Allo-HSCT in transplant-naive patients with Hodgkin lymphoma: a single-arm, multicenter study

We evaluated the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in transplant-naïve patients with relapsed/refractory Hodgkin lymphoma (HL) who failed to attain metabolic complete response (mCR) to 1 to 2 lines of salvage chemotherapyThose with residual but nonprogressive disease assessed by positron emission tomography/computed tomography scanning were eligible. An additional 1 to 2 cycles of salvage therapy were permissible in those with progressive disease or when required to bridge to allo-HSCT, with additional imaging at baseline before transplantation. Conditioning consisted of carmustine, etoposide, cytarabine, melphalan, and alemtuzumab. Donor lymphocyte infusions (DLI) were administered for mixed chimerism or residual or relapsed disease. Eleven patients had sibling donors, 13 had HLA-matched unrelated donors, and 7 had HLA-mismatched unrelated donors. There were no graft failures, and no episodes of grade 4 acute graft-versus-host disease (GVHD); only 19.4% of patients had grade 2 to 3 GVHD, and 22.2% had extensive chronic GVHD. The non-relapse mortality rate was 16.1% (95% confidence interval [CI], 7.1%-34.5%). Relapse incidence was 18.7% (95% CI, 8.2%-39.2%). The study met its primary objective, with a 3-year progression-free survival of 67.7% (95% CI, 48.4%-81.2%). Survival outcomes were equivalent in those with residual metabolically active disease immediately before transplantation (n = 24 [70.8%; 95% CI, 17.2%-83.7%]). Two of the 5 patients who relapsed received DLI and remained in mCR at latest follow-up, with a 3-year overall survival of 80.7% (95% CI, 61.9%-90.8%). We demonstrate encouraging results that establish a potential role for allo-HSCT in selected high-risk patients with HL. This trial was registered at www.clinicaltrials.gov as #NCT00908180

Trends in cow numbers and culling rate in the Irish cattle population, 2003 to 2006

Cows are the main economic production units of Ireland's cattle industry. Therefore, demographic information, including overall numbers and survival rates, are relevant to the Irish agricultural industry. However, few data are available on the demographics of cows within a national population, either in Ireland or elsewhere, despite the recent development of comprehensive national cattle databases in many EU Member States. This study has sought: to determine the rate of cow culling from the national herd; to determine the rate of culling by type (dairy, beef), age, method of exit, date of exit and interval between last calving and exit; to calculate the national cow on-farm mortality rate; and to compare the Irish rates with published data from other countries. This work was conducted using data recorded in the national Cattle Movement Monitoring System (CMMS). Culling refers to the exit of cows from the national herd, as a result of death but regardless of reason, and cow-culling rate was calculated as the number of cow exits (as defined above) each year divided by the number of calf births in the same year. Culling rate was determined by type (dairy or beef), date of birth, method of exit (slaughter or on-farm death), month of exit and interval between last calving and exit. The average cow-culling rate during 2003 to 2006 was 19.6% (21.3% for dairy, 18% for beef). While comparisons must be treated with caution, it concluded that the overall rates of culling in Ireland fell within published internationally accepted norms. The on-farm mortality rate of 3.2-4.1% was similar to that reported in comparable studies

Pavlovian Fear Conditioning Activates a Common Pattern of Neurons in the Lateral Amygdala of Individual Brains

Understanding the physical encoding of a memory (the engram) is a fundamental question in neuroscience. Although it has been established that the lateral amygdala is a key site for encoding associative fear memory, it is currently unclear whether the spatial distribution of neurons encoding a given memory is random or stable. Here we used spatial principal components analysis to quantify the topography of activated neurons, in a select region of the lateral amygdala, from rat brains encoding a Pavlovian conditioned fear memory. Our results demonstrate a stable, spatially patterned organization of amygdala neurons are activated during the formation of a Pavlovian conditioned fear memory. We suggest that this stable neuronal assembly constitutes a spatial dimension of the engram

A study of tuberculosis in road traffic-killed badgers on the edge of the British bovine TB epidemic area

The role of badgers in the geographic expansion of the bovine tuberculosis (bTB) epidemic in England is unknown: indeed there have been few published studies of bTB in badgers outside of the Southwest of England where the infection is now endemic in cattle. Cheshire is now on the edge of the expanding area of England in which bTB is considered endemic in cattle. Previous studies, over a decade ago when bovine infection was rare in Cheshire, found no or only few infected badgers in the south eastern area of the county. In this study, carried out in 2014, road-killed badgers were collected through a network of local stakeholders (farmers, veterinarians, wildlife groups, government agencies), and Mycobacterium bovis was isolated from 21% (20/94) badger carcasses. Furthermore, there was strong evidence for co-localisation of M. bovis SB0129 (genotype 25) infection in both badgers and cattle herds at a county scale. While these findings suggest that both badgers and cattle are part of the same geographically expanding epidemic, the direction of any cross-species transmission and the drivers of this expansion cannot be determined. The study also demonstrated the utility of using road-killed badgers collected by stakeholders as a means of wildlife TB surveillance

Lynch syndrome: barriers to and facilitators of screening and disease management

Background Lynch syndrome is a hereditary cancer with confirmed carriers at high risk for colorectal (CRC) and extracolonic cancers. The purpose of the current study was to develop a greater understanding of the factors influencing decisions about disease management post-genetic testing. Methods The study used a grounded theory approach to data collection and analysis as part of a multiphase project examining the psychosocial and behavioral impact of predictive DNA testing for Lynch syndrome. Individual and small group interviews were conducted with individuals from 10 families with the MSH2 intron 5 splice site mutation or exon 8 deletion. The data from confirmed carriers (n = 23) were subjected to re-analysis to identify key barriers to and/or facilitators of screening and disease management. Results Thematic analysis identified personal, health care provider and health care system factors as dominant barriers to and/or facilitators of managing Lynch syndrome. Person-centered factors reflect risk perceptions and decision-making, and enduring screening/disease management. The perceived knowledge and clinical management skills of health care providers also influenced participation in recommended protocols. The health care system barriers/facilitators are defined in terms of continuity of care and coordination of services among providers. Conclusions Individuals with Lynch syndrome often encounter multiple barriers to and facilitators of disease management that go beyond the individual to the provider and health care system levels. The current organization and implementation of health care services are inadequate. A coordinated system of local services capable of providing integrated, efficient health care and follow-up, populated by providers with knowledge of hereditary cancer, is necessary to maintain optimal health

Contrasting resource allocation patterns in Sedum lanceolatum Torr.: Biomass versus energy estimates

Biomass determinations and microbomb calorimetry were used to assess resource allocation in Sedum lanceolatum Torr. between 2,257 and 3,726 m above sea level in the Front Range of the Rocky Mountains, Colorado, USA. In general, energy values did not differ within a tissue among sites, but did differ among tissue types. Flowers and leaves had the greatest energy content per gram ashfree dry weight. Total kilojoules per plant were homogeneous along the elevational gradient.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47753/1/442_2004_Article_BF00379785.pd

Primary graft failure, but not relapse, may be identified by early chimerism following double cord unit transplantation

Key Points Primary graft failure may be identified by early chimerism analysis following double cord blood unit transplantation with reduced intensity conditioning. Chimerism does not appear to be useful in predicting relapse. Umbilical cord blood transplantation (UCBT) has increased access to potentially curative therapy for patients with life-threatening disorders of the bone marrow and immune system. The introduction of reduced intensity conditioning (RIC) regimens and double cord unit infusions (DUCBT) has broadened the applicability of UCBT to more frail or larger recipients. The kinetics of chimerism following RIC DUCBT and their clinical utility are poorly understood. The RIC CBT trial reported here sought to prospectively evaluate the role of lineage specific chimerism following DUCBT in adult patients with haematological malignancies in the UK. Fifty-eight patients with a median age of 52 years were recruited, with an overall and progression free survival of 59% (95%CI 45% to 71%) and 52% (95%CI 39% to 64%) respectively at 2 years. Nonrelapse mortality was 4% (95% CI 1% to 13%) at day 100 and the relapse rate was 31% (95%CI 21% to 45%) at 1 year. Peripheral blood lineage specific chimerism was feasible from day 7 post-transplant onwards. Five patterns of chimerism were observed including i) complete single unit dominance (39 patients), ii) sustained donor-donor mixed chimerism (3 patients), iii) sustained donor-recipient mixed chimerism (5 patients), iv) dominance reversion (1 patient) and v) primary graft failure (4 patients). The RIC CBT trial enabled adult patients with high-risk hematological malignancies to safely access UCBT in the UK and provided novel insights into the kinetics of donor and recipient chimerism following RIC DUCBT which are clinically relevant. (Clinical Trials.gov identifier: NCT00959231; EudraCT identifier: 2004-003845-41)

A case of mistaken identity

What went wrong between the UK media and a report on 'multi-ethnic' Britain