Return to play following craniotomy for non-traumatic brain lesions.

Objective: Return to play (RTP) decisions after cranial surgery are important to patients. Most published data relate to RTP following sports-related brain injury. This study investigated factors that influence neurosurgical RTP decision-making following craniotomy for non-traumatic brain lesions. Methods: A patient scenario-based survey was distributed to U.S. and Europe-based neurosurgeons via the American Association of Neurological Surgeons/Congress of Neurological Surgeons Tumor Section and the European Association of Neuro-Oncology. From one core patient scenario, 5 further scenarios were developed involving patients of varying age, sport preference, tumor pathology, and craniotomy approach. Respondents provided RTP recommendations and factors important in forming these recommendations. Results: Forty-one responses were received; Europe (48%), U.S. (37%). The most commonly cited factors influencing RTP decision-making across scenarios were symptomatic recovery (85.4%), resolution of blood and/or air on imaging (43.4%), and patient demand (31.7%). The sports with the longest average RTP timeline were boxing (10.3 months), rugby (8.7 months), and American football (8.5 months) in the core patient scenario. Twenty-nine percent of neurosurgeons requested neuroimaging before determining RTP recommendations in this scenario, more commonly in America than Europe (46.7% and 5.0% respectively, p = .006). Conclusions: Although limited by sample size, the data provides a foundation to support development of a systematic approach to RTP decision-making following craniotomy for brain lesions of non-traumatic etiology. Future work to develop consensus guidelines will benefit from objective data about outcomes, particularly in relation to repeat imaging prior to RTP.

Association of Body Mass Index, Blood Pressure with Fasting Serum Glucose in Female with Type-2 Diabetes Mellitus.

Type-2 diabetes mellitus is a global pandemic with immense social, health and financial consequences. The pathophysiology of type-2 diabetes is significantly influenced by overweight and obesity. Type-2 diabetes often goes hand-in-hand with high blood pressure. One way to check type-2 diabetes is by measuring fasting blood glucose. This cross-sectional analytical study looked at how blood pressure, body mass index (BMI) and fasting serum glucose relate to each other in women with type-2 diabetes in the Mymensingh locality. The research took place at the Physiology Department of Mymensingh Medical College, Bangladesh from Octy 2023 to June 2024. We included 200 participants: 100 apparently healthy women of 30-65 years without diabetes as the control group and 100 women with diabetes of same age group as the study group. The data was analyzed using SPSS software. Weight and height were measured anthropometrically in kilograms and meters, respectively. Blood pressure was checked with an aneroid sphygmomanometer for both systolic and diastolic values. To see if there were significant differences between groups, we used the unpaired Students 't' test and shared results as mean±SD. For relationships among fasting serum glucose, blood pressure and BMI, we used Pearson's correlation coefficient test. The average BMI for those in the control group was 24.19±1.22 kg/m². In contrast, the study group's average BMI was higher at 28.04±1.66 kg/m². The study group also had a greater average systolic blood pressure of 130.65±6.06 mm Hg compared to 115.30±5.07 mm Hg for controls. For diastolic blood pressure, values were also higher in the study group: 85.65±5.71 mm Hg compared to the control's 75.65±5.25 mm Hg. Fasting serum glucose levels showed a positive correlation with both BMI and blood pressure. We recommended from this study that routine evaluation of these parameters is important for preventing complications associated with type-2 diabetes mellitus.

Montelukast deprescribing in outpatient specialty clinics: A single center cross-sectional study.

Objective: To identify and evaluate montelukast deprescribing in outpatient specialty clinics. Methods: This was a single-center, retrospective, cross-sectional study conducted at an academic health system in the southern US including 21 specialty clinics. Subjects included adults ≥18 years with an active prescription for montelukast who attended at least one appointment in pulmonology, otolaryngology, or neurology outpatient specialty clinics between January 1, 2021 to December 31, 2022. Patients <18 years and those with diagnoses of uncontrolled asthma or allergic rhinitis were excluded. Outcomes assessed included the frequency and period prevalence of montelukast deprescribing, defined by a documented montelukast discontinuation within the medical record, and evaluation of reasoning for discontinuation mentioned in visit notes. Results: There were 1152 patients who met inclusion criteria. Of these, 43 (3.7 %) experienced a montelukast deprescribing event: 18 (41.9 %) in neurology, 13 (30.2 %) in otolaryngology, and 12 (27.9 %) in pulmonology. Documented reasons for deprescribing were only available for 11 patients (25.6 %); reasons for deprescribing included patient-provider shared decision-making regarding the Black Box Warning [n = 5 (11.6 %)], inadequate treatment response [n = 3 (7.0 %)], suicidal thought development [n = 1 (2.3 %)], adverse drug event [n = 1 (2.3 %)], and pregnancy planning [n = 1 (2.3 %)]. Conclusion: Montelukast deprescribing rates were less than 5 % in outpatient specialty clinics. Factors associated with montelukast deprescribing beget further investigation.

Where You Protonate Matters: Deciphering the Unimolecular Chemistry of Protonated Myrcene and Linalool.

The unimolecular reactions of protonated myrcene and linalool were investigated by collision-induced dissociation and density functional theory calculations. Experiments on a triple quadrupole mass spectrometer showed that protonated myrcene undergoes two major unimolecular reactions losing propene and isobutene, and two minor reactions of ethene and propane loss. In each case, the product ion consists of a substituted five-member ring. Protonation of myrcene was found to form four distinct protomers, three of which can be significantly populated in the ion source. The observed fragmentation reactions were calculated and found to depend on the starting protomer. Each pathway consisted of several hydrogen-migration and ring-forming/opening steps on the way to the observed products. Likewise, protonation of linalool also produces three distinct protomers, with the global minimum being formed by protonation of a central double bond. The major reaction is water loss to form protonated myrcene, but two minor channels were also observed resulting in loss of acetone and isobutene. The calculated minimum energy reaction pathways were found to be consistent with the relative abundances of the ions in the experimental breakdown diagrams.

The utility of disc space and vertebral body specimens cell count differential for the diagnosis of native vertebral osteomyelitis: a prospective cohort study.

BACKGROUND: Diagnostic methods for native vertebral osteomyelitis (NVO) often yield inconclusive results. Image-guided spine biopsies for culture are specific but diagnose NVO in only 50% of cases. Pre-exposure to antimicrobials further reduces diagnostic yield. Our study assesses the value of neutrophil percentage in disc space fluid and vertebral body (DS/VB) samples for diagnosing NVO. METHODS: Adults referred for spine biopsy at Mayo Clinic from August 2022 to September 2023 were consented and enrolled at the time of biopsy. Following routine specimen collection, the biopsy needle was rinsed in saline into an EDTA tube for cell analysis. NVO diagnosis required organism identification in spine tissue or blood and/or positive histopathology, and consistent symptoms and imaging. RESULTS: Sixty-eight patients were prospectively enrolled, comprising 14 with NVO and 54 with alternative diagnoses. The median biopsy sample polymorphonuclear (PMN) percentage for NVO patients was 80.5% (IQR 72.5-85.2), compared to 64.5% (IQR 54.0-69.0) for those without NVO (p < 0.001). Nine (64.3%) NVO patients received antibiotics within 10 days prior to spine biopsy. As a continuous measure, PMN differential showed a moderately strong ability in classifying NVO status with an area under ROC curve of 0.795; an optimal point on the curve of 71.5% corresponded to a sensitivity of 78.6%, specificity of 79.6%, negative predictive value of 93.5% and positive predictive value of 50.0%. CONCLUSION: PMN differential in DS/VB biopsies may serve as an effective diagnostic tool in the evaluation of patients with NVO particularly in ambiguous cases with an initially negative spine biopsy. Future efforts will aim to implement these findings within routine clinical practice.

Past Trends and Future Directions of Cardiac Regenerative Medicine - A Systematic Analysis of Clinical Trial Registries.

Cell therapy, gene therapy, and tissue engineering have been explored as potential strategies to repair or regenerate damaged cardiac tissue. Despite the presence of encouraging preclinical data, clinical trials of regenerative cardiac therapies have yielded mixed results. Our study aimed to investigate the fate of all registered clinical trials within regenerative cardiac medicine, with the purpose of exploring the potential role of publication bias (or trial-completion bias), how published and unpublished research affects the field, and to draw lessons and recommendations for future clinical trials. In this analysis, we show that only a third of all registered trials has yielded results and that a significant number of trials are not completed. Furthermore, we identified significant heterogeneity in study design, study phase, funding, specific therapies used, primary outcome measures and methods of outcome assessment. These observations might hinder the successful translation of cardiac regenerative therapies into clinical practice.

Risk factors and outcomes of conversions in robotic and laparoscopic liver resections: A nationwide analysis.

BACKGROUND: Unfavorable intraoperative findings or incidents during minimally invasive liver surgery may necessitate conversion to open surgery. This study aimed to identify predictors for conversion in minimally invasive liver surgery and gain insight into outcomes following conversions. METHODS: This nationwide, retrospective cohort study compared converted and non-converted minimally invasive liver surgery procedures using data from 20 centers in the Dutch Hepatobiliary Audit (2014-2022). Propensity score matching was applied. Subgroup analyses of converted robotic liver resection versus laparoscopic liver resection and emergency versus non-emergency conversions were performed. Predictors for conversions were identified using backward stepwise multivariable logistic regression. RESULTS: Of 3,530 patients undergoing minimally invasive liver surgery (792 robotic liver resection, 2,738 laparoscopic liver resection), 408 (11.6%) were converted (4.9% robotic liver resection, 13.5% laparoscopic liver resection). Conversion was associated with increased blood loss (580 mL [interquartile range 250-1,200] vs 200 mL [interquartile range 50-500], P < .001), major blood loss (≥500 mL, 58.8% vs 26.7%, P < .001), intensive care admission (19.0% vs 8.4%, P = .005), overall morbidity (38.9% vs 21.0%, P < .001), severe morbidity (17.9% vs 9.6%, P = .002), and a longer hospital stay (6 days [interquartile range 5-8] vs 4 days [interquartile range 2-5], P < .001) but not mortality (2.2% vs 1.2%, P = .387). Emergency conversions had increased intraoperative blood loss (1,500 mL [interquartile range 700-2,800] vs 525 mL [interquartile range 208-1,000], P < .001), major blood loss (87.5% vs 59.3%, P = .005), and intensive care admission (27.9% vs 10.6%, P = .029), compared with non-emergency conversions. Robotic liver resection was linked to lower conversion risk, whereas American Society of Anesthesiologists grade ≥3, larger lesion size, concurrent ablation, technically major, and anatomically major resections were risk factors. CONCLUSION: Both emergency and non-emergency conversions negatively impact perioperative outcomes in minimally invasive liver surgery. Robotic liver resection reduces conversion risk compared to laparoscopic liver resection.

Choice architecture promotes sustainable choices in online food-delivery apps.

Greenhouse gas emissions from the food system constitute about one-third of the global total, hence mitigation in this sphere of human activity is a vital goal for research and policy. This study empirically tests the effectiveness of different interventions to reduce the carbon footprint of food choices made on food-delivery apps, using an incentive-compatible online randomized controlled trial with 4,008 participants. The experiment utilized an interactive web platform that mimics popular online food-delivery platforms (such as Just Eat) and included three treatment conditions: a sign-posted meat tax, a carbon-footprint label, and a choice-architecture intervention that changed the order of the menu so that the lowest carbon-impact restaurants and dishes were presented first. Results show that only the choice-architecture nudge significantly reduced the average meal carbon footprint-by 0.3 kg/CO2e per order (12%), driven by a 5.6 percentage point (13%) reduction in high-carbon meal choices. Moreover, we find evidence of significant health and well-being co-benefits. Menu repositioning resulted in the average meal order having greater nutritional value and fewer calories, whilst significantly increasing self-reported satisfaction with the meal choice. Simple back-of-the-envelope calculations suggest that menu repositioning would be a highly cost-effective policy instrument if implemented at scale, with the return on investment expected to be in the range of £1.28 to £3.85 per metric ton of avoided CO2 emissions, depending on implementation costs.

Effect of Elevated Body Mass Index on Outcomes of Transcatheter Aortic Valve Replacement for Severe Aortic Stenosis.

BACKGROUND: The association of body mass index (BMI) and an "obesity paradox" with cardiovascular risk prediction is controversial. This study aimed to evaluate the impact of elevated BMI on the outcome of transcatheter aortic valve replacement (TAVR) for aortic stenosis. METHODS: This retrospective study included 1019 patients with a BMI of ≥18.5 kg/m2 divided into 3 groups: 1) normal BMI (18.5-24.9 kg/m2), 2) overweight (25-29.9 kg/m2), and 3) obese (≥30 kg/m2). Propensity score matching was used to compare normal BMI with overweight and normal BMI with obese. RESULTS: The median age of the cohort was 82 years, and 348 patients had a normal BMI, while 319 and 352 patients were overweight and obese, respectively. After 1 : 1 propensity score matching, 258 and 192 pairs between normal BMI and overweight, and normal BMI and obese patients, respectively, were analyzed. Both overweight and obese patients had higher post-transaortic mean gradients and lower indexed effective orifice areas compared to normal BMI patients. During a median follow-up of 25 (range: 0.1-72) months, all-cause mortality was similar between overweight or obese patients and patients with a normal BMI. However, in a subgroup analysis of patients with moderate/severe chronic lung disease, all-cause mortality was significantly higher in obese patients compared with normal BMI patients (hazard ratio = 3.49, 95% confidence interval, 1.21-10.0, P = .021). CONCLUSIONS: In this study, the "obesity paradox" was not observed in patients undergoing TAVR; rather, in patients with significant lung disease, obesity may be associated with worse midterm outcomes after TAVR.

Exploring the role of diffusive coupling in spatiotemporal chaos.

We explore the chaotic dynamics of a large one-dimensional lattice of coupled maps with diffusive coupling of varying strength using the covariant Lyapunov vectors (CLVs). Using a lattice of diffusively coupled quadratic maps, we quantify the growth of spatial structures in the chaotic dynamics as the strength of diffusion is increased. When the diffusion strength is increased from zero, we find that the leading Lyapunov exponent decreases rapidly from a positive value to zero to yield a small window of periodic dynamics which is then followed by chaotic dynamics. For values of the diffusion strength beyond the window of periodic dynamics, the leading Lyapunov exponent does not vary significantly with the strength of diffusion with the exception of a small variation for the largest diffusion strengths we explore. The Lyapunov spectrum and fractal dimension are described analytically as a function of the diffusion strength using the eigenvalues of the coupling operator. The spatial features of the CLVs are quantified and compared with the eigenvectors of the coupling operator. The chaotic dynamics are composed entirely of physical modes for all of the conditions we explore. The leading CLV is highly localized and localization decreases with increasing strength of the spatial coupling. The violation of the dominance of Oseledets splitting indicates that the entanglement of pairs of CLVs becomes more significant between neighboring CLVs as the strength of diffusion is increased.

The Protective Role of Transcription Factor Nrf2 in Murine Macrophage Activation Syndrome.

OBJECTIVE: Macrophage activation syndrome (MAS) is characterized by multi-lineage cytopenias, hypercytokinemia, and tissue hemophagocytosis. Transcription factor Nrf2 is a master regulator of redox homeostasis. In this work we aim to investigate the role of Nrf2 in murine hyperinflammation and the mechanisms by which Nrf2 activation by red blood cell products regulates pro-inflammatory cytokine production. METHODS: We induce murine MAS in wildtype and Nrf2 knockout (Nrf2 -/-) mice by repeat administration of TLR9-agonist CpG. Clinical and biochemical markers of disease were measured including complete blood counts, liver and spleen pathology, serum free heme, ferritin, and cytokine profiles. In vitro bone marrow derived macrophages and dendritic cells were used to investigate regulation of CpG-induced cytokine expression by oxidized red blood cells and hemin. RESULTS: Patients with hyperinflammatory disease have higher levels of Nrf2 gene expression. Mice with CpG-induced hyperinflammation have elevated systemic lipid peroxidation which is exacerbated in Nrf2 -/- mice. Compared to wildtype controls, Nrf2 -/- mice develop significantly worse organomegaly, organ pathology, and reticulocytosis. Nrf2 -/- mice have exacerbated hypercytokinemia in cytokines central MAS physiology: IL-12, IFNg, and IL-10. In vitro we found that oxidized red blood cell lysates and hemin are able to suppress IL-12 transcription and protein production from bone marrow derived dendritic cells in a Nrf2-dependent manner. CONCLUSION: Together our findings show that transcription factor Nrf2 is highly expressed in patients with hyperinflammatory disease and demonstrate a protective role for Nrf2 in a murine model of MAS in part due to Nrf2-mediated suppression of proinflammatory cytokine production.

Mixed contaminant exposure in tapwater and the potential implications for human-health in disadvantaged communities in California.

Water is an increasingly precious resource in California as years of drought, climate change, pollution, as well as an expanding population have all stressed the state's drinking water supplies. Currently, there are increasing concerns about whether regulated and unregulated contaminants in drinking water are linked to a variety of human-health outcomes particularly in socially disadvantaged communities with a history of health risks. To begin to address this data gap by broadly assessing contaminant mixture exposures, the current study was designed to collect tapwater samples from communities in Gold Country, the San Francisco Bay Area, two regions of the Central Valley (Merced/Fresno and Kern counties), and southeast Los Angeles for 251 organic chemicals and 32 inorganic constituents. Sampling prioritized low-income areas with suspected water quality challenges and elevated breast cancer rates. Results indicated that mixtures of regulated and unregulated contaminants were observed frequently in tapwater throughout the areas studied and the types and concentrations of detected contaminants varied by region, drinking-water source, and size of the public water system. Multiple exceedances of enforceable maximum contaminant level(s) (MCL), non-enforceable MCL goal(s) (MCLG), and other health advisories combined with frequent exceedances of benchmark-based hazard indices were also observed in samples collected in all five of the study regions. Given the current focus on improving water quality in socially disadvantaged communities, our study highlights the importance of assessing mixed-contaminant exposures in drinking water at the point of consumption to adequately address human-health concerns (e.g., breast cancer risk). Data from this pilot study provide a foundation for future studies across a greater number of communities in California to assess potential linkages between breast cancer rates and tapwater contaminants.

The Incidence of Shoulder and Elbow Injuries in High School and Collegiate Softball Athletes: A Systematic Review.

CONTEXT: Despite increased youth and adolescent participation in fast-pitch softball and the reporting of upper extremity injuries, there remains a relative paucity of research examining shoulder and elbow injuries in high school and collegiate softball athletes. OBJECTIVE: To evaluate the reported incidence, setting, and positional factors associated with shoulder and elbow injuries in high school and collegiate fast-pitch softball players. DATA SOURCES: PubMed, Ovid, Medline, EMBASE, Scopus, Cochrane Central, and Clinicaltrials.gov. STUDY SELECTION: English-language articles reporting the incidence of shoulder and/or elbow injuries occurring in high school or collegiate fast-pitch softball players were included. Biomechanical studies, review articles, abstract only texts, previous systematic reviews, and meta-analyses were excluded. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 4. DATA EXTRACTION: Two reviewers independently evaluated studies. Data related to the reported incidence of shoulder and elbow injuries, injury setting, position, and rate of return to play after injury were recorded. RESULTS: A total of 22 studies were identified. In high school athletes, shoulder injury rates ranged from 0.88 to 1.14 per 10,000 athletic exposures (AE), with elbow injury rates ranging from 0.41 to 0.71 per 10,000 AE. In collegiate athletes, reported injury rates ranged from 3.76 to 5.93 per 10,000 AE for shoulder and 1.5 to 3.39 per 10,000 AE for elbow injuries. Shoulder and elbow injuries were reported more commonly during competition in high school athletes, and with greater frequency in the practice setting in collegiate athletes. No association between injury incidence and position was appreciated at either the high school or collegiate level. Most (81%-96%) athletes were able to return to sport within 3 weeks of injury. CONCLUSION: The incidence of shoulder and elbow injuries was greater in collegiate softball athletes than in high school athletes.

Counterdiabatic Driving for Periodically Driven Systems.

Periodically driven systems have emerged as a useful technique to engineer the properties of quantum systems, and are in the process of being developed into a standard toolbox for quantum simulation. An outstanding challenge that leaves this toolbox incomplete is the manipulation of the states dressed by strong periodic drives. The state-of-the-art in Floquet control is the adiabatic change of parameters. Yet, this requires long protocols conflicting with the limited coherence times in experiments. To achieve fast control of nonequilibrium quantum matter, we generalize the notion of variational counterdiabatic driving away from equilibrium focusing on Floquet systems. We derive a nonperturbative variational principle to find local approximations to the adiabatic gauge potential for the effective Floquet Hamiltonian. It enables transitionless driving of Floquet eigenstates far away from the adiabatic regime. We discuss applications to two-level, Floquet band, and interacting periodically driven models. The developed technique allows us to capture nonperturbative photon resonances and obtain high-fidelity protocols that respect experimental limitations like the locality of the accessible control terms.

New Processes for Ionizing Nonvolatile Compounds in Mass Spectrometry: The Road of Discovery to Current State-of-the-Art.

This Perspective covers discovery and mechanistic aspects as well as initial applications of novel ionization processes for use in mass spectrometry that guided us in a series of subsequent discoveries, instrument developments, and commercialization. Vacuum matrix-assisted ionization on an intermediate pressure matrix-assisted laser desorption/ionization source without the use of a laser, high voltages, or any other added energy was simply unbelievable, at first. Individually and as a whole, the various discoveries and inventions started to paint, inter alia, an exciting new picture and outlook in mass spectrometry from which key developments grew that were at the time unimaginable, and continue to surprise us in its simplistic preeminence. We, and others, have demonstrated exceptional analytical utility. Our current research is focused on how best to understand, improve, and use these novel ionization processes through dedicated platforms and source developments. These ionization processes convert volatile and nonvolatile compounds from solid or liquid matrixes into gas-phase ions for analysis by mass spectrometry using, e.g., mass-selected fragmentation and ion mobility spectrometry to provide accurate, and sometimes improved, mass and drift time resolution. The combination of research and discoveries demonstrated multiple advantages of the new ionization processes and established the basis of the successes that lead to the Biemann Medal and this Perspective. How the new ionization processes relate to traditional ionization is also presented, as well as how these technologies can be utilized in tandem through instrument modification and implementation to increase coverage of complex materials through complementary strengths.

Prognostic Value of Echocardiographic Coupling Metrics in Systemic Sclerosis-Associated Pulmonary Vascular Disease.

BACKGROUND: Ineffective right ventricular (RV) adaptation to increasing pulmonary arterial (PA) afterload in pulmonary vascular disease (PVD) significantly contributes to morbidity and mortality. PVD in systemic sclerosis (SSc) arises through various mechanisms, yet detecting abnormal contractile response remains challenging. Here, we examine whether echocardiographic RV-PA coupling metrics correlate with invasive pressure-volume (PV) loops, enhancing the prediction of adverse clinical outcomes in SSc-PVD patients. METHODS: Prospectively enrolled patients with SSc-PVD with paired echocardiogram and PV loops were included. Linear regression and receiver-operating curve (ROC) analysis were used to assess the relationship between tricuspid annular plane systolic excursion (TAPSE)/PA systolic pressure (PASP), fractional area change (FAC)/PASP, tissue Doppler velocity (TDI S')/PASP, RV free wall strain (RVFWS)/PASP and coupling thresholds defined by end-systolic to end-arterial elastance (Ees/Ea), obtained by the multi-beat method. The contribution of right atrial strain (RAS) to RV-PA coupling parameters was also investigated. Kaplan-Meier analysis was used to identify the relationship between coupling ratios and composite outcomes including clinical worsening, lung transplant, and death. RESULTS: 42 patients with SSc were studied with mean age 59 ± 12 years, 91% female and varying degrees of PVD: mPAP 29.5 ± 12.8 mmHg, PVR 4.7 ± 4.2 WU, PCWP 10.3 ± 4.1 mmHg. Echocardiographic coupling metrics including TAPSE/PASP, FAC/PASP, TDI S'/PASP, RVFWSglobal and RVFWSbasal/PASP, and RASreservoir/PASP were linearly associated with Ees/Ea. At cut-points obtained through ROC analysis, all ratios were predictive of RV-PA uncoupling, defined by Ees/Ea, and composite outcomes. Additionally, RASreservoir/RVFWS correlated with Ees/Ea even after adjustment for PASP, suggesting that diminished RAS further impacts RV performance and coupling. CONCLUSION: Echocardiographic RV-PA coupling ratios strongly correlate with invasive Ees/Ea and predict adverse clinical outcomes in SSc patients across the spectrum of PVD. Further, we demonstrate how RAS impacts RV performance. These findings may refine risk stratification and prognostication in this at-risk cohort.

The McMaster Cough Severity Questionnaire (MCSQ): a cough severity instrument for patients with refractory chronic cough.

BACKGROUND: Cough severity represents an important endpoint to assess the impact of therapies for patients with refractory chronic cough (RCC). OBJECTIVE: To develop a new patient-reported outcome measure addressing cough severity in patients with RCC. METHODS: Phase 1 (item generation): A systematic survey, focus groups, and expert consultation generated 51 items. Phase 2 (item reduction): From a list of 51 items, 100 patients identified those they had experienced in the previous year and rated their importance on a 5-point scale. The MCSQ included items reported to occur most frequently and that had the highest importance scores. Patient feedback on the MCSQ led to elimination of redundant items. Another 100 patients completed the MCSQ, from which we performed an exploratory factor analysis and a Rasch analysis to further refine items on the MCSQ. RESULTS: Phase 2 led to selection of 15 items from the initial 51. Patient feedback on the 15 items led to elimination of 5 redundant items. An exploratory factor analysis of the 10-item MCSQ led to selection of two domains, elimination of one item that demonstrated cross-loading, and another that had high inter-item correlations. A Rasch analysis of the 8-item MCSQ confirmed that the response options functioned in a logically progressive manner and that no items exhibited differential item functioning. The final 8-item MCSQ has a one-week recall period and includes two domains (intensity and frequency). The 8-item MCSQ had high internal consistency (Cronbach's alpha, 0.89), proved able to distinguish different levels of cough severity (Pearson separation index, 0.89), and demonstrated high cross-sectional convergent validity (Pearson's correlation, 0.76 [95% CI 0.66 to 0.83]) with the 100-mm cough severity visual analogue scale. CONCLUSION: Initial evidence supports the validity of the MCSQ, an 8-item instrument measuring cough severity in patients with RCC. Future studies should evaluate its properties in measuring change over time.

Microwave Vertebrae Strength Probe Development: Robust and Fast Phase Unwrapping Technique.

We have developed a new transmission-based, open-ended coaxial probe for assessing vertebrae strength during spinal fusion surgery. The approach exploits the fact that the probes are within the far field of each other implying that the phase varies linearly with respect to propagation distance. Determining the absolute phase is critical for recovering the associated tissue dielectric properties from which bone strength will be determined. Unfortunately, unwanted multi-path signals corrupt the signals at the lower end of the operating frequency range from which our conventional unwrapping strategy depends. Our new approach requires only three measurements within the prime frequency range and can be determined robustly with a minimum of computations. This will be vital to developing a commercial device since the signal levels will be extremely low power requiring longer than usual data acquisition times, which will be mitigated by measuring the data at only a few frequencies. Fast and efficient operation will be critical for clinical success.

MULTISCALE ESTIMATION OF MORPHOMETRICITY FOR REVEALING NEUROANATOMICAL BASIS OF COGNITIVE TRAITS.

Morphometricity examines the global statistical association between brain morphology and an observable trait, and is defined as the proportion of the trait variation attributable to brain morphology. In this work, we propose an accurate morphometricity estimator based on the generalized random effects (GRE) model, and perform morphometricity analyses on five cognitive traits in an Alzheimer's study. Our empirical study shows that the proposed GRE model outperforms the widely used LME model on both simulation and real data. In addition, we extend morphometricity estimation from the whole brain to the focal-brain level, and examine and quantify both global and regional neuroanatomical signatures of the cognitive traits. Our global analysis reveals 1) a relatively strong anatomical basis for ADAS13, 2) intermediate ones for MMSE, CDRSB and FAQ, and 3) a relatively weak one for RAVLT.learning. The top associations identified from our regional morphometricity analysis include those between all five cognitive traits and multiple regions such as hippocampus, amygdala, and inferior lateral ventricles. As expected, the identified regional associations are weaker than the global ones. While the whole brain analysis is more powerful in identifying higher morphometricity, the regional analysis could localize the neuroanatomical signatures of the studied cognitive traits and thus provide valuable information in imaging and cognitive biomarker discovery for normal and/or disordered brain research.