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Recent evidence implicates intensive panic control treatment (IPCT) - a full panic control treatment protocol compressed into a single weekend - as a viable alternative for Veterans with panic disorder who are unable or unwilling to commit to standard weekly cognitive behavioral therapy (CBT). However, no studies to date have examined pretreatment predictors of response to IPCT. Knowledge of such predictors may be important for understanding which Veterans are best suited for IPCT relative to standard CBT.Participants were military Veterans with a primary diagnosis of panic disorder (N = 26) who participated in three open trials of IPCT. Pretreatment predictors were tested within linear regression models used to predict panic disorder severity at 2-week and 6-month follow-up assessments. Pretreatment predictors included: Panic disorder severity, agoraphobic avoidance, PTSD symptoms, anxiety sensitivity, and age.Pretreatment symptoms of PTSD predicted reduced treatment response at 2-week but not 6-month follow-up, whereas pretreatment anxiety sensitivity predicted reduced response at 6-month but not 2-week follow-up.Current findings are tempered by the exploratory nature of the analyses and a small sample.Our study offers tentative evidence that success in IPCT may be linked to a distinct pretreatment profile relative to that of standard weekly therapy. These preliminary findings should be confirmed in larger studies that directly compare pretreatment predictors of intensive versus standard weekly CBT for panic disorder.

SIR is a recognised tool for establishing electrochemical reliability of electronic assemblies. Currently the test patterns in the standards reflect coarse pitch components. An intercomparison has been completed with the aim of establishing the introduction of a fine pitch SIR pattern with a 200µm gap. This exercise included the contribution from seven international participants. This new pattern moves the test method forward into the realm of current technologies where components of this pitch are common place. The study reported here validates the basis for the introduction of the new pattern, and confirms acceptable Gauge R&R for the SIR technique. The analysis also highlights the challenges in controlling humidity to achieve comparable results between different users. The results also point to the challenges in achieving acceptable Gauge R&R when measuring resistances >1011Ω.

Treatment dropout has been problematic with evidence-based treatments for posttraumatic stress disorder (PTSD), including cognitive processing therapy (CPT). This study sought to evaluate whether CPT group contributed to symptom improvement among treatment completers and non-completers.Sixty-one Iraq and Afghanistan combat Veterans self-selected CPT group or treatment as usual (TAU) forming a convenience sample. Defining treatment completion as attending at least nine sessions: 18 completed treatment, 20 dropped-out (DOs); 20 completed TAU, 3 lost to TAU follow-up.Multiple Regression revealed significant pre-post-treatment improvement, the Clinician-Administered PTSD Scale (CAPS-IV, F(5, 40.1) = 2.53, p = 0.0436). Reviewing DOs' last available PTSD Checklist-Military Version scores before leaving treatment, six achieved clinically significant improvement of10 points; seven a clinically reliable change of 5-10 points.These findings highlight that CPT group may be effective at reducing trauma-related symptoms among treatment completers and dropouts and point to the utility of a clinical definition of good treatment end-state.

Fear conditioning represents the prevailing model by which organisms acquire novel threat contingencies. However, little work has been devoted to linking laboratory measures of fear conditioning to the development of real-world threat responses. To fill this gap, the present study explored whether individual differences in a laboratory-based fear conditioning measure could predict levels of COVID-19-related anxiety and avoidance assessed during the first month of the pandemic.Forty-eight undergraduate students who had previously participated in two fear conditioning experiments prior to COVID-19 completed a survey assessing COVID-19 anxiety and avoidance. The fear conditioning experiment involved learning to discriminate between a shape contingently associated with mild electric shock (CS+) and two other shapes that were not (CS-).Increased subjective anxiety to our laboratory CS+ prior to the pandemic predicted heightened COVID-19 anxiety. Follow-up analyses revealed that participants with high COVID-19 anxiety exhibited increased anxiety to CS+ during the final experimental block relative to participants with low COVID-19 anxiety.Findings from this exploratory study tentatively implicate fear conditioning in the development of real-world fear responses and underscore the importance of investigating laboratory fear conditioning as a predictor of anxiety responses to real-world threats.

Fear overgeneralization is a potential pathogenic mechanism of anxiety-related disorders. A dominant model posits that overgeneralization occurs when the hippocampus fails to distinctly encode benign stimuli with insufficient similarity to previously encountered fear cues, triggering excessive retrieval of stored fear representations. This model has cross-species support but has not been causally tested in humans. A developing literature demonstrates that hippocampal network targeted transcranial magnetic stimulation (HNT-TMS) can strengthen hippocampal-dependent memory encoding. Building on this literature, we hypothesized that HNT-TMS would strengthen encoding of perceptually similar stimuli and thereby reduce retrieval errors (i.e., sharpen discrimination) in participants with post-traumatic stress symptoms. We predicted that this effect would emerge for fear stimuli as measured by the Farmer Task and neutral stimuli as measured by the Mnemonic Similarity Task. Continuous theta-burst stimulation (cTBS) was delivered to individualized left posterior-parietal targets derived via precision functional mapping, seed-based connectivity, and electric-field modeling methods. A vertex control target was also stimulated in a within-subject design (final N = 25). Multilevel models did not reveal significant interactions between stimulation target and fear or neutral stimulus discrimination. However, HNT-TMS strengthened fear discrimination in participants with lower sensitization, indexed by responsivity to a control stimulus perceptually unrelated to the CS+. Sensitization reflects indiscriminate fear responding unrelated to CS + similarity and is not expected to engage the hippocampal CS + matching function. Our findings therefore indicate that HNT-TMS may selectively sharpen fear discrimination when the hippocampal CS + matching function is more strongly engaged.

Insomnia is a common and impairing consequence of military deployment, but little is known about pre-deployment risk factors for post-deployment insomnia. Abnormal threat learning tendencies are commonly observed in individuals with insomnia and maladaptive responses to stress have been implicated in the development of insomnia, suggesting that threat learning could be an important risk factor for post-deployment insomnia. Here, we examined pre-deployment threat learning as a predictor of post-deployment insomnia and the potential mechanisms underlying this effect. Male servicemembers (N = 814) completed measures of insomnia, psychiatric symptoms, and a threat learning task before and after military deployment. Threat learning indices that differentiated participants with versus withoutinsomnia at post-deployment were tested as pre-deployment predictors of post-deployment insomnia. Post-deployment insomnia was linked to elevations on several threat learning indices at post-deployment, but only higher threat conditioning, as indexed by higher threat expectancy ratings to the danger cue, emerged as a pre-deployment predictor of post-deployment insomnia. This effect was independent of combat exposure levels and partially mediated by greater post-deployment nightmares. The tendency to acquire stronger expectations of aversive events following encounters with danger cues may increase risk for post-deployment insomnia, in part due to the development of more severe nightmares.

Previous research has implicated reductions in anxiety sensitivity (AS) - the dispositional tendency to fear anxiety-related sensations - as critical to change during cognitive behavioral therapy (CBT) for anxiety. However, the relationship of AS to anxiety symptom remittance following CBT remains largely unknown. To address this gap, the current study evaluated prospective associations between AS and symptoms of various anxiety disorders following completion of the Coordinated Anxiety Learning and Management (CALM) study- a large clinical trial evaluating the efficacy of a brief, computer-facilitated CBT intervention for transdiagnostic anxiety within primary care. Participants were randomized to CALM (n = 460) or a control treatment (n = 501) and completed self-report measures of general and disorder-specific anxiety symptoms at pretreatment and at 6-month, 12-month, and 18-month follow-up. Longitudinal relations between AS and each anxiety measure across timepoints and within each treatment group were assessed using cross-lagged panel models. Results indicated that higher AS following CALM predicted greater anxiety symptoms at the subsequent timepoint for all anxiety symptoms except social anxiety symptoms. Higher anxiety following treatment also predicted later AS. These findings implicate AS as an indicator of transdiagnostic anxiety remittance and suggest that targeting AS could be useful for reducing clinical anxiety relapse following CBT.

BACKGROUND Interpretation of serial magnetic resonance imaging (MRI) for glioblastoma following radiation therapy (RT) is complicated by difficulty differentiating tumor from treatment-related changes, even using updated RANO criteria. The incorporation of novel imaging such as 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA) PET/CT to post-treatment serial imaging may improve prognostication and better facilitate future treatment decisions. METHODS The secondary analysis of a recent phase II prospective clinical trial of 18F-DOPA PET/CT-directed dose-escalated RT included patients with IDH-wildtype, MGMT-unmethylated glioblastoma who underwent post-treatment serial 18F-DOPA PET/CT surveillance. Quantitative features were extracted from pre-RT and post-RT serial PET/CT images, and robust prognostic features were selected using an in-house workflow. Both an automated machine learning (ML) algorithm and an interpretable ML algorithm were utilized to correlate surveillance PET image features with subsequent survival of greater than 12 months versus less than 12 months from the surveillance timepoint. Changes from pre-RT to post-RT PET/CT (delta model) were also assessed for association with post-RT survival and validated with a separate cohort. RESULTS Thirty-five patients with IDH-wildtype, MGMT-unmethylated glioblastoma who had at least one available (range: 1-14) post-treatment 18F-DOPA PET/CT were included. Twenty-four were used for model training, while 11 were used for validation. Ultimately, a five-feature post-RT model utilizing two shape, two texture, and one first-order radiomic feature was selected. For the delta model, five texture, two shape, and one first order radiomic feature were selected. The models show 90% accuracy in predicting survival < 12 months post-surveillance on the training set, and 68%-73% accuracy (AUC 0.64-0.73) for the validation cohort. Delta features were significantly associated with overall survival (p < 0.05). CONCLUSIONS Post-RT serial 18F-DOPA PET/CT imaging can help distinguish true tumor progression in patients with glioblastoma using a radiomics model. Tumor response evaluated for changes from pre-RT to post-RT 18F-DOPA PET/CT also predicted subsequent overall survival.

BackgroundMutations in the L/M cone opsin gene array cause abnormally high perceived retinal contrast and the development of myopia. Environmental factors may also lead to high visual contrast and cause myopia. Diffusion optics technology (DOT) lenses are designed to reduce contrast signalling in the retina and slow myopia progression.MethodsTheControl of Myopia UsingPeripheral Diffusion LensesEfficacy andSafetyStudy (CYPRESS,NCT03623074) is a 36-month, multicentre, randomised, controlled, double-masked trial evaluating two investigational spectacle lenses versus control lenses in myopic children aged 6–10, with a planned interim analysis at 12 months. The primary endpoints are change from baseline in axial length (AL) and spherical equivalent refraction (SER).Results256 children (58% female; mean age at screening, 8.1 years) were dispensed spectacles. Across all groups, baseline averages were AL 24.02 mm (SD±0.77 mm), SER −2.01 D (SD±0.9 D) using manifest refraction, and SER −1.94 D (SD±1.0 D) using cycloplegic autorefraction. At 12 months, mean difference in SER progression for test 1 versus control was −0.40 D (pConclusion12-month results from this ongoing trial demonstrate the safety and effectiveness of DOT spectacles for reducing myopic progression.

Lab-based fear-conditioning studies have repeatedly implicated exaggerated threat reactivity to benign (unreinforced) stimuli as concurrent markers of clinical anxiety, but little work has examined the strength of false alarms as a longitudinal predictor of anxiety problems. As such, we tested whether heightened false alarms of conditioned threat assessed in participants' first semester of college predicted second-semester symptoms of generalized anxiety disorder (GAD) and social anxiety disorder (SAD) - two anxiety conditions that are common in college students, have been associated with excessive false alarms, and have yet to be assessed with longitudinal conditioning designs. Here, we focused on the predictive effects of behavioral threat responses (threat expectancy, subjective anxiety, avoidance) given their greater potential for translation to the clinic. Results implicate conditioning-related increases in anxiety to safe stimuli resembling the danger-cue as prospective predictors of GAD. In contrast, SAD was predicted by non-specific elevations in anxiety to a broad set of safe stimuli, as well as by increased threat expectancy toward cues least resembling the conditioned danger cue. These findings suggest that risk for GAD and SAD are captured by distinct, behavioral indicators of false-alarms that may be more feasibly collected in clinical settings compared to alternative experimental anxiety measures like psychophysiological responses.

BACKGROUND: Patients with metastatic colorectal cancer with the BRAF V600E mutation have a poor prognosis, with a median overall survival of 4 to 6 months after failure of initial therapy. Inhibition of BRAF alone has limited activity because of pathway reactivation through epidermal growth factor receptor signaling. METHODS: In this open-label, phase 3 trial, we enrolled 665 patients with BRAF V600E-mutated metastatic colorectal cancer who had had disease progression after one or two previous regimens. Patients were randomly assigned in a 1:1:1 ratio to receive encorafenib, binimetinib, and cetuximab (triplet-therapy group); encorafenib and cetuximab (doublet-therapy group); or the investigators' choice of either cetuximab and irinotecan or cetuximab and FOLFIRI (folinic acid, fluorouracil, and irinotecan) (control group). The primary end points were overall survival and objective response rate in the triplet-therapy group as compared with the control group. A secondary end point was overall survival in the doublet-therapy group as compared with the control group. We report here the results of a prespecified interim analysis. RESULTS: The median overall survival was 9.0 months in the triplet-therapy group and 5.4 months in the control group (hazard ratio for death, 0.52; 95% confidence interval [CI], 0.39 to 0.70; P

A broad diversity of biological organisms and systems interact with soil in ways that facilitate their growth and survival. These interactions are made possible by strategies that enable organisms to accomplish functions that can be analogous to those required in geotechnical engineering systems. Examples include anchorage in soft and weak ground, penetration into hard and stiff subsurface materials and movement in loose sand. Since the biological strategies have been ‘vetted’ by the process of natural selection, and the functions they accomplish are governed by the same physical laws in both the natural and engineered environments, they represent a unique source of principles and design ideas for addressing geotechnical challenges. Prior to implementation as engineering solutions, however, the differences in spatial and temporal scales and material properties between the biological environment and engineered system must be addressed. Current bio-inspired geotechnics research is addressing topics such as soil excavation and penetration, soil–structure interface shearing, load transfer between foundation and anchorage elements and soils, and mass and thermal transport, having gained inspiration from organisms such as worms, clams, ants, termites, fish, snakes and plant roots. This work highlights the potential benefits to both geotechnical engineering through new or improved solutions and biology through understanding of mechanisms as a result of cross-disciplinary interactions and collaborations.

Intolerance of uncertainty (IU) has been conceptualized as a transdiagnostic vulnerability for emotional psychopathology, but few studies have tested whether it prospectively predicts emotional psychopathology, and none have utilized transdiagnostic and clinician-rated outcomes. To fill this gap, the present study tested whether IU prospectively predicted the clinician-rated severity of transdiagnostic emotional psychopathology six months later in a treatment-seeking Veteran sample. Participants completed the Intolerance of Uncertainty 12-item scale (IUS-12) and the Structured Clinical Interview for the DSM-5 (SCID-5) at Time 1 and again six-months later (Time 2); assessed emotional disorders included both anxiety-related disorders (i.e., post-traumatic stress disorder, generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive compulsive disorder, specific phobia) and depressive conditions (i.e., major depressive disorder and persistent depressive disorder). Linear regression analyses revealed a bidirectional prospective relation between IU and emotional psychopathology, wherein higher Time 1 IUS-12 predicted greater Time 2 emotional disorder severity and greater Time 1 emotional disorder severity predicted higher Time 2 IUS-12. Follow-up analyses revealed that IU prospectively predicted the maintenance (but not the development) of anxiety-related issues, whereas prediction of Time 2 depression was nullified when controlling for Time 1 anxiety pathology. These findings implicate IU as a transdiagnostic vulnerability for emotional psychopathology and suggest the construct can be particularly useful as a treatment target and prognostic indicator for anxiety-related conditions.

Thermo-hydro-mechanical (THM) processing can improve the intrinsic properties of wood, produce new materials, and give desired form and function to new applications. THM treatments change the mechanical properties of wood and may change its viscoelastic properties as well. Therefore, the objective of this study was to assess the viscoelastic properties of THM-treated wood at several humidity and load levels. To explore these changes, this study applied a THM treatment to beech (Fagus sylvatica L.) wood with steam (620kPa) and heat (170°C), followed by densifcation and increased temperature (200°C) in a hot-press, which was then cooled while under pressure. Two initial specimen thicknesses before THM treatment were used to study the diference between density ratios. Specimens were tested in a humidity-controlled dynamic mechanical analyser (DMA) to apply creep stress with diferent loading levels (20% and 30% of expected modulus of rupture) and relative humidity levels (30%, 50%, and 65% RH). The creep compliance/recovery response was monitored, and dynamic moduli were measured before and after the application of creep stress. The loss modulus measured was highest for specimens tested at 65% RH and lowest in specimens tested at 30% RH, which is a direct result of the viscous response of the material. Increased damping of the specimens was also observed at higher RH, which is typical for wood products due to added moisture in the cell wall acting as a plasticizer to cell wall polymers. Like previous studies, THM treatment lowered the equilibrium moisture content (EMC) of densifed wood specimens, which afected their mechanical performance. THM treatment yields higher strength and lower EMC, suggesting that this product could be suitable for structural applications where their service life is in an indoor environment. THM treatment also resulted in decreased creep compliance and recovery compliance as compared to control specimens.

Our previous work demonstrated that 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (Patients with newly diagnosed, histologically confirmed glioblastoma aged ≥18 years without contraindications toBetween January 2014 and December 2018, 75 evaluable patients were enrolled (39 DE-Un, 24 methylated [DE-Mth], and 12 indeterminate). PFS6 for DE-Un was 79.5% (95% confidence interval, 63.1%-90.1%). Median PFS was longer for DE-Un patients compared with historical controls (8.7 months vs 6.6 months; P = .017). OS was similarly longer, but the difference was not significant (16.0 vs 13.5 months; P = .13). OS was significantly improved for DE-Mth patients compared with HC-Mth (35.5 vs 23.3 months; P = .049) despite nonsignificant improvement in PFS (10.7 vs 9.0 months; P = .26). Grade 3 central nervous system necrosis occurred in 13% of patients, but treatment with bevacizumab improved symptoms in all cases.

The Muon Ionization Cooling Experiment (MICE) at the Rutherford Appleton Laboratory has collected extensive data to study the ionization cooling of muons. Several million individual particle tracks have been recorded passing through a series of focusing magnets in a number of different configurations and a liquid hydrogen or lithium hydride absorber. Measurement of the tracks upstream and downstream of the absorber has shown the expected effects of 4D emittance reduction. Further studies are providing more and deeper insight.

Treatment plans employed by physical therapists involved in musculoskeletal rehabilitation may follow a conventional medical-model approach, isolating care at the tissue level but neglecting consideration for neurocognitive contributions to recovery. Understanding and integration of motor learning concepts into physical therapy practice is integral for influencing the human movement system in the most effective manner. One such motor learning concept is the use of verbal instruction to influence the attentional focus of the learner. Evidence suggests that encouraging an external focus of attention through verbal instruction promotes superior motor performance, and more lasting effects of a learning experience than an internal focus of attention. Utilizing an external focus of attention when instructing a patient on a motor task may facilitate improved motor performance and improved functional outcomes in treatment plans devised to address musculoskeletal injury and movement disorders. The purpose of this review is to summarize the basic principles of motor learning and available evidence on the influence an external focus of attention has on motor learning and performance, including the benefits of an external focus of attention over an internal focus of attention and how therapists may inadvertently encourage the latter. Furthermore, the benefits of possessing greater awareness of neurocognitive mechanisms are discussed to exhibit how implementing such concepts into musculoskeletal rehabilitation can maximize treatment outcomes. Level of evidence 5.

Allogeneic stem-cell transplant (allo-SCT) is the standard of care for pediatric patients with acute lymphoblastic leukemia (ALL) who relapse after frontline chemotherapy; however, for patients who relapse after allo-SCT, outcomes are very poor. Few studies have examined overall survival in this patient population, particularly in patients who received a second allo-SCT.This was a retrospective analysis using data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. The study population included patients aged 3 to 21 years who were diagnosed with B-ALL and underwent their first allo-SCT between 2009 and 2013. The primary endpoint was the time from the date of posttransplant relapse to the date of death due to any reason.Outcomes in 1349 pediatric and young-adult patients were included in this analysis. The Kaplan-Meier estimated probability of survival at 3 years after first allo-SCT was 63.1% (95% CI, 60.2%-65.8%). Overall, 29.2% of patients relapsed after first allo-SCT and had a median survival of 7.4 months (95% CI, 6.0-9.6 months). Twenty-five patients in the analysis developed secondary malignancies, most of which were lymphoproliferative disorders.Survival rates are low in pediatric and young-adult patients who relapse after first and second allo-SCT, and new therapies are needed to improve outcomes in this population. This data can be used as a historical comparison for single-arm trials of novel therapies for this patient population, including chimeric antigen receptor T-cell therapy.

Chimeric antigen receptor (CAR) T-cell therapy is an investigational immunocellular therapy that reprograms a patient's cytotoxic T cells to engage and eliminate malignant cells. CAR T-cell therapies targeting the CD19 antigen have demonstrated high efficacy in clinical trials for patients with B-cell malignancies and may potentially be available on a broader scale in the future. CAR T-cell therapy begins with the collection of a sufficient number of T cells from a patient's peripheral blood through leukapheresis. Several factors must be considered when patients undergo leukapheresis for CAR T-cell therapy, including age and prior therapies. The leukapheresis material is shipped to a manufacturing facility, followed by return of the CAR T cells to the treatment center. Careful coordination of a multidisciplinary team composed of physicians, nurses, pharmacists and other hospital personnel is critical for the proper care of the patient before, during and after CAR T-cell therapy. CAR T-cell therapy has been associated with adverse events (AEs) such as cytokine release syndrome, which requires rapid attention by the emergency department, intensive care unit and hospital pharmacy. In this review, we discuss several aspects of institutional preparation for leukapheresis, CAR T-cell infusion and AE management based on our experience with clinical trials of the CD19 CAR T-cell therapy CTL019.

The selective patterning of silver nanoparticles by a patent pending process to act as a catalyst for metallization with electroless copper was explored on cotton, with a view towards application in the wearable technology sector. Whole area coverage or tracks serving as point-to-point connections were achieved by depositing the catalyst via spraying, or in more controlled manner using a microdispenser, respectively. Optimization of the catalyst deposition is described, including substrate characterization via contact angle, FTIR and surface charge measurement. The effects of the copper plating bath temperature and dwell time in the plating bath are examined. With plating times as short as 10 min, samples of good conductivity (sheet resistance, R =

Background Many patients with chronic myeloid leukemia in chronic phase experience chronic treatment-related adverse events (AEs) during imatinib therapy. These AEs can impair quality of life and lead to reduced treatment adherence, which is associated with poor clinical outcomes. Patients and Methods In the phase II ENRICH (Exploring Nilotinib to Reduce Imatinib Related Chronic Adverse Events) study (N = 52), the effect of switching patients with imatinib-related chronic low-grade nonhematologic AEs from imatinib to nilotinib was evaluated. Results Three months after switching to nilotinib, 84.6% of the patients had overall improvement in imatinib-related AEs (primary endpoint). Of 210 imatinib-related AEs identified at baseline, 62.9% had resolved within 3 months of switching to nilotinib. Of evaluable patients, most had improvements in overall quality of life after switching to nilotinib. At screening, 65.4% of evaluable patients had a major molecular response ( BCR-ABL1 ≤ 0.1% on the International Scale). After switching to nilotinib, the rate of the major molecular response was 76.1% at 3 months and 87.8% at 12 months. Treatment-emergent AEs reported with nilotinib were typically grade 1 or 2; however, some patients developed more serious AEs, and 8 patients discontinued nilotinib because of new or worsening AEs. Conclusion Overall, results from the ENRICH study demonstrated that switching to nilotinib can mitigate imatinib-related chronic low-grade nonhematologic AEs in patients with chronic myeloid leukemia in chronic phase, in conjunction with acceptable safety and achievement of molecular responses. This trial was registered at www.clinicaltrials.gov as NCT00980018.

A collaborative research programme between project partners Microsemi, the National Physical Laboratory (NPL) and Gwent Electronic Materials (GEM), has successfully developed innovative materials specifically designed to offer an alternative for high Pb or Au content materials to increase the operating temperature of electronic assemblies. Currently, for electronic assemblies to operate at high temperature, they must use a high lead solder or a very expensive gold based solder to withstand these temperatures. The ELCOSINT project has developed an inexpensive lead-free alternative for joining high temperature electronics suitable for operating at temperatures above 250°C utilising standard surface mount assembly processes. This paper summarises the work undertaken by the authors to develop and better understand this new family of electrical interconnection materials. The project brought together a materials supplier (GEM – Gwent Electronic Materials), an end-user (MSL - Microsemi) and an technology research organisation (NPL – National Physical Laboratory) to jointly develop, test and implement in production, the solution based on silver-loaded silicone materials. This paper focuses on the testing and materials evaluation undertaken at NPL to determine the long term performance of these alternative materials including high temperature ageing up to 300°C, thermal cycling and damp heat testing. Details of the shear strength and electrical performance of interconnects between the substrates and components during the test regimes are given. The manufacturing process is outlined including details of the test vehicles utilised. The processing temperature for the conductive adhesive is 250°C which offers additional advantages in potential improvements in component and substrate reliability compared to soldered solutions which would typically be processed at temperatures above 300°C.

4039 Background: In the BEACON CRC study, the triplet regimen of encorafenib (ENCO) + binimetinib (BINI) + cetuximab (CETUX) significantly improved overall survival (OS, HR:0.52, P < 0.0001) and objective response rates (ORR, 26% vs 2%, P < 0.0001) in patients (pts) with BRAFV600E metastatic colorectal cancer (mCRC) compared with current standard of care. This analysis focuses on the patient-reported quality of life (QOL) assessments from this study. Methods: The BEACON CRC study was a randomized, open-label, 3-arm, phase 3 global study which evaluated triplet (ENCO+BINI+CETUX) or doublet (ENCO+CETUX) vs. investigator’s choice of irinotecan + CETUX or FOLFIRI + CETUX in pts with BRAFV600E mCRC. QOL assessments (secondary endpoints in the trial) included the EORTC QOL Questionnaire (QLQ C30), Functional Assessment of Cancer Therapy Colon Cancer (FACT C), EuroQol 5D 5L, and Patient Global Impression of Change (PGIC). The primary assessment for the QOL variables was the time to definitive 10% deterioration. The study is ongoing. Results: 665 pts were randomly assigned to receive either triplet (n = 224), doublet (n = 220), or control (n = 221). Reduction in the risk of QOL deterioration was an estimated 45% (HR 0.55, 95% CI: 0.43, 0.70) and 52% (HR 0., 9485% CI: 0.38, 0.62) in EORTC QLQ C30 and FACT C assessments, respectively, in favor of the triplet regimen over control. For the doublet vs. control, reduction in risk of QOL deterioration was an estimated 46% (HR 0.54, 95% CI: 0.43, 0.69) and 54% (HR 0.46, 95% CI: 0.36, 0.59) in EORTC QLQ C30 and FACT C, respectively in favor of the doublet. Similar results were observed in EuroQol 5D 5L and PGIC assessments. There were no overall differences in QOL between triplet and doublet across the 4 instruments. Conclusions: In BEACON CRC, triplet and doublet demonstrated substantial improvement in patient-reported QOL assessments over the current standard of care in pts with BRAFV600E-mutant metastatic CRC whose disease had progressed after 1 or 2 prior regimens. Clinical trial information: NCT02928224 .

The patient was a 41-year-old man who injured his right shoulder falling onto his outstretched hand while skiing. Radiographs taken in the emergency department demonstrated a 3-part fracture dislocation of the proximal humerus for which he underwent same-day surgery. Physical therapy was initiated on postoperative day 27, and postoperative radiographs and physical examination results assisted in devising an appropriate plan of care and treatment. J Orthop Sports Phys Ther 2018;48(9):728. doi:10.2519/jospt.2018.6208.

TO THE EDITOR: Genetically reprogrammed T-cell therapy is a novel treatment approach being investigated in various hematologic malignancies, including relapsed and refractory pediatric B-cell acute lymphoblastic leukemia (B-ALL), multiple myeloma, diffuse large B-cell lymphoma, and chronic

The Muon Ionization Cooling Experiment (MICE) was designed to demonstrate a measurable reduction in beam emittance due to ionization cooling. The emittance of a variety of muon beams was reconstructed before and after a “cooling cell”, allowing the change in the phase-space distribution due to the presence of an absorber to be measured. The core of the MICE experiment is a cooling cell that can contain a range of solid and cryogenic absorbers inside a focussing solenoid magnet. For the data described here, a single lithium hydride (LiH) absorber was installed and two different emittance beam have been analysed. Distributions that demonstrate emittance increase and equilibrium have been reconstructed, in agreement with theoretical predictions. Data taken during 2016 and 2017 is currently being analysed to evaluate the change in emittance with a range of absorber materials, different initial emittance beams and various magnetic lattice settings. The current status and the most recent results of these analyses is presented.