Patients with multiple myeloma progressing on current therapies have limited treatment options. Pomalidomide (CC4047), an immunomodulatory drug, has significant activity in relapsed myeloma and ...previous studies suggest activity in lenalidomide refractory disease. To better define its efficacy in this group, we treated a cohort of lenalidomide refractory patients. Pomalidomide was given orally (2 mg) daily, continuously in 28-day cycles along with dexamethasone (40 mg) given weekly. Responses were assessed by the International Myeloma Working Group Criteria. Thirty-four patients were enrolled. The best response was very good partial response in 3 (9%), partial response (PR) in 8 (23%), best responses (MR) in 5 (15%), stable disease in 12 (35%) and progressive disease in 6 (18%), for an overall response rate of 47%. Of the 14 patients that were considered high risk, 8 (57%) had responses including 4 PR and 4 MR. The median time to response was 2 months and response duration was 9.1 months, respectively. The median overall survival was 13.9 months. Toxicity was primarily hematologic, with grade 3 or 4 toxicity seen in 18 patients (53%) consisting of anemia (12%), thrombocytopenia (9%) and neutropenia (26%). The combination of pomalidomide and dexamethasone (Pom/dex) is highly active and well tolerated in patients with lenalidomide-refractory myeloma.
Background
The objective of this study was to describe the first US‐based study to use the European Position Paper on Rhinosinusitis (EPOS) criteria to study the prevalence of chronic rhinosinusitis ...(CRS) in a general‐population sample.
Methods
A CRS symptom questionnaire was mailed to 23 700 primary care patients from Geisinger Clinic, a health system serving 45 counties in Pennsylvania. CRS cases were categorized into four unique subgroups based on EPOS symptoms: obstruction and discharge with no smell loss or pain/pressure; smell loss without pain/pressure; facial pain and/or pressure without smell loss; and both smell loss and pain/pressure. All cases were required to have nasal obstruction or discharge. Logistic regression was used to evaluate potential factors associated with CRS subgroups.
Results
We found that 11.9% of patients met criteria for CRS. Prevalence peaked at 15.9% between ages 50 and 59 years and then dropped to 6.8% after age 69. The odds of CRS was higher among patients who were white, younger, smokers, had a history of Medical Assistance, and had other diseases. When CRS subgroups were modeled separately, these associations were no longer significant for some CRS subgroups. Comorbid diseases were most strongly associated with CRS cases who reported smell loss and facial pain and/or pressure and had the weakest associations with CRS cases who did not report these symptoms.
Conclusions
CRS is a highly prevalent and heterogeneous condition. Differences in risk factors and health outcomes across symptom subgroups may be indicative of differences in etiology that have implications for disease management.
Aims. The shape of low-frequency radio continuum spectra of normal galaxies is not well understood, the key question being the role of physical processes such as thermal absorption in shaping them. ...In this work we take advantage of the LOFAR Multifrequency Snapshot Sky Survey (MSSS) to investigate such spectra for a large sample of nearby star-forming galaxies. Methods. Using the measured 150 MHz flux densities from the LOFAR MSSS survey and literature flux densities at various frequencies we have obtained integrated radio spectra for 106 galaxies characterised by different morphology and star formation rate. The spectra are explained through the use of a three-dimensional model of galaxy radio emission, and radiation transfer dependent on the galaxy viewing angle and absorption processes. Results. Our galaxies’ spectra are generally flatter at lower compared to higher frequencies: the median spectral index αlow measured between ≈50 MHz and 1.5 GHz is −0.57 ± 0.01 while the high-frequency one αhigh, calculated between 1.3 GHz and 5 GHz, is −0.77 ± 0.03. As there is no tendency for the highly inclined galaxies to have more flattened low-frequency spectra, we argue that the observed flattening is not due to thermal absorption, contradicting the suggestion of Israel & Mahoney (1990, ApJ, 352, 30). According to our modelled radio maps for M 51-like galaxies, the free-free absorption effects can be seen only below 30 MHz and in the global spectra just below 20 MHz, while in the spectra of starburst galaxies, like M 82, the flattening due to absorption is instead visible up to higher frequencies of about 150 MHz. Starbursts are however scarce in the local Universe, in accordance with the weak spectral curvature seen in the galaxies of our sample. Locally, within galactic disks, the absorption effects are distinctly visible in M 51-like galaxies as spectral flattening around 100–200 MHz in the face-on objects, and as turnovers in the edge-on ones, while in M 82-like galaxies there are strong turnovers at frequencies above 700 MHz, regardless of viewing angle. Conclusions. Our modelling of galaxy spectra suggests that the weak spectral flattening observed in the nearby galaxies studied here results principally from synchrotron spectral curvature due to cosmic ray energy losses and propagation effects. We predict much stronger effects of thermal absorption in more distant galaxies with high star formation rates. Some influence exerted by the Milky Way’s foreground on the spectra of all external galaxies is also expected at very low frequencies.
Non-native plants may benefit, briefly or permanently, from natural enemy release in their invaded range, or may form novel interactions with native enemy species. Likewise, newly arrived herbivores ...may develop novel associations with native plants or, where their hosts have arrived ahead of them, re-establish interactions that existed previously in their ancestral ranges. Predicting outcomes from this diversity of novel and re-established interactions between plants and their herbivores presents a major challenge for invasion biology. We report on interactions between the recently arrived invasive planthopper
Prokelisia marginata
, and the multi-ploidy
Spartina
complex of four native and introduced species in Britain, each representing a different level of shared evolutionary history with the herbivore. As predicted,
S. alterniflora
, the ancestral host, was least impacted by planthopper herbivory, with the previously unexposed native
S. maritima
, a nationally threatened species, suffering the greatest impacts on leaf length gain, new leaf growth and relative water content. Contrary to expectations, glasshouse trials showed
P. marginata
to preferentially oviposit on the invasive allododecaploid
S. anglica
, on which it achieved earlier egg hatch, faster nymphal development, larger female body size and greatest final population size. We suggest
P. marginata
is in the process of rapid adaptation to maximise its performance on what is now the most abundant and widespread host in Britain. The diversity of novel and re-established interactions of the herbivore with this multi-ploidy complex makes this a highly valuable system for the study of the evolutionary ecology of plant–insect interactions and their influence on invasion dynamics.
We present the results of a four-month campaign searching for low-frequency radio transients near the North Celestial Pole with the Low-Frequency Array (LOFAR), as part of the Multifrequency Snapshot ...Sky Survey (MSSS). The data were recorded between 2011 December and 2012 April and comprised 2149 11-min snapshots, each covering 175 deg2. We have found one convincing candidate astrophysical transient, with a duration of a few minutes and a flux density at 60 MHz of 15–25 Jy. The transient does not repeat and has no obvious optical or high-energy counterpart, as a result of which its nature is unclear. The detection of this event implies a transient rate at 60 MHz of
$3.9^{+14.7}_{-3.7}\times 10^{-4}$
d−1 deg−2, and a transient surface density of 1.5 × 10−5 deg−2, at a 7.9-Jy limiting flux density and ∼10-min time-scale. The campaign data were also searched for transients at a range of other time-scales, from 0.5 to 297 min, which allowed us to place a range of limits on transient rates at 60 MHz as a function of observation duration.
OPTN/SRTR 2012 Annual Data Report: Kidney Matas, A. J.; Smith, J. M.; Skeans, M. A. ...
American journal of transplantation,
January 2014, 2014-Jan, 2014-01-00, 20140101, Letnik:
14, Številka:
S1
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
For most end‐stage renal disease patients, successful kidney transplant provides substantially longer survival and better quality of life than dialysis, and preemptive transplant is ...associated with better outcomes than transplants occurring after dialysis initiation. However, kidney transplant numbers in the us have not changed for a decade. Since 2004, the total number of candidates on the waiting list has increased annually. Median time to transplant for wait‐listed adult patients increased from 2.7 years in 1998 to 4.2 years in 2008. The discard rate of deceased donor kidneys has also increased, and the annual number of living donor transplants has decreased. The number of pediatric transplants peaked at 899 in 2005, and has remained steady at approximately 750 over the past 3 years; 40.9% of pediatric candidates undergo transplant within 1 year of wait‐listing. Graft survival continues to improve for both adult and pediatric recipients. Kidney transplant is one of the most cost‐effective surgical interventions; however, average reimbursement for recipients with primary Medicare coverage from transplant through 1 year posttransplant was comparable to the 1‐year cost of care for a dialysis patient. Rates of rehospitalization are high in the first year posttransplant; annual costs after the first year are lower.
Objective
To assess the effect of short message service (SMS) communication on facility delivery, exclusive breastfeeding (EBF), and contraceptive use.
Design
Mobile WACh was a three‐arm unblinded ...individually randomised controlled trial.
Setting
A public sector maternal child health (MCH) clinic in Nairobi, Kenya.
Population
Three hundred women attending antenatal care were randomised, 100 to each arm, and followed for 24 weeks postpartum. Pregnant women, at least 14 years old with access to a mobile phone and able to read SMS were eligible for participation.
Methods
Women were randomised (1:1:1) to receive one‐way SMS versus two‐way SMS with a nurse versus control. Weekly SMS content was tailored for maternal characteristics and pregnancy or postpartum timing.
Main outcome measures
Facility delivery, EBF, and contraceptive use were compared separately between each intervention arm and the control arm by Kaplan–Meier analysis and chi‐square tests using intent‐to‐treat analyses.
Results
The overall facility delivery rate was high (98%) and did not differ by arm. Compared with controls, probability of EBF was higher in the one‐way SMS arm at 10 and 16 weeks, and in the two‐way SMS arm at 10, 16, and 24 weeks (P < 0.005 for all). Contraceptive use was significantly higher in both intervention arms by 16 weeks (one‐way SMS: 72% and two‐way SMS: 73%; P = 0.03 and P = 0.02 versus 57% control, respectively); however, this difference was not significant when correcting for multiple comparisons.
Conclusion
One‐way and two‐way SMS improved EBF practices and early contraceptive use. Two‐way SMS had an added benefit on sustained EBF, providing evidence that SMS messaging influences uptake of interventions that improve maternal and neonatal health.
Source of funding
Funding was provided by the National Institutes of Health (K12HD001264 to JAU, R01HD080460, K24HD054314 to GJS, and K01AI116298 to ALD), the National Science Foundation (Graduate Research Fellowship to TP and BD), as well as the University of Washington Global Center for Integrated Health of Women Adolescents and Children (Global WACh).
Tweetable
The Mobile WACh RCT demonstrates that SMS improved practice of exclusive breastfeeding and early postpartum contraception.
Tweetable
The Mobile WACh RCT demonstrates that SMS improved practice of exclusive breastfeeding and early postpartum contraception.
OPTN/SRTR 2013 Annual Data Report: Kidney Matas, A. J.; Smith, J. M.; Skeans, M. A. ...
American journal of transplantation,
January 2015, 2015-Jan, 2015-01-00, 20150101, Letnik:
15, Številka:
S2
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
A new kidney allocation system, expected to be implemented in late 2014, will characterize donors on a percent scale (0%‐100%) using the kidney donor profile index (KDPI). The 20% of ...deceased donor kidneys with the greatest expected posttransplant longevity will be allocated first to the 20% of candidates with the best expected posttransplant survival; kidneys that are not accepted will then be offered to remaining 80% of candidates. Waiting time will start at the time of maintenance dialysis initiation (even if before listing) or at the time of listing with an estimated glomerular filtration rate of 20 mL/min/1.73 m2 or less. Under the current system, the number of candidates on the waiting list continues to increase, as each year more candidates are added than are removed. Median waiting times for adults increased from 3 years in 2003 to more than 4.5 years in 2009. Donation rates have not increased. Short‐term outcomes continue to improve; death‐censored graft survival at 90 days posttransplant was 97% or higher for deceased donor transplants and over 99% for living donor transplants. In 2013, 883 pediatric candidates were added to the waiting list; 65.8% of pediatric candidates on the list in 2013 underwent deceased donor transplant. Five‐year graft survival was highest for living donor recipients aged younger than 11 years (89%) and lowest for deceased donor recipients aged 11 to 17 years (68%).
Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair ...functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1065 families (containing 1406 patients with OCD), combined with population-based samples (resulting in a total sample of 5061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at single-nucleotide polymorphism (SNP) and gene levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13 × 10(-)(7)). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of genome-wide association study (GWAS) signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high-confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2 and PTPRD. Analyses at the gene level revealed association of IQCK and C16orf88 (both P<1 × 10(-)(6), experiment-wide significant), as well as OFCC1 (P=6.29 × 10(-)(5)). The suggestive findings in this study await replication in larger samples.
This review of challenging diagnostic issues concerning high-grade endometrial carcinomas is derived from the authors' review of the literature followed by discussions at the Endometrial Cancer ...Workshop sponsored by the International Society of Gynecological Pathologists in 2016. Recommendations presented are evidence-based, insofar as this is possible, given that the levels of evidence are weak or moderate due to small sample sizes and nonuniform diagnostic criteria used in many studies. High-grade endometrioid carcinomas include FIGO grade 3 endometrioid carcinomas, serous carcinomas, clear cell carcinomas, undifferentiated carcinomas, and carcinosarcomas. FIGO grade 3 endometrioid carcinoma is diagnosed when an endometrioid carcinoma exhibits >50% solid architecture (excluding squamous areas), or when an architecturally FIGO grade 2 endometrioid carcinoma exhibits marked cytologic atypia, provided that a glandular variant of serous carcinoma has been excluded. The most useful immunohistochemical studies to make the distinction between these 2 histotypes are p53, p16, DNA mismatch repair proteins, PTEN, and ARID1A. Endometrial clear cell carcinomas must display prototypical architectural and cytologic features for diagnosis. Immunohistochemical stains, including, Napsin A and p504s can be used as ancillary diagnostic tools; p53 expression is aberrant in a minority of clear cell carcinomas. Of note, clear cells are found in all types of high-grade endometrial carcinomas, leading to a tendency to overdiagnose clear cell carcinoma. Undifferentiated carcinoma (which when associated with a component of low-grade endometrioid carcinoma is termed "dedifferentiated carcinoma") is composed of sheets of monotonous, typically dyscohesive cells, which can have a rhabdoid appearance; they often exhibit limited expression of cytokeratins and epithelial membrane antigen, are usually negative for PAX8 and hormone receptors, lack membranous e-cadherin and commonly demonstrate loss of expression of DNA mismatch repair proteins and SWI-SNF chromatin remodeling proteins. Carcinosarcomas must show unequivocal morphologic evidence of malignant epithelial and mesenchymal differentiation.
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