elements of the land reform process in South Africa is developed and discussed. Additionally, a review of global data collected on average sizes of farms in different regions of the world is provided as evidence to support propositions of what would constitute efficient farmland size ranges for small to medium commercial farms in South Africa. Results and conclusion: A proposition is made on how to use the typology to guide policy and research interventions to reduce failures and promote successful cases in different areas of the land reform process in South Africa, and possibly other similar contexts.
Parenteral ascorbate as a cancer therapeutic: a reassessment based on pharmacokinetics.

SIGNIFICANCE Ewan Cameron reported that ascorbate, given orally and intravenously at doses of up to 10 g/day, was effective in the treatment of cancer. Double-blind placebo-controlled clinical trials showed no survival advantage when the same doses of ascorbate were given orally, leading the medical and scientific communities to dismiss the use of ascorbate as a potential cancer treatment. However, the route of administration results in major differences in ascorbate bioavailability. Tissue and plasma concentrations are tightly controlled in response to oral administration, but this can be bypassed by intravenous administration. These data provide a plausible scientific rationale for the absence of a response to orally administered ascorbate in the Mayo clinic trials and indicate the need to reassess ascorbate as a cancer therapeutic. RECENT ADVANCES High dose ascorbate is selectively cytotoxic to cancer cell lines through the generation of extracellular hydrogen peroxide (H2O2). Murine xenograft models confirm a growth inhibitory effect of pharmacological concentrations. The safety of intravenous ascorbate has been verified in encouraging pilot clinical studies. CRITICAL ISSUES Neither the selective toxicity of pharmacologic ascorbate against cancer cells nor the mechanism of H2O2-mediated cytotoxicity is fully understood. Despite promising preclinical data, the question of clinical efficacy remains. FUTURE DIRECTIONS A full delineation of mechanism is of interest because it may indicate susceptible cancer types. Effects of pharmacologic ascorbate used in combination with standard treatments need to be defined. Most importantly, the clinical efficacy of ascorbate needs to be reassessed using proper dosing, route of administration, and controls.
Soay rams target reproductive activity towards promiscuous females’ optimal insemination period

Female promiscuity is thought to have resulted in the evolution of male behaviours that confer advantages in the sperm competition that ensues. In mammalian species, males can gain a post–copulatory advantage in this sperm ‘raffle’ by inseminating females at the optimal time relative to ovulation, leading to the prediction that males should preferentially associate and copulate with females at these times. To the best of our knowledge, we provide the first high–resolution test of this prediction using feral Soay sheep, which have a mating system characterized by male competition for access to highly promiscuous females. We find that competitive males time their mate guarding (and hence copulations) to occur close to the optimal insemination period (OIP), when females are also increasingly likely to ’cooperate’ with copulation attempts. Subordinate males practice an alternative mating tactic, where they break the integrity of the consort pair and force copulations on females. The timing of these forced copulations is also targeted towards the OIP. We thus provide quantitative evidence that female promiscuity has resulted in the evolution of reproductive strategies in which males ’load’ the sperm raffle by targeting their mating activity towards female OIPs, when the probability of sperm–competition success is at its greatest.
Subtype‐specific problems with quantification of plasma HIV‐1 RNA

Objective: To determine whether two commercial assays for quantification of plasma HIV‐1 RNA levels detect different genetic subtypes of HIV‐1 with equal efficiency. Design: Blind testing of stored plasma samples from 95 individuals infected with different genetic subtypes of HIV‐1 (27 subtype A, 24 B, 18 C, 18 D, two E, two G, two H, and two J). The HIV‐1 subtype had previously been determined by direct sequencing of the V3 domain of the env gene. Methods: One plasma sample from each individual was tested once by the Roche HIV monitor assay and once by the Organon nucleic acid sequence‐based amplification (NASBA) HIV‐1 RNA quantitative assay, according to the manufacturers' recommendations. Information about CD4+ lymphocyte counts and antiretroviral treatment was available. Results: The results from the two assays were strongly correlated with each other for subtypes B, C and D, but not for subtype A because many samples had RNA levels close to or below the lower detection limit of the assays. Thus, 15 out of 27 (56%) subtype A samples were negative by the HIV monitor assay and 12 (44%) were negative by the NASBA assay. These frequently occurring negative results among subtype‐A‐infected individuals were not due to better immunological status, more aggressive antiretroviral treatment, or differences in sample storage conditions. Conclusions: The HIV monitor assay and, possibly to slightly lesser degree, the NASBA assay appear unable to accurately quantify HIV‐1 RNA levels in plasma samples from many subtype‐A‐infected individuals. These problems are likely to be due to primer mismatches and they limit the possibility of using these assays for routine monitoring of HIV‐1‐infected individuals in many parts of the world.