Posttransplant Thrombopoiesis Predicts Survival in Patients Undergoing Autologous Hematopoietic Progenitor Cell Transplantation

AbstractThe frequency and clinical significance of secondary thrombocytopenia following initial engraftment in autologous hematopoietic progenitor cell transplantation (HPCT) is unknown. An institutional review board approved retrospective study of thrombopoiesis was performed in 359 patients transplanted with autologous blood (97%) or marrow (3%) who achieved platelet engraftment to >50,000/μL. Idiopathic secondary posttransplant thrombocytopenia (ISPT) was defined as >50% decline in blood platelets to <100,000/μL in the absence of relapse or sepsis. ISPT occurred at a median of day +35 posttransplant in 17% of patients. Patients with ISPT had similar initial platelet engraftment (median 17 days) versus non-ISPT patients (18 days; P = NS) and recovered platelet counts (median 123,00 K/μL) by day 110 posttransplant. Four factors were independently associated with post-transplant death in a multivariate model: disease status at transplant; the number of prior chemotherapy regimens, failure to achieve a platelet count of >150,000/μL posttransplant, and the occurrence of ISPT. A prognostic score was developed based upon the occurrence of ISPT and posttransplant platelet counts of <150,000/μL. Survival of patients with both factors (n = 25) was poor (15% alive at 5 years); patients with 1 factor (n = 145) had 49% 5-year survival; patients with 0 factors (n = 189) had 72% 5-year survival. Patients who failed to achieve a platelet count of >150,000/μL received significantly fewer CD34+ cells/kg (P < .001), whereas patients with ISPT received fewer CD34+CD38− cells/kg (P = .0006). The kinetics of posttransplant thrombopoiesis is an independent prognostic factor for long-term survival following autologous HPC. ISPT and lower initial posttransplant platelet counts reflect poor engraftment with long-term and short-term repopulating CD34+ hematopoietic stem cells, respectively, and are associated with an increased risk of death from disease relapse

Population-Level Compensation Impedes Biological Control of an Invasive Forb and Indirect Release of a Native Grass

The intentional introduction of specialist insect herbivores for biological control of exotic weeds provides ideal but understudied systems for evaluating important ecological concepts related to top-down control, plant compensatory responses, indirect effects, and the influence of environmental context on these processes. Centaurea stoebe (spotted knapweed) is a notorious rangeland weed that exhibited regional declines in the early 2000s, attributed to drought by some and to successful biocontrol by others. We initiated an experiment to quantify the effects of the biocontrol agent, Cyphocleonus achates, on Ce. stoebe and its interaction with a dominant native grass competitor, Pseudoroegneria spicata, under contrasting precipitation conditions. Plots containing monocultures of each plant species or equal mixtures of the two received factorial combinations of Cy. achates herbivory (exclusion or addition) and precipitation (May–June drought or “normal,” defined by the 50-year average) for three years. Cy. achates herbivory reduced survival of adult Ce. stoebe plants by 9% overall, but this effect was stronger under normal precipitation compared to drought conditions, and stronger in mixed-species plots compared to monocultures. Herbivory had no effect on Ce. stoebe per capita seed production or on recruitment of seedlings or juveniles. In normal-precipitation plots of mixed composition, greater adult mortality due to Cy. achates herbivory resulted in increased recruitment of new adult Ce. stoebe. Due to this compensatory response to adult mortality, final Ce. stoebe densities did not differ between herbivory treatments regardless of context. Experimental drought reduced adult Ce. stoebe survival in mixed-species plots but did not impede recruitment of new adults or reduce final Ce. stoebe densities, perhaps due to the limited duration of the treatment. Ce. stoebe strongly depressed P. spicata reproduction and recruitment, but these impacts were not substantively alleviated by herbivory on Ce. stoebe. Population-level compensation by dominant plants may be an important factor inhibiting top-down effects in herbivore-driven and predator-driven cascades

The beginning of time? Evidence for catastrophic drought in Baringo in the early nineteenth century

New developments in the collection of palaeo-data over the past two decades have transformed our understanding of climate and environmental history in eastern Africa. This article utilises instrumental and proxy evidence of historical lake-level fluctuations from Baringo and Bogoria, along with other Rift Valley lakes, to document the timing and magnitude of hydroclimate variability at decadal to century time scales since 1750. These data allow us to construct a record of past climate variation not only for the Baringo basin proper, but also across a sizable portion of central and northern Kenya. This record is then set alongside historical evidence, from oral histories gathered amongst the peoples of northern Kenya and the Rift Valley and from contemporary observations recorded by travellers through the region, to offer a reinterpretation of human activity and its relationship to environmental history in the nineteenth century. The results reveal strong evidence of a catastrophic drought in the early nineteenth century, the effects of which radically alters our historical understanding of the character of settlement, mobility and identity within the Baringo–Bogoria basin

Consensus document on the progression and treatment response criteria in gastroenteropancreatic neuroendocrine tumors

Purpose Gastroenteropancreatic neuroendocrine tumors are a heterogeneous group of low incidence neoplasms characterized by a low proliferative activity and slow growth. Their response to targeted therapies is heterogeneous and often does not lead to tumor shrinkage. Thus, evaluation of the therapeutic response should difer from other kind of tumors. Methods To answer relevant questions about which techniques are best in the assessment of progression or treatment response a RAND/UCLA-based consensus process was implemented. Relevant clinical questions were listed followed by a systematic search of the literature. The expert panel answered all questions with recommendations, combining available evidence and expert opinion. Recommendations were validated through a questionnaire and a participatory meeting. Results Expert recommendations regarding imaging tools for tumor assessment and evaluation of progression were agreed upon. Available imaging techniques were reviewed and recommendations for best patient monitoring practice and the best way to evaluate treatment response were formulated

US Patent 7,577,612 B2 Self Service Terminal

The invention of a wireless mobile telephone operated ATM machine that is able to execute a transaction using a cellular network or wireless network

Recovery of Wolverines in the Western United States: Recent Extirpation and Recolonization or Range Retraction and Expansion?

Wolverines were greatly reduced in number and possibly extirpated from the contiguous United States (U.S.) by the early 1900s. Wolverines currently occupy much of their historical range in Washington, Idaho, Montana, and Wyoming, but are absent from Utah and only single individuals are known to occur in California and Colorado. In response, the translocation of wolverines to California and Colorado is being considered. If wolverines are to be reintroduced, managers must identify appropriate source populations based on the genetic affinities of historical and modern wolverine populations. We amplified the mitochondrial control region of 13 museum specimens dating from the late 1800s to early 1900s and 209 wolverines from modern populations in the contiguous U.S. and Canada and combined results with previously published haplotypes. Collectively, these data indicated that historical wolverine populations in the contiguous U.S. were extirpated by the early 20th century, and that modern populations in the contiguous U.S. are likely the descendants of recent immigrants from the north. The Cali1 haplotype previously identified in California museum specimens was also common in historical samples from the southern Rocky Mountains, and likely evolved in isolation in the southern ice-free refugium that encompassed most of the contiguous U.S. during the last glaciation. However, when southern populations were extirpated, these matrilines were eliminated. Several of the other haplotypes found in historical specimens from the contiguous U.S. also occur in modern North American populations, and belong to a group of haplotypes that are associated with the rapid expansion of northern wolverine populations after the last glacial retreat. Modern wolverines in the contiguous U.S. are primarily haplotype A, which is the most common and widespread haplotype in Canada and Alaska. For the translocation of wolverines to California, Colorado, and other areas in the western U.S., potential source populations in the Canadian Rocky Mountains may provide the best mix of genetic diversity and appropriate learned behavior

The Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of acute leukemia.

Acute leukemia is a constellation of rapidly progressing diseases that affect a wide range of patients regardless of age or gender. Traditional treatment options for patients with acute leukemia include chemotherapy and hematopoietic cell transplantation. The advent of cancer immunotherapy has had a significant impact on acute leukemia treatment. Novel immunotherapeutic agents including antibody-drug conjugates, bispecific T cell engagers, and chimeric antigen receptor T cell therapies have efficacy and have recently been approved by the US Food and Drug Administration (FDA) for the treatment of patients with acute leukemia. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to develop a clinical practice guideline composed of consensus recommendations on immunotherapy for the treatment of acute lymphoblastic leukemia and acute myeloid leukemia

"It's a can of worms": understanding primary care practitioners' behaviours in relation to HPV using the Theoretical Domains Framework

Background: The relationship between infection with high-risk human papillomavirus (HPV) and cervical cancer is transforming cervical cancer prevention. HPV tests and vaccinations have recently become available. In Ireland, as elsewhere, primary care practitioners play a key role in prevention. ATHENS (A Trial of HPV Education and Support) aims to develop a theorybased intervention to support primary care practitioners in their HPV-related practice. This study, the first step in the intervention development process, aimed to: identify HPV-related clinical behaviours that the intervention will target; clarify general practitioners’ (GPs’) and practice nurses’ roles and responsibilities; and determine factors that potentially influence clinical behaviour. A secondary objective was to informally assess the utility of the Theoretical Domains Framework (TDF) in understanding clinical behaviours in an area with an evolving evidence-base. Methods: In-depth semi-structured telephone interviews were conducted with GPs and practice nurses. The topic guide, which contained open questions and HPV-related clinical scenarios, was developed through literature review and clinical experience. Interview transcripts were content-analysed using the TDF as the coding framework. Results: 19 GPs and 14 practice nurses were interviewed. The major HPV-related clinical behaviours were: initiating a discussion about HPV infection with female patients; offering/recommending HPV vaccination to appropriate patients; and answering patients’ questions about HPV testing. While the responsibility for taking smears was considered a female role, both male and female practitioners dealt with HPV-related issues. All 12 theoretical domains arose in relation to HPV infection; the domains judged to be most important were: knowledge, emotion, social influences, beliefs about capabilities and beliefs about consequences. Eleven domains emerged in relation to HPV vaccination, with beliefs about consequences, social influences, knowledge and environmental context and resources judged to be the most important. Nine domains were relevant to HPV testing, with knowledge and beliefs about capabilities judged to be the most important. Conclusions: The findings confirm the need for an intervention to support primary care practitioners around HPV and suggest it should target a range of theoretical domains. The TDF proved valuable in analysing qualitative data collected using a topic guide not specifically designed to capture TDF domains and understanding clinical behaviours in an area with an evolving evidence-base