Precursors prior to Type IIn supernova explosions are common: precursor rates, properties, and correlations

There is a growing number of supernovae (SNe), mainly of Type IIn, which present an outburst prior to their presumably final explosion. These precursors may affect the SN display, and are likely related to some poorly charted phenomena in the final stages of stellar evolution. Here we present a sample of 16 SNe IIn for which we have Palomar Transient Factory (PTF) observations obtained prior to the SN explosion. By coadding these images taken prior to the explosion in time bins, we search for precursor events. We find five Type IIn SNe that likely have at least one possible precursor event, three of which are reported here for the first time. For each SN we calculate the control time. Based on this analysis we find that precursor events among SNe IIn are common: at the one-sided 99% confidence level, more than 50% of SNe IIn have at least one pre-explosion outburst that is brighter than absolute magnitude -14, taking place up to 1/3 yr prior to the SN explosion. The average rate of such precursor events during the year prior to the SN explosion is likely larger than one per year, and fainter precursors are possibly even more common. We also find possible correlations between the integrated luminosity of the precursor, and the SN total radiated energy, peak luminosity, and rise time. These correlations are expected if the precursors are mass-ejection events, and the early-time light curve of these SNe is powered by interaction of the SN shock and ejecta with optically thick circumstellar material.Comment: 15 pages, 20 figures, submitted to Ap

Tumor Tissue Explant Culture of Patient-Derived Xenograft as Potential Prioritization Tool for Targeted Therapy

Despite of remarkable progress made in the head and neck cancer (HNC) therapy, the survival rate of this metastatic disease remain low. Tailoring the appropriate therapy to patients is a major challenge and highlights the unmet need to have a good preclinical model that will predict clinical response. Hence, we developed an accurate and time efficient drug screening method of tumor ex vivo analysis (TEVA) system, which can predict patient-specific drug responses. In this study, we generated six patient derived xenografts (PDXs) which were utilized for TEVA. Briefly, PDXs were cut into 2 × 2 × 2 mm3 explants and treated with clinically relevant drugs for 24 h. Tumor cell proliferation and death were evaluated by immunohistochemistry and TEVA score was calculated. Ex vivo and in vivo drug efficacy studies were performed on four PDXs and three drugs side-by-side to explore correlation between TEVA and PDX treatment in vivo. Efficacy of drug combinations was also ventured. Optimization of the culture timings dictated 24 h to be the time frame to detect drug responses and drug penetrates 2 × 2 × 2 mm3 explants as signaling pathways were significantly altered. Tumor responses to drugs in TEVA, significantly corresponds with the drug efficacy in mice. Overall, this low cost, robust, relatively simple and efficient 3D tissue-based method, employing material from one PDX, can bypass the necessity of drug validation in immune-incompetent PDX-bearing mice. Our data provides a potential rationale for utilizing TEVA to predict tumor response to targeted and chemo therapies when multiple targets are proposed

Functional integrity of the shoulder joint and pectoralis major following subpectoral implant breast reconstruction

Subpectoral implants for breast reconstruction after mastectomy requires the surgical disinsertion of the sternocostal fiber region of the pectoralis major. This technique is associated with significant shoulder strength and range of motion deficits, but it is unknown how it affects the underlying integrity of the shoulder joint or pectoralis major. The aim of this study was to characterize the long‐term effects of this reconstruction approach on shoulder joint stiffness and pectoralis major material properties. Robot‐assisted measures of shoulder strength and stiffness and ultrasound shear wave elastography images from the pectoralis major were acquired from 14 women an average of 549 days (range: 313–795 days) post reconstruction and 14 healthy, age‐matched controls. Subpectoral implant patients were significantly weaker in shoulder adduction (p < 0.001) and exhibited lower shoulder stiffness when producing submaximal adduction torques (p = 0.004). The underlying material properties of the clavicular fiber region of the pectoralis major were altered in subpectoral implant patients, with significantly reduced shear wave velocities in the clavicular fiber region of the pectoralis major when generating adduction torques (p = 0.023). The clinical significance of these findings are that subpectoral implant patients do not fully recover shoulder strength or stability in the long‐term, despite significant recovery time, and substantial shoulder musculature left intact. The impact of these procedures extends to the remaining, intact volume of the pectoralis major. Optimization of shoulder function should be a key aspect of the post‐reconstruction standard of care. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1610–1619, 2019.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149750/1/jor24257.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149750/2/jor24257_am.pd

Individually based measurement of temporal summation evoked by a noxious tonic heat paradigm

Background: A model for measuring temporal summation (TS) by tonic noxious stimulation was recently proposed. However, methodological variations between studies make it difficult to reach a consensus regarding the way TS should be applied and calculated. The present study aimed to present a calculation method of TS magnitude produced by a tonic heat model in a large cohort of healthy subjects. Methods: Noxious heat stimulation (46.5°C/2 minutes) was applied to the forearm of 154 subjects who continuously rated pain intensity using a computerized visual analog scale. TS was calculated by “mean group” and “individual” approaches. Results: A “typical” pattern of pain response, characterized by a peak pain followed by a decrease in intensity to a nadir and subsequently a progressive increase in pain scores, was exhibited by 86.4% of the subjects. Using the “mean group” and “individual” calculation approaches, the mean ± standard deviation magnitudes of TS were 31.4±27.5 and 41.0±26.0, respectively (P<0.001). Additionally, using the individualized approach, we identified a different (“atypical”) response pattern among the rest of the subjects (13.6%). Conclusion: The results support the tonic heat model of TS for future utilization. The individualized TS calculation method seems advantageous since it better reflects individual magnitudes of TS

Migraine Frequency Decrease Following Prolonged Medical Cannabis Treatment: A Cross-Sectional Study

Background: Medical cannabis (MC) treatment for migraine is practically emerging, although sufficient clinical data are not available for this indication. This cross-sectional questionnaire-based study aimed to investigate the associations between phytocannabinoid treatment and migraine frequency. Methods: Participants were migraine patients licensed for MC treatment. Data included self-reported questionnaires and MC treatment features. Patients were retrospectively classified as responders vs. non-responders (&ge;50% vs. &lt;50% decrease in monthly migraine attacks frequency following MC treatment initiation, respectively). Comparative statistics evaluated differences between these two subgroups. Results: A total of 145 patients (97 females, 67%) with a median MC treatment duration of three years were analyzed. Compared to non-responders, responders (n = 89, 61%) reported lower current migraine disability and lower negative impact, and lower rates of opioid and triptan consumption. Subgroup analysis demonstrated that responders consumed higher doses of the phytocannabinoid ms_373_15c and lower doses of the phytocannabinoid ms_331_18d (3.40 95% CI (1.10 to 12.00); p &lt; 0.01 and 0.22 95% CI (0.05&ndash;0.72); p &lt; 0.05, respectively). Conclusions: These findings indicate that MC results in long-term reduction of migraine frequency in &gt;60% of treated patients and is associated with less disability and lower antimigraine medication intake. They also point to the MC composition, which may be potentially efficacious in migraine patients

Functional integrity of the shoulder joint and pectoralis major following subpectoral implant breast reconstruction

Subpectoral implants for breast reconstruction after mastectomy requires the surgical disinsertion of the sternocostal fiber region of the pectoralis major. This technique is associated with significant shoulder strength and range of motion deficits, but it is unknown how it affects the underlying integrity of the shoulder joint or pectoralis major. The aim of this study was to characterize the long‐term effects of this reconstruction approach on shoulder joint stiffness and pectoralis major material properties. Robot‐assisted measures of shoulder strength and stiffness and ultrasound shear wave elastography images from the pectoralis major were acquired from 14 women an average of 549 days (range: 313–795 days) post reconstruction and 14 healthy, age‐matched controls. Subpectoral implant patients were significantly weaker in shoulder adduction (p < 0.001) and exhibited lower shoulder stiffness when producing submaximal adduction torques (p = 0.004). The underlying material properties of the clavicular fiber region of the pectoralis major were altered in subpectoral implant patients, with significantly reduced shear wave velocities in the clavicular fiber region of the pectoralis major when generating adduction torques (p = 0.023). The clinical significance of these findings are that subpectoral implant patients do not fully recover shoulder strength or stability in the long‐term, despite significant recovery time, and substantial shoulder musculature left intact. The impact of these procedures extends to the remaining, intact volume of the pectoralis major. Optimization of shoulder function should be a key aspect of the post‐reconstruction standard of care. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1610–1619, 2019.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149750/1/jor24257.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149750/2/jor24257_am.pd

CDK 4/6 Inhibition Overcomes Acquired and Inherent Resistance to PI3Kα Inhibition in Pre-Clinical Models of Head and Neck Squamous Cell Carcinoma

Activating alterations in PIK3CA, the gene coding for the catalytic subunit of phosphoinositide-3-kinase (PI3K), are prevalent in head and neck squamous cell carcinoma (HNSCC) and thought to be one of the main drivers of these tumors. However, early clinical trials on PI3K inhibitors (PI3Ki) have been disappointing due to the limited durability of the activity of these drugs. To investigate the resistance mechanisms to PI3Ki and attempt to overcome them, we conducted a molecular-based study using both HNSCC cell lines and patient-derived xenografts (PDXs). We sought to simulate and dissect the molecular pathways that come into play in PIK3CA-altered HNSCC treated with isoform-specific PI3Ki (BYL719, GDC0032). In vitro assays of cell viability and protein expression indicate that activation of the mTOR and cyclin D1 pathways is associated with resistance to PI3Ki. Specifically, in BYL719-resistant cells, BYL719 treatment did not induce pS6 and pRB inhibition as detected in BYL719-sensitive cells. By combining PI3Ki with either mammalian target of rapamycin complex 1 (mTORC1) or cyclin D1 kinase (CDK) 4/6 specific inhibitors (RAD001 and abemaciclib, respectively), we were able to overcome the acquired resistance. Furthermore, we found that PI3Ki and CDK 4/6 inhibitors have a synergistic anti-tumor effect when combined in human papillomavirus (HPV)-negative/PIK3CA-WT tumors. These findings provide a rationale for combining PI3Ki and CDK 4/6 inhibitors to enhance anti-tumor efficacy in HNSCC patients

The effectiveness and safety of medical cannabis for treating cancer related symptoms in oncology patients.

The use of medical cannabis (MC) to treat cancer-related symptoms is rising. However, there is a lack of long-term trials to assess the benefits and safety of MC treatment in this population. In this work, we followed up prospectively and longitudinally on the effectiveness and safety of MC treatment. Oncology patients reported on multiple symptoms before and after MC treatment initiation at one-, three-, and 6-month follow-ups. Oncologists reported on the patients' disease characteristics. Intention-to-treat models were used to assess changes in outcomes from baseline. MC treatment was initiated by 324 patients and 212, 158 and 126 reported at follow-ups. Most outcome measures improved significantly during MC treatment for most patients (p < 0.005). Specifically, at 6 months, total cancer symptoms burden declined from baseline by a median of 18%, from 122 (82–157) at baseline to 89 (45–138) at endpoint (−18.98; 95%CI= −26.95 to −11.00; p < 0.001). Reported adverse effects were common but mostly non-serious and remained stable during MC treatment. The results of this study suggest that MC treatment is generally safe for oncology patients and can potentially reduce the burden of associated symptoms with no serious MC-related adverse effects

Short-Term Medical Cannabis Treatment Regimens Produced Beneficial Effects among Palliative Cancer Patients

In the last decade the use of medical cannabis (MC) for palliative cancer treatment has risen. However, the choice between products is arbitrary and most patients are using Tetrahydrocannabinol (THC)-dominant cannabis products. In this study, we aimed to assess the short-term outcomes of MC treatment prescribed by oncologists in relation to the type of cannabis they receive. A comparative analysis was used to assess the differences in treatment effectiveness and safety between THC-dominant (n = 56, 52%), cannabidiol (CBD)-dominant (n = 19, 18%), and mixed (n = 33, 30%) MC treatments. Oncology patients (n = 108) reported on multiple symptoms in baseline questionnaires, initiated MC treatment, and completed a one-month follow-up. Most parameters improved significantly from baseline, including pain intensity, affective and sensory pain, sleep quality and duration, cancer distress, and both physical and psychological symptom burden. There was no significant difference between the three MC treatments in the MC-related safety profile. Generally, there were no differences between the three MC treatments in pain intensity and in most secondary outcomes. Unexpectedly, CBD-dominant oil treatments were similar to THC-dominant treatments in their beneficial effects for most secondary outcomes. THC-dominant treatments showed significant superiority in their beneficial effect only in sleep duration compared to CBD-dominant treatments. This work provides evidence that, though patients usually consume THC-dominant products, caregivers should also consider CBD-dominant products as a useful treatment for cancer-related symptoms