Search

Summary: The optimal therapeutic approach for relapsed/refractory (R/R) Waldenström's Macroglobulinaemia (WM) has not been clearly defined, especially after treatment with chemoimmunotherapy (CIT) and covalent Bruton's tyrosine kinase inhibitors (cBTKi). The PembroWM trial is a multi‐centre, phase II, single‐arm study assessing the safety, tolerability and efficacy of rituximab with pembrolizumab in R/R WM patients who had received at least one prior line of treatment, with all having relapsed post‐CIT and most also exposed to cBTKi. A total of 17 patients were enrolled, with a median age of 70, and median of three prior lines of therapy with 15 either refractory or intolerant of a cBTKi. A significant proportion was identified as genomically high risk with BTKC481, CXCR4 and MYD88 L265P wild‐type aberrations. Twenty‐four‐week overall response rate was 50% (60% CI 39.3%–60.7%), and median duration of response was 11.6 months (IQR: 6.3–17). The median progression‐free survival was 13.6 months (95% CI 3–19.8), and the median overall survival (OS) was not reached. Treatment was well tolerated, with minimal numbers of immune‐mediated AEs typically seen with checkpoint inhibitors. PembroWM is the first study to evaluate the feasibility of PD‐1 axis modulation in WM and has shown that in combination with Rituximab the combination is safe and deliverable. [ABSTRACT FROM AUTHOR]

This paper discusses how juvenile waiver policies may be leading to a reduction in the rehabilitative nature of the juvenile justice system. The first section discusses the value of the juvenile justice system. Here, the beginning of the juvenile justice system and why the juvenile justice system is important will be summarized. The second section explains the movement that is being made toward a more punitive approach in regard to juvenile delinquents and how this could lead to the erosion of the juvenile justice system. Next is a discussion of how waivers play a part in the erosion and how their continued use could prove very dangerous for the juvenile justice system. The next section will look at the implications of the erosion and what could potentially happen if we lost the juvenile system. Last, there will be a glance at possibilities for the future, along with suggestions on how to improve the use of waivers. Overall, this paper will show that the use of juvenile waivers may be leading the United States away from a rehabilitative system for juveniles to a smaller version of an adult criminal court. [ABSTRACT FROM AUTHOR]

Objective: Effective treatments for obsessive-compulsive disorder (OCD) exist, but additional treatment options are needed. The effectiveness of 8 sessions of acceptance and commitment therapy (ACT) for adult OCD was compared with progressive relaxation training (PRT). Method: Seventy-nine adults (61% female) diagnosed with OCD (mean age = 37 years; 89% Caucasian) participated in a randomized clinical trial of 8 sessions of ACT or PRT with no in-session exposure. The following assessments were completed at pretreatment, posttreatment, and 3-month follow-up by an assessor who was unaware of treatment conditions: Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Beck Depression Inventory-II, Quality of Life Scale, Acceptance and Action Questionnaire, Thought Action Fusion Scale, and Thought Control Questionnaire. Treatment Evaluation Inventory was completed at posttreatment. Results: ACT produced greater changes at posttreatment and follow-up over PRT on OCD severity (Y-BOCS: ACT pretreatment = 24.22, posttreatment = 12.76, follow-up = 11.79; PRT pretreatment = 25.4, posttreatment = 18.67, follow-up = 16.23) and produced greater change on depression among those reporting at least mild depression before treatment. Clinically significant change in OCD severity occurred more in the ACT condition than PRT (clinical response rates: ACT posttreatment = 46%-56%, follow-up = 46%-66%; PRT posttreatment = 13%-18%, follow-up = 16%-18%). Quality of life improved in both conditions but was marginally in favor of ACT at posttreatment. Treatment refusal (2.4% ACT, 7.8% PRT) and dropout (9.8% ACT, 13.2% PRT) were low in both conditions. Conclusions: ACT is worth exploring as a treatment for OCD. (Contains 1 table, 2 figures and 1 footnote.)

Atlantic Goliath Grouper, Epinephelus itajara, the largest grouper in the western North Atlantic, exhibits life history characteristics (e.g., it is slow-growing, long-lived, and late-maturing) that make it particularly susceptible to fishing pressure. Otoliths, the structure typically processed for age determination, are usually collected as part of fishery monitoring, but otoliths are not available from Goliath Grouper due to a harvest moratorium enacted in 1990 for United States waters. Alternative structures—such as dorsal fin rays or spines—can be acquired for ageing via nonlethal sampling and may provide reliable age estimates. Since 2006, the Florida Fish and Wildlife Conservation Commission (FWC) has been collecting incidental Goliath Grouper samples from mortality events including those from cold kills and red tides. Corresponding otolith, dorsal fin ray and dorsal fin spine samples were compared to determine the accuracy and precision of the external ageing structures. Marginal increment analyses indicated that annulus (translucent zone) deposition occurred primarily in March–June on spines and in April–June on rays. While ages determined from both rays and spines exhibited high precision, the accuracy compared to otolith ages was low as a result of systematic underageing of both external structures, particularly at the oldest age classes. A correction factor was applied to rays and spines that remedied the underageing, but the correction factor was more successful for spines. An analysis of ray and spine section accuracy based on nonlethal structure removal from the fish (i.e., comparing ages from sections at the base of the structure within the body to those sectioned from the external surface of the body) determined that spines can be accurately aged when sampled distal of the base of the structure, but that rays cannot. Nonlethal sampling and ageing of Goliath Grouper spines facilitated by public participation could address management goals and help determine the offshore population age structure. Simultaneously, it could contribute critical data needed for a traditional stock assessment, should such a path be warranted by the recovery or management of the species. [ABSTRACT FROM AUTHOR]

The Hogfish Lachnolaimus maximus is a high‐value food fish with significant recreational and commercial fishing pressure and is a candidate species for marine aquaculture. There is a need to define safe and effective methods of anesthesia for handling of this species for aquaculture. Anesthesia efficacy was assessed with wild‐collected adult (>20 cm; 0.2–1.2 kg) and juvenile F1 (<11 cm; 5–50 g) Hogfish by using tricaine methanesulfonate (Tricaine‐S) at 25, 50, 100, 125, and 150 mg/L and AQUI‐S 20E (10% eugenol) at 50, 75, 100, 200, 300, 400, and 500 mg/L to determine favorable doses for minor handling. Favorable doses resulted in induction of light anesthesia and recovery times each under 5 min, zero mortality, and limited excitation behavior. For adult Hogfish, Tricaine‐S was effective at inducing light anesthesia at 100–150 mg/L and was preferred over the effective range of AQUI‐S 20E doses (100–200 mg/L) based on fish behavioral observations while undergoing anesthesia. Additionally, induction of deep anesthesia was explored to inform potential doses for major and potentially lethal procedures. These same ranges were effective at inducing deep anesthesia in adults. Juvenile fish were effectively anesthetized at the same doses of Tricaine‐S (100–150 mg/L) and were induced to light and deep anesthesia faster than adults at the same dose levels. AQUI‐S 20E was effective at inducing light anesthesia in juveniles at all levels tested; however, no favorable dose for deep anesthesia was found. Overall, Hogfish were anesthetized with Tricaine‐S at similar doses used with other species and responded to AQUI‐S 20E similarly in terms of efficacy but unfavorably in terms of behavior. [ABSTRACT FROM AUTHOR]

The article discusses the Great Goliath Grouper Count (GGGC), a program initiated in 2010 by Florida Sea Grant and the Florida Fish and Wildlife Conservation Commission (FWC) to collect data on the Atlantic goliath grouper. The goliath grouper is a large reef species that was overfished and experienced population declines in the past. The GGGC utilizes trained divers who follow standardized protocols to report data on the number, size, and location of goliath groupers observed during underwater surveys. The program has expanded to include the entire state of Florida and has provided valuable data for stock assessments and fisheries management. [Extracted from the article]

Specialized domestic violence courts are presumed to be more effective than general case processing in understanding and addressing the unique issues associated with this crime type, which should lead to reduced recidivism among offenders. Research, however, is less clear about whether and how domestic violence courts reduce recidivism. This study analyzes data from a misdemeanor, expedited domestic violence court in southeast Texas to assess whether defendant characteristics and court processing characteristics influence recidivism among offenders processed through the specialty docket. Results indicate that case processing time was a significant predictor of rearrest for domestic violence. Offenders who had a prior domestic violence arrest were twice as likely to have a subsequent domestic violence arrest. Offenders who received a jail sentence were significantly more likely to have a subsequent domestic violence arrest. Policy implications and future research needs are also discussed. [ABSTRACT FROM AUTHOR]

We report the case of a previously healthy 49-year-old woman who presented with upper gastrointestinal bleeding, which was found at laparotomy to be due to high-grade B cell gastric lymphoma. CT scans showed that this was partially adherent to the spleen, with erosion of the gastric wall and suggested impending perforation. Given the risk of perforation, further surgical intervention (gastrectomy and splenectomy) was considered; however, after multidisciplinary team discussion, we chose to offer chemotherapy and careful inpatient observation instead. Our patient made a full recovery with no perforation. The message from our experience and literature review is that medical management may lead to a more favourable outcome in gastric lymphoma than surgery, despite radiological appearances suggesting impending perforation. This approach avoids the risk of the lymphoma progressing at other anatomical sites secondary to delays in giving chemotherapy. If this approach is followed, the patient must be carefully monitored. [ABSTRACT FROM AUTHOR]

Objective: There is little data defining safe transport protocols for spica-casted children. A single earlier study demonstrated the presence of a body cast alters kinematics and injury metrics during simulated side-impact crashes. Since then, the National Highway Transportation Safety Administration (NHTSA) proposed a new side-impact test protocol for evaluating child restraints. This test is more severe than the earlier tests, as it simulates an impact with a door intruding into the occupant space. As no currently available child restraint system (CRS) able to accommodate a spica-casted child has been evaluated using these updated testing criteria, the objective of this study was to evaluate current restraint options in simulated side-impact collisions using an anthropomorphic test device (ATD) modeled after a 3-year-old.Methods: Four commercially available CRSs able to accommodate a spica-casted Q3s side-impact ATD were selected for testing. Side-impact testing was performed using casted and uncasted ATDs in compliance with the NHTSA proposed side-impact test. High-speed photography and ATD instrumentation were used to measure selected injury criteria.Results: HIC15 values were highest in CRSs with less robust side wings, such as the Merritt WallenburgTM (HIC15 = 1,373), which allow for the occupant to interact with the intruding door panel. Head contact with the door panel was found to correspond with high resultant neck peak force. Pelvic acceleration magnitudes were greatest for the uncasted tests. Casted tests with a CRS that included an armrest were associated with greater torso rotation in the frontal plane with the left shoulder moving toward the door panel.Conclusions: The presence of a spica cast alters injury metrics in side-impact testing. Spica specific child safety seats are not yet optimized for side-impact with door intrusion. This is due to a lack of adequate side cushion wings, which may place both casted and uncasted occupants at increased likelihood for injury through head contact with an intruding door. Additional work is needed to improve the safety of CRSs for both casted and uncasted children in side-impact collisions. [ABSTRACT FROM AUTHOR]

Hogfish (Lachnolaimus maximus), a large wrasse native to the western Atlantic, are a popular sport and food fish whose southern population have been experiencing overfishing for the past 30 years. Despite their popularity, interest in commercial culture has only recently emerged. Poorly defined culture methods persist as an impediment to potential restoration efforts with this species. Additionally, no information currently exists on effective marking procedures for hatchery produced hogfish. Feasibility of culture and potential stock enhancement is predicated on elucidation of effective protocols. To this end, we explored the efficacy of various protocols using Calcein as a marking agent for hogfish. Calcein is a non-lethal, fluorescent, chemical marker that binds to the calcified structures in exposed animals. To assess its potential for use on hogfish, we used the osmotic induction method where animals were exposed to a hypersaline environment for 3.5 minutes prior to immersion in calcein for the same time, thereby resulting in calcein uptake and marking. We tested pre-treatment salinities of 32. 45, 60, and 75 g/L followed by a 3 g/L calcein exposure. A second experiment then tested calcein concentrations of 0, 1, 3, and 5 g/L using the salinity pretreatment that resulted in the brightest mark from the first experiment: only the highest saline and calcein concentrations showed significantly brighter marks than the weakest marked fish. These results identify baseline calcein marking protocols for use with hogfish. Further research into mark retention is warranted to evaluate the usefulness of this tool in potential stock enhancements efforts. [ABSTRACT FROM AUTHOR]

This paper uses integrated theory to explain gang fighting. Integrated theory combines elements of social control, social learning, and strain theories. We focus on gang fighting to assess the generality of integrated theory because it constitutes serious violent collective behavior which is linked to other problem behaviors. Few explanations for such behavior are offered. We examine the relationship between integrated theory and gang fighting using multi-level modeling and data from the first five waves of the National Youth Survey Family Study for the period 1976-1980. Support for direct effects of some components of integrated theory was found, including normlessness, delinquent peer-group bonding, and grades in school. [ABSTRACT FROM AUTHOR]

Nurse sharks have not previously been known to migrate. Nurse sharks of the Dry Tortugas (DRTO) mating population have a highly predictable periodic residency cycle, returning to the Dry Tortugas Courtship and Mating Ground (DTCMG) annually (males) or bi- to triennially (females) during the June/July mating season. For 23 years we have followed the movements of 76 recaptured adults of a total of 115 tagged adults. Telemetry detections of 40 females tagged with acoustic transmitters show that most tagged and presumably post-partum females are continuously present in the DRTO in the fall, winter and early spring following the June mating season but these females depart in late March to early May. Detections reveal these females avoid the DTCMG completely during the next mating season, returning from late summer to fall. Telemetry records of nine of 17 adult males that co-habited with these females in the DTCMG depart DRTO waters every July. Both sexes may overwinter in the DRTO. Between 2011 and 2016 three males and five females with transmitters were detected to move up the west coast of Florida outside of the mating season as far north as the waters off Tampa Bay (335 km). Six others were only detected in the lower Florida Keys (292 km). Nine sharks returned to DRTO; one returned six times. Some overwintered and some resumed courtship in June, demonstrating both resident and migratory contingents within their population, partial migration and an ability to navigate with high spatial and temporal precision. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis, the causative agent of tuberculosis, is a major cause of morbidity and mortality worldwide. However, an effective vaccine for M. tuberculosis is lacking. We panned a phage display library using monoclonal antibodies against M. tuberculosis liporabinomannan (LAM), an important component of the M. tuberculosis cell wall, and identified two peptide sequences, HSFKWLDSPRLR or SGVYKVAYDWQH, with high antibody affinity after multiple rounds of panning. Only the HSFKWLDSPRLR peptide induced an anti-LAM response when conjugated to either keyhole limpet hemocyanin (KLH) or to the baculovirus Autographa californica multicapsid nucleopolyherovirus (AcMNPV) when introduced into mice by injection or via intranasal inoculation, respectively. Vaccination with AcMNPV conjugated HSFKWLDSPRLR peptide delayed mortality in a mouse model of tuberculosis. Thus, we report a proof of principle M. tuberculosis vaccination strategy combining an anti-LAM mimotope with a baculovirus delivery system. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis, the causative agent of tuberculosis, is responsible for 1.5 million deaths annually. We previously showed that M. tuberculosis infection in mice induces expression of the CO-producing enzyme heme oxygenase (HO1) and that CO is sensed by M. tuberculosis to initiate a dormancy program. Further, mice deficient in HO1 succumb to M. tuberculosis infection more readily than do wild-type mice. Although mouse macrophages control intracellular M. tuberculosis infection through several mechanisms, such as NO synthase, the respiratory burst, acidification, and autophagy, how human macrophages control M. tuberculosis infection remains less well understood. In this article, we show that M. tuberculosis induces and colocalizes with HO1 in both mouse and human tuberculosis lesions in vivo, and that M. tuberculosis induces and colocalizes with HO1 during primary human macrophage infection in vitro. Surprisingly, we find that chemical inhibition of HO1 both reduces inflammatory cytokine production by human macrophages and restricts intracellular growth of mycobacteria. Thus, induction of HO1 by M. tuberculosis infection may be a mycobacterial virulence mechanism to enhance inflammation and bacterial growth. [ABSTRACT FROM AUTHOR]