Investigating the clinical advantages of a robotic linac equipped with a multileaf collimator in the treatment of brain and prostate cancer patients.

The purpose of this study was to evaluate the performance of a commercially available CyberKnife system with a multileaf collimator (CK-MLC) for stereotactic body radiotherapy (SBRT) and standard fractionated intensity-modulated radiotherapy (IMRT) applications. Ten prostate and ten intracranial cases were planned for the CK-MLC. Half of these cases were compared with clinically approved SBRT plans generated for the CyberKnife with circular collimators, and the other half were compared with clinically approved standard fractionated IMRT plans generated for conventional linacs. The plans were compared on target coverage, conformity, homogeneity, dose to organs at risk (OAR), low dose to the surrounding tissue, total monitor units (MU), and treatment time. CK-MLC plans generated for the SBRT cases achieved more homogeneous dose to the target than the CK plans with the circular collimators, for equivalent coverage, conformity, and dose to OARs. Total monitor units were reduced by 40% to 70% and treatment time was reduced by half. The CK-MLC plans generated for the standard fractionated cases achieved prescription isodose lines between 86% and 93%, which was 2%-3% below the plans generated for conventional linacs. Compared to standard IMRT plans, the total MU were up to three times greater for the prostate (whole pelvis) plans and up to 1.4 times greater for the intracranial plans. Average treatment time was 25 min for the whole pelvis plans and 19 min for the intracranial cases. The CK-MLC system provides significant improvements in treatment time and target homogeneity compared to the CK system with circular collimators, while maintaining high conformity and dose sparing to critical organs. Standard fractionated plans for large target volumes (>100 cm3) were generated that achieved high prescription isodose levels. The CK-MLC system provides more efficient SRS and SBRT treatments and, in select clinical cases, might be a potential alternative for standard fractionated treatments. PACS numbers: 87.56.nk, 87.56.bd

Genetic Modification Strategies to Enhance CAR T Cell Persistence for Patients With Solid Tumors

Immunotherapy with chimeric antigen receptor (CAR) T cells offers a promising method to improve cure rates and decrease morbidities for patients with cancer. In this regard, CD19-specific CAR T cell therapies have achieved dramatic objective responses for a high percent of patients with CD19-positive leukemia or lymphoma. Most patients with solid tumors however, have experienced transient or no benefit from CAR T cell therapies. Novel strategies are therefore needed to improve CAR T cell function for patients with solid tumors. One obstacle for the field is limited CAR T cell persistence after infusion into patients. In this review we highlight genetic engineering strategies to improve CAR T cell persistence for enhancing antitumor activity for patients with solid tumors

Safety of overlapping inpatient orthopaedic surgery: A multicenter study

BackgroundAlthough overlapping surgery is used to maximize efficiency, more empirical data are needed to guide patient safety. We conducted a retrospective cohort study to evaluate the safety of overlapping inpatient orthopaedic surgery, as judged by the occurrence of perioperative complications.MethodsAll inpatient orthopaedic surgical procedures performed at 5 academic institutions from January 1, 2015, to December 31, 2015, were included. Overlapping surgery was defined as 2 skin incisions open simultaneously for 1 surgeon. In comparing patients who underwent overlapping surgery with those who underwent non-overlapping surgery, the primary outcome was the occurrence of a perioperative complication within 30 days of the surgical procedure, and secondary outcomes included all-cause 30-day readmission, length of stay, and mortality. To determine if there was an association between overlapping surgery and a perioperative complication, we tested for non-inferiority of overlapping surgery, assuming a null hypothesis of an increased risk of 50%. We used an inverse probability of treatment weighted regression model adjusted for institution, procedure type, demographic characteristics (age, sex, race, comorbidities), admission type, admission severity of illness, and clustering by surgeon.ResultsAmong 14,135 cases, the frequency of overlapping surgery was 40%. The frequencies of perioperative complications were 1% in the overlapping surgery group and 2% in the non-overlapping surgery group. The overlapping surgery group was non-inferior to the non-overlapping surgery group (odds ratio [OR], 0.61 [90% confidence interval (CI), 0.45 to 0.83]; p < 0.001), with reduced odds of perioperative complications (OR, 0.61 [95% CI, 0.43 to 0.88]; p = 0.009). For secondary outcomes, there was a significantly lower chance of all-cause 30-day readmission in the overlapping surgery group (OR, 0.67 [95% CI, 0.52 to 0.87]; p = 0.003) and shorter length of stay (e, 0.94 [95% CI, 0.89 to 0.99]; p = 0.012). There was no difference in mortality.ConclusionsOur results suggest that overlapping inpatient orthopaedic surgery does not introduce additional perioperative risk for the complications that we evaluated. The suitability of this practice should be determined by individual surgeons on a case-by-case basis with appropriate informed consent.Level of evidenceTherapeutic Level III. See Instructions for Authors for a complete description of levels of evidence

Phase I study of dose escalation to dominant intraprostatic lesions using high-dose-rate brachytherapy.

PurposeRadiation dose escalation for prostate cancer improves biochemical control but is limited by toxicity. Magnetic resonance spectroscopic imaging (MRSI) can define dominant intraprostatic lesions (DIL). This phase I study evaluated dose escalation to MRSI-defined DIL using high-dose-rate (HDR) brachytherapy.Material and methodsEnrollment was closed early due to low accrual. Ten patients with prostate cancer (T2a-3b, Gleason 6-9, PSA < 20) underwent pre-treatment MRSI, and eight patients had one to three DIL identified. The eight enrolled patients received external beam radiation therapy to 45 Gy and HDR brachytherapy boost to the prostate of 19 Gy in 2 fractions. MRSI images were registered to planning CT images and DIL dose-escalated up to 150% of prescription dose while maintaining normal tissue constraints. The primary endpoint was genitourinary (GU) toxicity.ResultsThe median total DIL volume was 1.31 ml (range, 0.67-6.33 ml). Median DIL boost was 130% of prescription dose (range, 110-150%). Median urethra V120 was 0.15 ml (range, 0-0.4 ml) and median rectum V75 was 0.74 ml (range, 0.1-1.0 ml). Three patients had acute grade 2 GU toxicity, and two patients had late grade 2 GU toxicity. No patients had grade 2 or higher gastrointestinal toxicity, and no grade 3 or higher toxicities were noted. There were no biochemical failures with median follow-up of 4.9 years (range, 2-8.5 years).ConclusionsDose escalation to MRSI-defined DIL is feasible. Toxicity was low but incompletely assessed due to limited patients' enrollment

Past carbonate preservation events in the deep Southeast Atlantic Ocean (Cape Basin) and their implications for Atlantic overturning dynamics and marine carbon cycling

Micropaleontological and geochemical analyses reveal distinct millennial-scale increases in carbonate preservation in the deep Southeast Atlantic (Cape Basin) during strong and prolonged Greenland interstadials that are superimposed on long-term (orbital-scale) changes in carbonate burial. These data suggest carbonate oversaturation of the deep Atlantic and a strengthened Atlantic Meridional Overturning Circulation (AMOC) during the most intense Greenland interstadials. However, proxy evidence from outside the Cape Basin indicate that AMOC changes also occurred during weaker and shorter Greenland interstadials. Here we revisit the link between AMOC dynamics and carbonate saturation in the deep Cape Basin over the last 400 kyr (sediment cores TN057-21, TN057-10 and ODP Site 1089) by reconstructing centennial changes in carbonate preservation using mm-scale X-ray fluorescence (XRF) scanning data. We observe close agreement between variations in XRF Ca/Ti, sedimentary carbonate content and foraminiferal shell fragmentation, reflecting a common control primarily through changing deep-water carbonate saturation. We suggest that the high-frequency (sub-orbital) component of the XRF Ca/Ti records indicates the fast and recurrent redistribution of carbonate ions in the Atlantic basin via the AMOC during both long/strong- and short/weak North Atlantic climate anomalies. In contrast, the low- frequency (orbital) XRF Ca/Ti component is interpreted to reflect slow adjustments through carbonate compensation, and/or changes in the deep-ocean respired carbon content. Our findings emphasize the recurrent influence of rapid AMOC variations on the marine carbonate system during past glacial periods, providing a mechanism for transferring the impacts of North Atlantic climate anomalies to the global carbon cycle via the Southern Ocean.J.G. acknowledges support from the Swiss National Science Foundation (grant 200021_163003), the German Research Foundation (grant GO 2294/2-1) and the Gates Cambridge Trust. L.C.S. acknowledges the Royal Society, the Cambridge Isaac Newton Trust and NERC grant NE/J010545/1. S.L.J was funded by the Swiss National Science Foundation (grants PP00P2-144811 and PP002_172915)

‘Bell’ Pear

‘Bell’ (Pyrus communis L.) is an early-season pear variety that combines fire blight resistance with exceptional flavor and high productivity. Fire blight, caused by the bacterial pathogen Erwinia amylovora, is a devastating disease for pear growers in the mid-Atlantic region and other pear production areas prone to hot and humid climates. ‘Bell’ has exhibited strong resistance to natural infection by Erwinia compared with the susceptible, industry-standard ‘Bartlett’. ‘Bell’ also exhibits a “balanced” sugar and acidity content that is desirable and preferred by pear consumers. The US Department of Agriculture and Pennsylvania State University released ‘Bell’ in 2022 as a fresh-market pear for commercial, direct-to-market, and home production

Pathogen-reactive T helper cell analysis in the pig

There is growing interest in studying host-pathogen interactions in human-relevant large animal models such as the pig. Despite the progress in developing immunological reagents for porcine T cell research, there is an urgent need to directly assess pathogen-specific T cells-an extremely rare population of cells, but of upmost importance in orchestrating the host immune response to a given pathogen. Here, we established that the activation marker CD154 (CD40L), known from human and mouse studies, identifies also porcine antigen-reactive CD4(+) T lymphocytes. CD154 expression was upregulated early after antigen encounter and CD4(+)CD154(+) antigen-reactive T cells coexpressed cytokines. Antigen-induced expansion and autologous restimulation enabled a time-and dose-resolved analysis of CD154 regulation and a significantly increased resolution in phenotypic profiling of antigen-responsive cells. CD154 expression identified T cells responding to staphylococcal Enterotoxin B superantigen stimulation as well as T cells responding to the fungus Candida albicans and T cells specific for a highly prevalent intestinal parasite, the nematode Ascaris suum during acute and trickle infection. Antigen-reactive T cells were further detected after immunization of pigs with a single recombinant bacterial antigen of Streptococcus suis only. Thus, our study offers new ways to study antigen-specific T lymphocytes in the pig and their contribution to host-pathogen interactions

Volume 11

Table of Contents: Introduction, Dr. Roger A. Byrne, Dean From the Editor, Dr. Larissa Kat Tracy From the Designers, Rachel English, Rachel Hanson Synthesis of 3,5-substituted Parabens and their Antimicrobial Properties, Jacob Coarney, Ryan White Chernobyl: Putting Perestroika and Glasnot to the Test, Joseph Hyman Art by Jenny Raven Watering Down Accessibility: The Issue with Public Access to Alaska\u27s Federal Waterways, Meagan Garrett Why Has the Democratic Republic of the Congo outsourced its Responsibility to Educate its Citizens? Ibrahim Kante Art by Summer Meinhard A Computational Study of Single Molecule Diodes, Lauren Johnson Satire of the State through Discourse: Applying Althusser and Bakhtin, William Dean Howells Editha , Glen Spencer Design by Laura Gottschalk Why did the United Kingdom Vote to Leave the European Union?, Christopher Siefke Art by Pink Powell Art by Natasha Woodmany Method of Detection of PFOA in Water Samples, Katharine Colley Art by Abbey Mays The Rhetorical Construction of eSports\u27 Legitimacy, Charlotte Pott

Understanding the "Family Gap" in Pay for Women with Children

As the gender gap in pay between women and men has been narrowing, the "family gap" in pay between mothers and nonmothers has been widening. One reason may be the institutional structure in the United States, which has emphasized equal pay and opportunity policies but not family policies, in contrast to other countries that have implemented both. The authors now have evidence on the links between one such family policy and women's pay. Recent research suggests that maternity leave coverage, by raising women's retention after childbirth, also raises women's levels of work experience, job tenure, and pay

The Importance of an Early Onset of Migraine Preventive Disease Control: A Roundtable Discussion

Background: Newly approved migraine preventive therapies have allowed for rapid control of migraine activity, offering potential to minimize the burden of migraine. This report summarizes a roundtable discussion convened to analyze evidence for early onset of prevention, ascertain its clinical relevance, and provide guidance for healthcare professionals in crafting goals and treatment expectations for patients with migraine initiating preventive therapy. Methods: A virtual roundtable meeting of migraine clinicians, researchers, and patient advocates convened in October 2020. Participants reviewed and discussed data summarizing patient and healthcare professional perceptions of migraine prevention and evidence from the peer-reviewed and gray literature to develop corresponding recommendations. Summary: Evidence from clinical studies of anti-calcitonin gene-related peptide monoclonal antibodies (erenumab, fremanezumab, galcanezumab, and eptinezumab) and the chemodenervation agent onabotulinumtoxinA indicate that patients may experience reduction of migraine activity within 7 days of drug administration and early attainment of disease control is associated with improvements in clinically important outcomes. The roundtable of experts proposes that early onset be defined as demonstration of preventive benefits within 1 week of treatment initiation. We recommend focusing discussion with patients around “disease control” and potential benefits of early onset of prevention, so patients can set realistic preventive therapy goals and expectations