The Implementation of Musculoskeletal Principles in a Clivus Chordoma Survivor with Neck Pain

Background: Long term side effects of cancer treatments can have a significant effect on functional mobility. Radiation therapy can have significant effects on all body tissue, including muscle and connective tissue. Surgical resection of malignant tumors also carries post-operative side effects that can influence function. The purpose of this case study is to highlight the successful treatment of neck pain despite limited treatment options from a complex past medical history. Case Description: This case study details the treatment of a 56-year-old female with a history of a clivus chordoma. Adverse effects following surgical resection, cervical fusion, and radiation therapy compelled this patient to present to an outpatient orthopedic clinic with complaints of neck pain and the presence of multiple functional deficits. Intervention: The intervention focused on manual therapy to address soft tissue adhesions in the upper quarter, therapeutic exercise to increase thoracic mobility, neuromuscular re-education of the transverse abdominus and diaphragm, and education for the successful integration of therapy principles to activities of daily living and exercise. Outcome Measures: The outcome measures utilized with this patient were limited to the Focus On Therapeutic Outcomes survey. Discussion: Several publications on the topic of clivus chordoma treatment, radiation therapy, and the overall neuromuscular complications experienced by cancer survivors acknowledge the role that physical therapy must play in the successful rehabilitation of these patients. Review of the related literature provides support for the interventions utilized in this case study including soft tissue mobilization, joint mobilization, therapeutic exercise, and neuromuscular re-education

Dosimetric evidence confirms computational model for magnetic field induced dose distortions of therapeutic proton beams

Given the sensitivity of proton therapy to anatomical variations, this cancer treatment modality is expected to benefit greatly from integration with magnetic resonance (MR) imaging. One of the obstacles hindering such an integration are strong magnetic field induced dose distortions. These have been predicted in simulation studies, but no experimental validation has been performed so far. Here we show the first measurement of planar distributions of dose deposited by therapeutic proton pencil beams traversing a one-Tesla transversal magnetic field while depositing energy in a tissue-like phantom using film dosimetry. The lateral beam deflection ranges from one millimeter to one centimeter for 80 to 180 MeV beams. Simulated and measured deflection agree within one millimeter for all studied energies. These results proof that the magnetic field induced proton beam deflection is both measurable and accurately predictable. This demonstrates the feasibility of accurate dose measurement and hence validates dose predictions for the framework of MR-integrated proton therapy

Determinisitic Writing and Control of the Dark Exciton Spin using Short Single Optical Pulses

We demonstrate that the quantum dot-confined dark exciton forms a long-lived integer spin solid state qubit which can be deterministically on-demand initiated in a pure state by one optical pulse. Moreover, we show that this qubit can be fully controlled using short optical pulses, which are several orders of magnitude shorter than the life and coherence times of the qubit. Our demonstrations do not require an externally applied magnetic field and they establish that the quantum dot-confined dark exciton forms an excellent solid state matter qubit with some advantages over the half-integer spin qubits such as the confined electron and hole, separately. Since quantum dots are semiconductor nanostructures that allow integration of electronic and photonic components, the dark exciton may have important implications on implementations of quantum technologies consisting of semiconductor qubits.Comment: Added two authors, minor edits to figure captions, expanded discussion of dark exciton eigenstate

Image Performance Characterization of an In-Beam Low-Field Magnetic Resonance Imaging System During Static Proton Beam Irradiation

Image guidance using in-beam real-time magnetic resonance (MR) imaging is expected to improve the targeting accuracy of proton therapy for moving tumors, by reducing treatment margins, detecting interfractional and intrafractional anatomical changes and enabling beam gating. The aim of this study is to quantitatively characterize the static magnetic field and image quality of a 0.22T open MR scanner that has been integrated with a static proton research beamline. The magnetic field and image quality studies are performed using high-precision magnetometry and standardized diagnostic image quality assessment protocols, respectively. The magnetic field homogeneity was found to be typical of the scanner used (98ppm). Operation of the beamline magnets changed the central resonance frequency and magnetic field homogeneity by a maximum of 16Hz and 3ppm, respectively. It was shown that the in-beam MR scanner features sufficient image quality and influences of simultaneous irradiation on the images are restricted to a small sequence-dependent image translation (0.1–0.7mm) and a minor reduction in signal-to-noise ratio (1.3%–5.6%). Nevertheless, specific measures have to be taken to minimize these effects in order to achieve accurate and reproducible imaging which is required for a future clinical application of MR integrated proton therapy

A Nickase Cas9 Gene-Drive System Promotes Super-Mendelian inheritance in Drosophila

CRISPR-based gene-drives have been proposed for managing insect populations, including disease-transmitting mosquitoes, due to their ability to bias their inheritance toward super-Mendelian rates (\u3e50%). Current technologies use a Cas9 that introduces DNA double-strand breaks into the opposing wild-type allele to replace it with a copy of the gene-drive allele via DNA homology-directed repair. However, the use of different Cas9 versions is unexplored, and alternative approaches could increase the available toolkit for gene-drive designs. Here, we report a gene-drive that relies on Cas9 nickases that generate staggered paired nicks in DNA to propagate the engineered gene-drive cassette. We show that generating 5\u27 overhangs in the system yields efficient allelic conversion. The nickase gene-drive arrangement produces large, stereotyped deletions that are advantageous to eliminate viable animals carrying small mutations when targeting essential genes. Our nickase approach should expand the repertoire for gene-drive arrangements aimed at applications in mosquitoes and beyond

Very Preterm Birth is Reduced in Women Receiving an Integrated Behavioral Intervention: A Randomized Controlled Trial

Background This study examines whether an integrated behavioral intervention with proven efficacy in reducing psycho-behavioral risks (smoking, environmental tobacco smoke exposure (ETSE), depression, and intimate partner violence (IPV)) in African-Americans is associated with improved pregnancy outcomes Methods A randomized controlled trial targeting risks during pregnancy was conducted in the District of Columbia. African-American women were recruited if reporting at least one of the risks mentioned above. Randomization to intervention or usual care was site and risk specific. Sociodemographic, health risk and pregnancy outcome data were collected. Data on 819 women, and their singleton live born infants were analyzed using an intent-to-treat approach. Bivariate analyses preceded a reduced logistical model approach to elucidate the effect of the intervention on the reduction of prematurity and low birth weight. Results The incidence of low birthweight LBW was 12% and very low birthweight VLBW was 1.6%. Multivariate logistic regression results showed that depression was associated with LBW (OR=1.71, 95%CI=1.12-2.62). IPV was associated with PTB and VPTB (OR 1.64, 95%CI=1.07-2.51, OR=2.94, 95%CI=1.40-6.16, respectively). The occurrence of VPTB was significantly reduced in the intervention compared to the usual care group (OR=0.42, 95%CI=0.19-0.93). Conclusions Our study confirms the significant associations between multiple psycho-behavioral risks and poor pregnancy outcomes, including LBW and PTB. Our behavioral intervention with demonstrated efficacy in addressing multiple risk factors simultaneously reduced VPTB within an urban minority population

Efficient allelic-drive in Drosophila.

Gene-drive systems developed in several organisms result in super-Mendelian inheritance of transgenic insertions. Here, we generalize this "active genetic" approach to preferentially transmit allelic variants (allelic-drive) resulting from only a single or a few nucleotide alterations. We test two configurations for allelic-drive: one, copy-cutting, in which a non-preferred allele is selectively targeted for Cas9/guide RNA (gRNA) cleavage, and a more general approach, copy-grafting, that permits selective inheritance of a desired allele located in close proximity to the gRNA cut site. We also characterize a phenomenon we refer to as lethal-mosaicism that dominantly eliminates NHEJ-induced mutations and favors inheritance of functional cleavage-resistant alleles. These two efficient allelic-drive methods, enhanced by lethal mosaicism and a trans-generational drive process we refer to as "shadow-drive", have broad practical applications in improving health and agriculture and greatly extend the active genetics toolbox

Sequential screening for psychosocial and behavioural risk during pregnancy in a population of urban African Americans

Objective: Screening for psychosocial and behavioral risks, such as depression, intimate partner violence and smoking, during pregnancy is considered state-of-the-art in prenatal care (PNC). This prospective longitudinal analysis examines the added benefit of repeated screening over a one-time screen in identifying such risks during pregnancy. Design: Data were collected as part of a randomized controlled trial to address intimate partner violence (IPV), depression, smoking and environmental tobacco smoke exposure (ETSE) in African-Americans women. Setting: PNC sites in the District of Columbia serving mainly minority women Population: 1044 African-American pregnant women in the District of Columbia Methods: Mothers were classified by their initial response (acknowledgement of risks) and updated during pregnancy. Risks were considered new if they were not previously reported. Standard hypothesis tests and logistic regression were used to predict acknowledgment of any new risk(s) during pregnancy. Main Outcome Measures: New risks; psychosocial variables to understand what factors might help identify acknowledgement of additional risk(s). Results: Repeated screening identified more mothers acknowledging risk over time. Reported smoking increased by 11%, ETSE by 19%, IPV by 9%, and depression by 20%. The psychosocial variables collected at the baseline that were entered into the logistic regression model included relationship status, education, Medicaid, illicit drug use, and alcohol use during pregnancy. Among these, only education less than high school was associated in acknowledgement of new risk in the bivariate analyses and significantly predicted identification of new risks (OR=1.39, 95%CI, 1.01-1.90). Conclusions: It is difficult early on to predict who will acknowledge new risks over the course of pregnancy, thus all women should be screened repeatedly to allow identification and intervention during PNC

An Intervention to Reduce Environmental Tobacco Smoke Exposure Improves Pregnancy Outcomes

Objective—We tested the efficacy of a cognitive-behavioral intervention in reducing environmental tobacco smoke exposure (ETSE) and improving pregnancy outcomes among African-American women. Methods—We recruited 1,044 women to a randomized controlled trial during 2001-2004 in Washington, DC. Data on 691 women with self-reported ETSE were analyzed. A subset of 520 ETSE women and salivary cotinine levels (SCLs)/ml was also analyzed. Individually tailored counseling sessions adapted from evidence-based interventions for ETSE and other risks, were delivered to the intervention group. The usual care group received routine prenatal care as determined by their provider. Logistic regression models were used to predict ETSE before delivery and adverse pregnancy outcomes. Results—Women in the intervention were less likely to self-report ETSE before delivery when controlling for other covariates (OR=0.50, 95%CI=0.35-0.71). Medicaid recipients were more likely to have ETSE (OR=1.97, 95%CI=1.31-2.96). With advancing maternal age, the likelihood of ETSE was less (OR=0.96, 95%CI=0.93-0.99). For women in the intervention the rates of very low birth weight (VLBW) and very preterm birth (VPTB) were significantly improved (OR=0.11, 95%CI=0.01-0.86; OR=0.22, 95%CI=0.07-0.68, respectively). For women with SCL/ml, maternal age was not significant. Intimate partner violence at baseline significantly increased the chances of VLBW and VPTB (OR=3.75, 95%CI=1.02-13.81; OR=2.71, 95%CI=1.11-6.62, respectively). These results were true for mothers who reported ETSE overall and for those with SCL/ml. Conclusions—This is the first randomized clinical trial demonstrating efficacy of a cognitivebehavioral intervention targeting ETSE in pregnancy. We significantly reduced ETSE as well as VPTB and VLBW, leading causes of neonatal mortality and morbidity in minority populations. This intervention may reduce health disparities seen in reproductive outcomes