Indirect induction of radiation lymphomas in mice. Evidence for a novel, transmissible leukemogen.

The transmission of a lymphomagenic agent(s) from the bone marrow of irradiated mice to thymic target cells has been demonstrated by: (a) the induction of T cell lymphomas in nonirradiated thymic grafts implanted in irradiated, Thy-l-congenic mice, (b) the induction of T cell lymphomas of host origin in mice infused with bone marrow from irradiated, Thy-l-congenic donors. The latter procedure also yields an appreciable number of pre-B cell lymphomas of uncertain origin. The results confirm Kaplan's theory that radiation induces thymic lymphomas in mice by an indirect mechanism. However, the previously described radiation leukemia virus is clearly not involved in the majority of transferred lymphomas. We propose that the mediating agent in radiation lymphomagenesis is a novel, transmissible agent induced in the bone marrow, but exerting its transforming activity on cells in the thymus. The nature and mode of action of the agent are under investigation

How did the discussion go: Discourse act classification in social media conversations

We propose a novel attention based hierarchical LSTM model to classify discourse act sequences in social media conversations, aimed at mining data from online discussion using textual meanings beyond sentence level. The very uniqueness of the task is the complete categorization of possible pragmatic roles in informal textual discussions, contrary to extraction of question-answers, stance detection or sarcasm identification which are very much role specific tasks. Early attempt was made on a Reddit discussion dataset. We train our model on the same data, and present test results on two different datasets, one from Reddit and one from Facebook. Our proposed model outperformed the previous one in terms of domain independence; without using platform-dependent structural features, our hierarchical LSTM with word relevance attention mechanism achieved F1-scores of 71\% and 66\% respectively to predict discourse roles of comments in Reddit and Facebook discussions. Efficiency of recurrent and convolutional architectures in order to learn discursive representation on the same task has been presented and analyzed, with different word and comment embedding schemes. Our attention mechanism enables us to inquire into relevance ordering of text segments according to their roles in discourse. We present a human annotator experiment to unveil important observations about modeling and data annotation. Equipped with our text-based discourse identification model, we inquire into how heterogeneous non-textual features like location, time, leaning of information etc. play their roles in charaterizing online discussions on Facebook

Prospective associations of low muscle mass and strength with health-related quality of life over 10-year in community-dwelling older adults

Aims: This study aims to describe the associations of low muscle mass, handgrip (HGS) and lower-limb muscle strength (LMS) with health-related quality of life (HRQoL) over 10 years in community-dwelling older adults.Methods: Participants (N = 1002; 51% women; mean age 63 ± 7.4 years) were prospectively followed for 10 years. HRQoL was measured using the validated assessment of quality of life (AQoL) instrument. Appendicular lean mass (ALM) was assessed using dual energy X-ray absorptiometry and normalized to body mass index (BMI). HGS and LMS were assessed using dynamometers. Low ALM/BMI (ALM/BMILOW), LMS (LMSLOW) and HGS (HGSLOW) at baseline were defined as the lowest 20% of the sex-specific distribution for each measure. Linear mixed effect regression models, adjusting for confounders, were used to estimate the association between ALM/BMILOW, LMSLOW, and HGSLOW at baseline and HRQoL over 10 years.Results: Participants with LMSLOW (β = -0.061, 95% CI: -0.089, -0.033) and women (β = -0.089, 95% CI: -0.129, -0.049) but not men (β = -0.023, 95% CI: -0.064, 0.019) with HGSLOW had clinically meaningful reductions in HRQoL over 10 years compared to those with normal strength. There was a weaker but statistically significant association between ALM/BMILOW and 10-year HRQoL (β = -0.038, 95% CI: -0.068, -0.008).Conclusions: Lower-limb muscle strength and handgrip strength (in women only), which can be easily measured in clinical practice, appear more important than muscle mass for HRQoL

Progress in HPV vaccination in low- and lower-middle-income countries.

The past 10 years have seen remarkable progress in the global scale-up of human papillomavirus (HPV) vaccinations. Forty-three low- and lower-middle-income countries (LLMICs) have gained experience in delivering this vaccine to young adolescent girls through pilot programs, demonstration programs, and national introductions and most of these have occurred in the last 4 years. The experience of Senegal is summarized as an illustrative country case study. Publication of numerous delivery experiences and lessons learned has demonstrated the acceptability and feasibility of HPV vaccinations in LLMICs. Four areas require dedicated action to overcome remaining challenges to national scaling-up: maintaining momentum politically, planning successfully, securing financing, and fostering sustainability. Advances in policy, programming, and science may help accelerate reaching 30 million girls in LLMICs with HPV vaccine by 2020

Branch facial nerve trauma after superficial temporal artery biopsy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Giant cell arteritis is an emergency requiring prompt diagnosis and treatment. Superficial temporal artery biopsy is the gold diagnostic standard. Complications are few and infrequent; however, facial nerve injury has been reported, leaving an untoward cosmetic outcome. This case report is to the best of our knowledge only the fourth one presented in the available literature so far regarding facial nerve injury from superficial temporal artery biopsy.</p> <p>Case presentation</p> <p>A 73-year-old Caucasian woman presented for neurological evaluation regarding eyebrow and facial asymmetry after a superficial temporal artery biopsy for presumptive giant cell arteritis-induced cephalalgia.</p> <p>Conclusion</p> <p>Damage to branches of the facial nerve may occur after superficial temporal artery biopsy, resulting in eyebrow droop. Although an uncommon and sparsely reported complication, all clinicians of various specialties involved in the care of these patients should be aware of this given the gravity of giant cell arteritis and the widespread use of temporal artery biopsy.</p

Modeling genome-wide replication kinetics reveals a mechanism for regulation of replication timing

We developed analytical models of DNA replication that include probabilistic initiation of origins, fork progression, passive replication, and asynchrony.We fit the model to budding yeast genome-wide microarray data probing the replication fraction and found that initiation times correlate with the precision of timing.We extracted intrinsic origin properties, such as potential origin efficiency and firing-time distribution, which cannot be done using phenomenological approaches.We propose that origin timing is controlled by stochastically activated initiators bound to origin sites rather than explicit time-measuring mechanisms

Mathematical modeling of the metastatic process

Mathematical modeling in cancer has been growing in popularity and impact since its inception in 1932. The first theoretical mathematical modeling in cancer research was focused on understanding tumor growth laws and has grown to include the competition between healthy and normal tissue, carcinogenesis, therapy and metastasis. It is the latter topic, metastasis, on which we will focus this short review, specifically discussing various computational and mathematical models of different portions of the metastatic process, including: the emergence of the metastatic phenotype, the timing and size distribution of metastases, the factors that influence the dormancy of micrometastases and patterns of spread from a given primary tumor.Comment: 24 pages, 6 figures, Revie

HIV Testing for Children in Resource-Limited Settings: What Are We Waiting For?

Scott Kellerman and Shaffiq Essajee argue that the time has come to increase access to HIV testing for children, especially in sub-Saharan Africa

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells