PMG Research

In the volatile biotech sector, strategic alliances between startups and pharmaceutical incumbents are essential yet vulnerable. When these partnerships dissolve, they often trigger sharp negative market reactions. This paper introduces the Strategic Shock Risk Index (SSRI), a pre-event, regression-based model that quantifies the expected market impact of alliance breakdowns. Using pre-termination features, including deal size, duration, dependency, financial buffer, prior terminations, clinical phase, and contract structure (e.g., unilateral exit rights), the model employs a flexible quadratic regression with standardized nonlinear interaction terms. SSRI scores demonstrate strong predictive power (<tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$\mathrm{R}^{2}=0.82$</tex>, AUC =0.96), capturing over 80% of the variance in post-termination abnormal returns. The SSRI estimates the severity of a termination, enabling proactive risk assessment and mitigation planning. Validated on a novel alliance dataset, the model serves both as a decision-support tool and a theoretical contribution to alliance risk analysis in innovation ecosystems.

The advent of Brain-Computer Interface (BCI) technology brings groundbreaking advancements in medical science but also raises important ethical considerations. This manuscript explores the ethical dimensions of implantable BCIs (iBCIs), focusing on the central role of Institutional Review Boards (IRBs) in the United States, in safeguarding participant rights and welfare. As federally mandated bodies, IRBs ensure that informed consent is obtained ethically, emphasizing participant autonomy, preventing undue coercion, while supporting clear and practical communication of risks and benefits. As part of this discussion, this paper touches on the ethical challenges surrounding the enrollment of participants with impaired consent capacity and the long-term implications of implanted brain devices. Additionally, this work underscores the critical importance of robust cybersecurity measures to prevent data breaches and unauthorized manipulation of brain activity. By examining risk assessments, data management practices, and the need for external cybersecurity expertise, this work offers a comprehensive framework for IRB review of iBCI research. This perspective aims to guide ethical iBCI research and protect human subjects in this rapidly evolving field.

ABSTRACTBackgroundREGEN-COV antibody cocktail (casirivimab with imdevimab) rapidly reduced viral load and decreased medically-attended visits in the phase 1/2 portion of this trial; REGEN-COV, retains activity in vitro against emerging SARS-CoV-2 variants of concern.MethodsThe phase 3 portion of this adaptive, randomized, master protocol, included 4,057 Covid-19 outpatients with one or more risk factors for severe disease. Patients were randomized to a single treatment of intravenous placebo, or various doses of REGEN-COV, and followed for 28 days. The prespecified hierarchical analysis first compared REGEN-COV 2400mg dose vs concurrent placebo, then compared the 1200mg dose vs concurrent placebo, for endpoints assessing risk of hospitalization or death, and time to symptom resolution. Safety was evaluated in all treated patients.ResultsBoth REGEN-COV 2400mg and 1200mg significantly reduced Covid-19-related hospitalization or all-cause death compared to placebo (71.3% reduction [1.3% vs 4.6%; p&lt;0.0001] and 70.4% reduction [1.0% vs 3.2%; p=0.0024], respectively). The median time to resolution of Covid-19 symptoms was 4 days shorter in both dose arms vs placebo (10 vs 14 days; p&lt;0.0001). Efficacy of REGEN-COV was consistent across subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. REGEN-COV more rapidly reduced viral load than placebo. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200mg (1.1%) and 2400mg (1.3%) groups and grade ≥2 infusion-related reactions were infrequent (&lt;0.3% in all groups).ConclusionsTreatment with REGEN-COV was well-tolerated and significantly reduced Covid-19-related hospitalization or all-cause death, rapidly resolved symptoms, and reduced viral load.(Funded by Regeneron Pharmaceuticals and the Biomedical and Advanced Research and Development Authority of the Department of Health and Human Services; ClinicalTrials.gov number, NCT04425629.)

Background: Suboptimal radiofrequency ablation (RF) lesions may result from either poor catheter tip-tissue contact, or inadequate energy deposition resulting in discontinuous or non-transmural lesions. A system and method were assessed for using real-time optical tissue interrogation within the NADH fluorescence range to evaluate contact between the RF catheter tip and myocardium, monitor the progression of ablation lesions, linear lesions and evaluation of new multi-directional monitoring from the catheter tip in real time during RF delivery. Methods And Results: An irrigated RF ablation catheter incorporating imaging optics (LuxCath, LLC) was inserted transvenously into the heart chambers of 9 anesthetized swine. Light (360 + /-25nm) was delivered into the cardiac tissue. The fluoresced response from 370 nm to 660 nm was captured via spectrometer and analyzed in real time. Spectral data was acquired pre, during, and post formation of the RF lesions. Two types of plots were created for each lesion: intensity (in counts) vs. wavelength (nm), and 465nm peak amplitude (normalized) vs. time (sec). Myocardium fNADH response over time during ablation is an indication of tip to tissue contact. fNADH correlates with the physiology of the ablation lesions, healthy tissue having the highest fluorescence intensity and ablated tissue having the lowest fNADH. A smooth response plot during lesion creation indicates stable tip to tissue contact. A sharper response is an indication of intermittent or shifting tip to tissue contact. Overlay of the spectral plots of tissue fluorescence during ablations demonstrate a stable diminishing signature in the plotted spectra as an indication of catheter stability and successful lesion creation. Shifting signatures indicate tip movement during an ablation. When the tip shifts from predominantly myocardium to an area with more collagen or elastin the spectral plot has a characteristic change that helps to characterize the type of tissue at the catheter tip. Myocardial fNADH response declined by 70% +/- 10 % during 30 sec of RF ablation, with a 60% reduction occurring within the first 15 sec with the use of multi-view catheter on the last three experiments. Necropsy confirmed that the information regarding catheter contact and stability obtained by these optical means was a good predictor of lesion quality. Signatures indicating stable contact with reduction in fNADH resulted in high quality lesions. Signatures indicating unstable catheter contact resulted in poor or no lesion formation. Linear lesions were easily monitored during RF ablation. Conclusions: Real-time optical tissue characterization provides excellent assessment of electrode-tissue contact and lesion progression during RF delivery. New catheter modifications allow for distal and lateral monitoring of fNADH. Linear lesion formation was easily monitored. The catheter also provides highly valuable information regarding the myocardium and collagen tissue composition at the site of catheter tip.

<b>Introduction:</b> Dyspnea in children is a common problem. An objective measurement to evaluate the degree of dyspnea and to determine the effect of therapy in young children has not been found. Respiratory surface EMG may be a way to determine objectively the degree of dyspnea and the effect of therapy. Earlier research showed that measuring the degree of airway obstruction during histamine challenge tests in children with asthma is possible by EMG.¹ <b>Aims and objectives:</b> to determine 1<b>.</b> the difference in surface EMG activity of the diaphragm(di) in healthy children compared to dyspnoeic children; 2. the change in surface EMG activity (di) in dyspnoeic children after treatment with Salbutamol. <b>Methods:</b> one single EMG(di) measurement in 28 healthy children (mean age 35±23 months) was compared to changes in EMG(di) activity in 27 dyspnoeic children (mean age 31±21 months) before and after treatment with Salbutamol. The logarithm of the EMG-Activity-Ratio(logEMGAR) was used as EMG parameter. <b>Results:</b> The logEMGAR(di) in healthy children (mean -0,01±0,58) was significantly lower compared to dyspnoeic children (mean 0,12±0,50) of the same age (p&lt;0,05). The logEMGAR(di) in dyspnoeic children (mean 0,12±0,50) decreased significantly (p&lt;0,01) after treatment with Salbutamol (mean 0,02±0,32). <b>Conclusion:</b> This study shows a significant difference in EMG activity (di) between healthy and dyspnoeic children. Measuring the EMG activity (di) is an alternative way to determine the effect of therapy with Salbutamol in young children. 1. Maarsingh E.J. et al. Respir Med 2004; 98(4):363-72.