Unlocking same-sign CPL: solvent effects on spectral form and racemisation kinetics in nine-coordinate chiral europium(III) complexes.

Understanding the factors that shape the circularly polarised luminescence (CPL) emission profiles of europium(III)-based CPL emitters to have specific sign properties, e. g. monosignate individual CPL transitions, is key to design novel complexes for applications ranging from advanced security inks to bio-probes for live cell imaging. In order to correlate structure and spectral characteristics, a photophysical and kinetic investigation has been conducted on a series of coordinatively saturated nine-coordinate europium(III) systems based on 1,4,7-triazacyclononane. We highlight that lanthanide emission is sensitive to changes in the ligand field by showing the linear dependence of total emission intensity ratios as a function of solvent polarity, for europium(III) complexes displaying an internal charge transfer (ICT) excited state. This sensitivity increases by a factor of 20 when studying changes in CPL spectra, rendering these complexes accurate probes of local polarity. Solvent polarity, solvent-specific effects, and the nature of the chromophores' coordinating donor atoms strongly influence the kinetic stability of europium(III) complexes with respect to enantiomer interconversion. Notably, we show that the choice of donor groups to coordinating to europium(III) and the nature and polarity of the solvent affects the rate of racemisation, leading to systems with very long half-lives at room temperature in non-polar media.

Enlarged pituitary gland volume: a possible state rather than trait marker of psychotic disorders.

BACKGROUND: Enlarged pituitary gland volume could be a marker of psychotic disorders. However, previous studies report conflicting results. To better understand the role of the pituitary gland in psychosis, we examined a large transdiagnostic sample of individuals with psychotic disorders. METHODS: The study included 751 participants (174 with schizophrenia, 114 with schizoaffective disorder, 167 with psychotic bipolar disorder, and 296 healthy controls) across six sites in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium. Structural magnetic resonance images were obtained, and pituitary gland volumes were measured using the MAGeT brain algorithm. Linear mixed models examined between-group differences with controls and among patient subgroups based on diagnosis, as well as how pituitary volumes were associated with symptom severity, cognitive function, antipsychotic dose, and illness duration. RESULTS: Mean pituitary gland volume did not significantly differ between patients and controls. No significant effect of diagnosis was observed. Larger pituitary gland volume was associated with greater symptom severity (F = 13.61, p = 0.0002), lower cognitive function (F = 4.76, p = 0.03), and higher antipsychotic dose (F = 5.20, p = 0.02). Illness duration was not significantly associated with pituitary gland volume. When all variables were considered, only symptom severity significantly predicted pituitary gland volume (F = 7.54, p = 0.006). CONCLUSIONS: Although pituitary volumes were not increased in psychotic disorders, larger size may be a marker associated with more severe symptoms in the progression of psychosis. This finding helps clarify previous inconsistent reports and highlights the need for further research into pituitary gland-related factors in individuals with psychosis.

Multiphoton Ionization/Dissociation of Molecular Sulfur S2 in the UV Region.

The multiphoton ionization/dissociation dynamics of molecular sulfur (S2) in the ultraviolet range of 205-300 nm is studied using velocity map ion imaging (VMI). In this one-color experiment, molecular sulfur (S2) is generated in a pulsed discharge and then photodissociated by UV radiation. At the three-photon level, superexcited states are accessed via two different resonant states: the B3Σu- (v' = 8-11) valence states at the one-photon level and a Rydberg state at the two-photon level. Among the decay processes of these superexcited states, dissociation to electronically excited S atoms is dominant as compared to autoionization to ionic states S2+ (X2Πg) at wavelengths λ < 288 nm. The anisotropy parameter extracted from these images reflects the parallel character of these electronic transitions. In contrast, autoionization is found to be particularly efficient at S(1D) and S(1S) detection wavelengths around 288 nm. Information obtained from the kinetic energy distributions of S atoms has revealed the existence of vibrationally excited S2+ (X2Πg (v+ > 11)) that dissociates to ionic products following one-photon absorption. This work also reveals many interesting features of S2 photodynamics compared to those of electronically analogous O2.

Knowledge, attitudes and practices regarding respirable silica exposure and personal protective equipment use among brick kiln workers in Nepal.

OBJECTIVES: Brick kiln workers in Nepal are a neglected population who are exposed to high respirable silica concentrations, and few use interventions to reduce exposure. We aimed to characterise the prevalence of respiratory personal protective equipment (PPE) use, understand knowledge and attitudes towards kiln dust and respiratory PPE and identify factors associated with respiratory PPE use. METHODS: We conducted a cross-sectional study in Bhaktapur, Nepal. We used simple random selection to identify 10 out of 64 total kilns and stratified random sampling of 30 households to enrol workers aged ≥14 years within selected kilns. Field workers surveyed participants using structured questionnaires. Our primary outcome was to characterise the prevalence of current respiratory PPE use and secondary outcomes were summaries of knowledge, attitudes and practice of PPE use. RESULTS: We surveyed 83 workers (mean age 30.8 years, 77.1% male). Of these, 28.9% reported current respiratory PPE use at work, 3.6% heard of silicosis prior to the survey and 24.1% correctly identified the best respiratory PPE (N95, compared with surgical masks and barrier face coverings) for reducing dust exposure. Respiratory PPE users had higher income (mean monthly household income US$206 vs US$145; p=0.04) and education levels (25% vs 5.1% completed more than primary school; p=0.02) compared with non-users. CONCLUSIONS: Respiratory PPE use was low. Workers had poor knowledge of kiln dust health effects and proper respiratory PPE. We highlight important barriers to PPE use, particularly knowledge gaps, which can guide future investigations to reduce the silicosis burden among brick kiln workers.

Brick kiln pollution and its impact on health: A systematic review and meta-analysis.

Brick kiln emissions adversely affect air pollution and the health of workers and individuals living near the kilns; however, evidence of their impacts remains limited. We conducted a systematic review of brick kiln pollution (emissions, source contributions and personal exposures) and its effects on health. We extracted articles from electronic databases and through manual citation searching. We estimated pooled, sample-size-weighted means and standard deviations for personal exposures by job type; computed mean emission factors and pollutant concentrations by brick kiln design; and meta-analyzed differences in means or proportions for health outcomes between brick kiln workers and controls or for participants living near or far away from kilns. We identified 104 studies; 74 were conducted in South Asia. The most evaluated pollutants were particulate matter (PM; n = 48), sulfur dioxide (SO2; n = 24) and carbon monoxide (CO; n = 22), and the most evaluated health outcomes were respiratory health (n = 34) and musculoskeletal disorders (n = 9). PM and CO emissions were higher among traditional than improved brick kilns. Mean respirable silica exposures were only measured in 4 (4%) studies and were as high as 620 µg/m3, exceeding the NIOSH recommended exposure limit by a factor of over 12. Brick kiln workers had consistently worse lung function, more respiratory symptoms, more musculoskeletal complaints, and more inflammation when compared to unexposed participants across studies; however, most studies had a small sample size and did not fully describe methods used for sampling or data collection. On average, brick kiln workers had worse health outcomes when compared to unexposed controls but study quality supporting the evidence was low. Few studies reported silica concentrations or personal exposures, but the few that did suggest that exposures are high. Further research is needed to better understand the relationship between brick kiln pollution and health among workers, and to evaluate exposure mitigation strategies.

Examining emergency department utilization following bariatric surgery.

BACKGROUND: Emergency department (ED) utilization following surgery is poorly understood and places immense strain on the healthcare system, being responsible for up to $38 billion in wasteful spending annually. The aim of this study was to quantify ED utilization following bariatric procedures to identify causes and areas of improvement. MATERIALS AND METHODS: A retrospective review of a prospectively maintained database was conducted for all patients who underwent metabolic bariatric surgery (MBS) between November 2006 and June 2019. The study includes 4703 patients across 8 hospitals in a single health system. Patients who returned to the ED within 30 and 90 days were analyzed for relation to surgery and preventability. RESULTS: Of the 4703 patients that underwent MBS, 907 (19.3%) visited the ED at least once within 90 days and 350 (7.4%) required hospital readmission. The most common bariatric procedure performed was the Roux-en-Y Gastric Bypass (RYGB) (3716/4703) with an average BMI of 43.8. The median length between discharge and ED visit was 19 days. Under 50% of patients called prior to ED presentation and 61% of these ED visits resulted in discharge. CONCLUSION: While hospital readmissions following MBS have been scrutinized in literature, investigation of ED utilization remains scarce. Our study is one of few to investigate postoperative ED utilization up to 90 days following bariatric intervention. A clear opportunity exists to improve discharge education and early post-discharge communication. This would additionally alleviate burden to allow focus on the acutely ill.

Vibrational state-specific nonadiabatic photodissociation dynamics of OCS+ via A2Π1/2 (ν1 0 ν3) states.

The identification and analysis of quantum state-specific effects can significantly deepen our understanding of detailed photodissociation dynamics. Here, we report an experimental investigation on the vibrational state-mediated photodissociation of the OCS+ cation via the A2Π1/2 (ν1 0 ν3) states by using the velocity map ion imaging technique over the photolysis wavelength range of 263-294 nm. It was found that the electronically excited S+ product channel S+(2Du) + CO (X1Σ+) was significantly enhanced when the ν1 and ν3 vibrational modes were excited. Clear deviations in the branching ratios of the electronically excited S+ channel were observed when the vibrational modes ν1 and ν3 were selectively excited. The results reveal that vibrationally excited states play a vital role in influencing the nonadiabatic couplings in the photodissociation process.

Large multiplanar changes to native alignment have no apparent impact on clinical outcomes following total knee arthroplasty.

PURPOSE: This study sought to examine if achieved postoperative alignment when compared to the native anatomy would lead to a difference in Patient Reported Outcome Measures (PROMs), and whether the achieved alignment could be broadly categorised by an accepted alignment strategy. METHODS: A retrospective cohort study of prospectively collected data on patients undergoing single primary or bilateral simultaneous total knee arthroplasty (TKA) was carried out. CT scans were used to determine the mean change ("delta values") between the pre and postoperative; hip-knee-ankle angle, lateral distal femoral angle, medial proximal tibial angle and femoral implant rotation. Femoral implant flexion and tibial implant slope were measured postoperatively. The primary outcome was the relationship of the variables to the change in KOOS pain subscale after one year. The secondary outcome was the number of knees which could be categorised postoperatively to an alignment strategy, and the mean PROMs in each cohort. RESULTS: A total of 296 knees in 261 patients were available for analysis. With regards to the primary outcome, the delta values for each variable did not demonstrate any association with the change in knee injury and osteoarthritis outcome score (KOOS) pain score. Approximately 46% of knees could not be categorised to an alignment strategy based on postoperatively measured alignment, with no significant difference between each cohort with regards to the change in KOOS Pain score. CONCLUSION: Achieved alignment does not consistently match accepted alignment strategies, and appears to confer no benefit to clinical outcomes when the native anatomy is most closely approximated, nor results in poorer outcomes in outliers. This study highlights the importance of routine three dimensional pre and postoperative imaging in clinical practice and for the valid analysis of outcomes in studies on alignment. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Lateral extra-articular tenodesis does not enhance ACL graft healing, however, does reduce graft tunnel widening.

PURPOSE: The study hypothesized that the addition of lateral extra-articular tenodesis (LEAT) in anterior cruciate ligament reconstruction (ACLR) had a significant effect on ACL graft healing. METHODS: A total of 80 patients were divided into two cohorts matched for gender, age, body mass index, time from surgery to post-operative MRI and graft diameter. Forty patients underwent ACL reconstruction alone, while 40 underwent ACLR in addition to LEAT. Patients underwent a magnetic resonance imaging scan at 12 months post-surgery; tunnel apertures were measured using multiplanar reformation, graft healing was assessed using signal-to-noise quotient (SNQ) in three regions of interest and finally graft maturity and integration were classified using the Howell and Ge scale, respectively. In addition, clinical evaluation and patient-reported outcome measures were collected. RESULTS: The mean femoral tunnel widening at 12 months post-surgery was 39.8 ± 14.0% in the ACLR + LEAT group and 55.2 ± 12.7% in the ACLR alone group (p < 0.05). The mean tibial tunnel widening was 29.3 ± 12.7% in the ACLR + LEAT group and 44.4 ± 12.1% in the ACLR group (p < 0.05). The mean adjusted graft SNQ was 9.0 ± 14.9 in the ACLR + LEAT group and 9.5 ± 11.4 in the ACLR group (n.s.). CONCLUSION: At 1 year post-operatively, we noted significantly less femoral and tibial tunnel widening in the ACLR + LEAT group. LEAT did not result in a statistically significant effect on graft healing. LEVEL OF EVIDENCE: Level III.

Imaging rotational energy transfer: comparative stereodynamics in CO + N2 and CO + CO inelastic scattering.

State-to-state rotational energy transfer in collisions of ground ro-vibrational state 13CO molecules with N2 molecules has been studied using the crossed molecular beam method under kinematically equivalent conditions used for 13CO + CO rotationally inelastic scattering described in a previously published report (Sun et al., Science, 2020, 369, 307-309). The collisionally excited 13CO molecule products are detected by the same (1 + 1' + 1'') VUV (Vacuum Ultra-Violet) resonance enhanced multiphoton ionization scheme coupled with velocity map ion imaging. We present differential cross sections and scattering angle resolved rotational angular momentum alignment moments extracted from experimentally measured 13CO + N2 scattering images and compare them with theoretical predictions from quasi-classical trajectories (QCT) on a newly calculated 13CO-N2 potential energy surface (PES). Good agreement between experiment and theory is found, which confirms the accuracy of the 13CO-N2 potential energy surface for the 1460 cm-1 collision energy studied by experiment. Experimental results for 13CO + N2 are compared with those for 13CO + CO collisions. The angle-resolved product rotational angular momentum alignment moments for the two scattering systems are very similar, which indicates that the collision induced alignment dynamics observed for both systems are dominated by a hard-shell nature. However, compared to the 13CO + CO measurements, the primary rainbow maximum in the DCSs for 13CO + N2 is peaked consistently at more backward scattering angles and the secondary maximum becomes much less obvious, implying that the 13CO-N2 PES is less anisotropic. In addition, a forward scattering component with high rotational excitation seen for 13CO + CO does not appear for 13CO-N2 in the experiment and is not predicted by QCT theory. Some of these differences in collision dynamics behaviour can be predicted by a comparison between the properties of the PESs for the two systems. More specific behaviour is also predicted from analysis of the dependence on the relative collision geometry of 13CO + N2 trajectories compared to 13CO + CO trajectories, which shows the special 'do-si-do' pathway invoked for 13CO + CO is not effective for 13CO + N2 collisions.

Disentangling Multiphoton Ionization and Dissociation Channels in Molecular Oxygen Using Photoelectron-Photoion Coincidence Imaging.

Multiphoton excitation of molecular oxygen in the 392-408 nm region is studied using a tunable femtosecond laser coupled with a double velocity map imaging photoelectron-photoion coincidence spectrometer. The laser intensity is held at ≤∼1 TW/cm2 to ensure excitation in the perturbative regime, where the possibility of resonance enhanced multiphoton ionization (REMPI) can be investigated. O2+ production is found to be resonance enhanced around 400 nm via three-photon excitation to the e'3Δu(v = 0) state, similar to results from REMPI studies using nanosecond dye lasers. O+ production reaches 7% of the total ion yield around 405 nm due to two processes: autoionization following five-photon excitation of O2, producing O2+(X(v)) in a wide range of vibrational states followed by two- or three-photon dissociation, or six-photon excitation to a superexcited O2** state followed by neutral dissociation and subsequent ionization of the electronically excited O atom. Coincidence detection is shown to be crucial in identifying these competing pathways.

Towards a validated musculoskeletal knee model to estimate tibiofemoral kinematics and ligament strains: comparison of different anterolateral augmentation procedures combined with isolated ACL reconstructions.

BACKGROUND: Isolated ACL reconstructions (ACLR) demonstrate limitations in restoring native knee kinematics. This study investigates the knee mechanics of ACLR plus various anterolateral augmentations using a patient-specific musculoskeletal knee model. MATERIALS AND METHODS: A patient-specific knee model was developed in OpenSim using contact surfaces and ligament details derived from MRI and CT data. The contact geometry and ligament parameters were varied until the predicted knee angles for intact and ACL-sectioned models were validated against cadaveric test data for that same specimen. Musculoskeletal models of the ACLR combined with various anterolateral augmentations were then simulated. Knee angles were compared between these reconstruction models to determine which technique best matched the intact kinematics. Also, ligament strains calculated by the validated knee model were compared to those of the OpenSim model driven by experimental data. The accuracy of the results was assessed by calculating the normalised RMS error (NRMSE); an NRMSE < 30% was considered acceptable. RESULTS: All rotations and translations predicted by the knee model were acceptable when compared to the cadaveric data (NRMSE < 30%), except for the anterior/posterior translation (NRMSE > 60%). Similar errors were observed between ACL strain results (NRMSE > 60%). Other ligament comparisons were acceptable. All ACLR plus anterolateral augmentation models restored kinematics toward the intact state, with ACLR plus anterolateral ligament reconstruction (ACLR + ALLR) achieving the best match and the greatest strain reduction in ACL, PCL, MCL, and DMCL. CONCLUSION: The intact and ACL-sectioned models were validated against cadaveric experimental results for all rotations. It is acknowledged that the validation criteria are very lenient; further refinement is required for improved validation. The results indicate that anterolateral augmentation moves the kinematics closer to the intact knee state; combined ACLR and ALLR provide the best outcome for this specimen.

Laparoscopic revision paraesophageal hernia repair: a 16-year experience at a single institution.

BACKGROUND: Laparoscopic paraesophageal hernia repair (PEHr) is a safe and effective procedure for relieving foregut symptoms associated with paraesophageal hernias (PEH). Nonetheless, it is estimated that about 30-50% of patients will have symptomatic recurrence requiring additional surgical intervention. Revision surgery is technically demanding and may be associated with a higher rate of morbidity and poor patient-reported outcomes. We present the largest study of perioperative and quality-of-life outcomes among patients who underwent laparoscopic revision PEHr. METHODS: A retrospective review of all patients who underwent laparoscopic revision paraesophageal hernia repair between February 2003 and October 2019, at a single institution was conducted. All revisions of Type I hiatal hernias were excluded. The following validated surveys were used to evaluate quality-of-life outcomes: Reflux Symptom Index (RSI) and Gastroesophageal Reflux Disease Health-Related QOL (GERD-HRQL). Patient demographic, perioperative, and quality-of-life (QOL) data were analyzed using univariate analysis. RESULTS: One hundred ninety patients were included in the final analysis (63.2% female, 90.5% single revision, 9.5% multiple revisions) with a mean age, BMI, and age-adjusted Charlson score of 56.6 ± 14.7 years, 29.7 ± 5.7 kg/m2, and 2.04 ± 1.9, respectively. The study cohort consisted of type II (49.5%), III (46.3%), and IV hiatal hernia (4.2%), respectively. Most patients underwent either a complete (68.7%) or partial (27.7%) fundoplication. A Collis gastroplasty was performed in 14.7% of patients. The median follow-up was 17.6 months. The overall morbidity and mortality rate were 15.8% and 1.1%, respectively. The 30-day readmission rate was 9.5%. Additionally, at latest follow-up 47.9% remained on antireflux medication. At latest follow-up, there was significant improvement in mean RSI score (46.4%, p < 0.001) from baseline within the study population. Furthermore, there was no significant difference in QOL between patients who had a history of an initial repair only or history of revision surgery at latest review. The overall recurrence rate was 16.3% with 6.3% requiring a surgical revision. CONCLUSION: Laparoscopic revision PEHr is associated with a low rate of morbidity and mortality. Revision surgery may provide improvement in QOL outcomes, despite the high rate of long-term antireflux medication use. The rate of recurrent paraesophageal hernia remains low with few patients requiring a second revision. However, longer follow-up is needed to better characterize the long-term recurrence rate and symptomatic improvements.

Revision paraesophageal hernia repair outcomes in patients with typical and atypical reflux.

BACKGROUND: Revision laparoscopic anti-reflux surgery (RLARS) is effective in alleviating the typical symptoms of gastroesophageal reflux disease (GERD). RLARS outcomes in patients with atypical GERD symptoms has not been well established. A composite Reflux Symptom Index (RSI) score greater than 13 indicates extraesophageal manifestation of pathological reflux. In this study, we analyzed the differences in quality-of-life (QOL) and perioperative outcomes between patients with atypical versus typical GERD who underwent RLARS. METHODS: A retrospective review was conducted of a prospectively maintained database of patients with pathologic reflux who underwent RLARS from February 2003 to October 2019. The cohort was divided into two groups, those with typical versus atypical manifestations of GERD, as defined by their RSI score. Patients with a RSI score of  > 13 were assigned to the Atypical group and those ≤ 13 were assigned to the Typical group. Patient QOL outcomes were prospectively followed using the RSI survey. Significance was defined by p-value less than 0.05. RESULTS: A total of 133 patients (Typical 61, Atypical 72) were included in the final analysis. The two groups were similar (p > 0.05) in mean age (58.1 ± 13.3 vs. 55.3 ± 15.5 years), body mass index (29.6 ± 5.0 vs. 30.3 ± 5.4), female sex distribution (60.7% vs. 59.7%) and age adjusted Charlson score (1.76 ± 1.58 vs. 1.98 ± 1.94). The Typical group had a higher frequency of type III hiatal hernia (62.3% vs. 29.2%) and Collis gastroplasty (29.5% vs. 5.6%). The groups had similar rates of partial and complete fundoplication with similar median length of stay (Typical: 3.0 ± 3.4 days vs. Atypical: 2.4 ± 1.7 days). After a mean follow-up of 30.2 ± 33.6 months, both groups reported similar rates of improvement in RSI outcome from baseline (58.1% vs 43.3%, p = .149). However, the RSI outcome at the latest follow-up for the Typical group was significantly better than the Atypical group after RLARS (2.8 ± 5.3 vs. 15.9 ± 11.1, respectively). CONCLUSION: Patients who undergo revision paraesophageal hernia repair with objective findings of GERD and subjective complaints of atypical reflux symptoms may show long-term improvement in QOL outcomes. However, these results are contingent on proper patient selection and a thorough work-up for pathological reflux in this population. Further research is needed to determine universal diagnostic criteria to assist in the early detection and surgical treatment of patients with atypical GERD.

Clinical and financial outcomes of per-oral endoscopic myotomy compared to laparoscopic heller myotomy for treatment of achalasia.

BACKGROUND: Previous studies analyzing short-term outcomes for per-oral endoscopic myotomy (POEM) have shown excellent clinical response rates and shorter operative times compared to laparoscopic Heller myotomy (LHM). Despite this, many payors have been slow to recognize POEM as a valid treatment option. Furthermore, comparative studies analyzing long-term outcomes are limited. This study compares perioperative and long-term outcomes, cost-effectiveness, and reimbursement for POEM and LHM at a single institution. METHODS: Adult patients who underwent POEM or LHM between 2014 and 2021 and had complete preoperative data with at least one complete follow up, were retrospectively analyzed. Demographic data, success rate, operative time, myotomy length, length of stay, pre- and postoperative symptom scores, anti-reflux medication use, cost and reimbursement were compared. RESULTS: 58 patients met inclusion with 25 undergoing LHM and 33 undergoing POEM. There were no significant differences in preoperative characteristics. Treatment success (Eckardt ≤ 3) for POEM and LHM was achieved by 88% and 76% of patients, respectively (p = 0.302). POEM patients had a shorter median operative time (106 min. vs. 145 min., p = 0.003) and longer median myotomy length (11 cm vs. 8 cm, p < 0.001). All LHM patients had a length of stay (LOS) ≥ 1 day vs. 51.5% for POEM patients (p < 0.001). Both groups showed improvements in dysphagia, heartburn, regurgitation, Eckardt score, GERD HRQL, RSI, and anti-reflux medication use. The improvement in dysphagia score was greater in patients undergoing POEM (2.30 vs 1.12, p = 0.003). Median hospital reimbursement was dramatically less for POEM ($3,658 vs. $14,152, p = 0.002), despite median hospital costs being significantly lower compared to LHM ($2,420 vs. $3,132, p = 0.029). RESULTS: POEM is associated with a shorter operative time and LOS, longer myotomy length, and greater resolution of dysphagia compared to LHM. POEM costs are significantly less than LHM but is poorly reimbursed.

Deep psychophysiological phenotyping of adolescents and adults with 22q11.2 deletion syndrome: a multilevel approach to defining core disease processes.

BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal interstitial-deletion disorder, occurring in approximately 1 in 2000 to 6000 live births. Affected individuals exhibit variable clinical phenotypes that can include velopharyngeal anomalies, heart defects, T-cell-related immune deficits, dysmorphic facial features, neurodevelopmental disorders, including autism, early cognitive decline, schizophrenia, and other psychiatric disorders. Developing comprehensive treatments for 22q11.2DS requires an understanding of both the psychophysiological and neural mechanisms driving clinical outcomes. Our project probes the core psychophysiological abnormalities of 22q11.2DS in parallel with molecular studies of stem cell-derived neurons to unravel the basic mechanisms and pathophysiology of 22q11.2-related psychiatric disorders, with a primary focus on psychotic disorders. Our study is guided by the central hypothesis that abnormal neural processing associates with psychophysiological processing and underlies clinical diagnosis and symptomatology. Here, we present the scientific background and justification for our study, sharing details of our study design and human data collection protocol. METHODS: Our study is recruiting individuals with 22q11.2DS and healthy comparison subjects between the ages of 16 and 60 years. We are employing an extensive psychophysiological assessment battery (e.g., EEG, evoked potential measures, and acoustic startle) to assess fundamental sensory detection, attention, and reactivity. To complement these unbiased measures of cognitive processing, we will develop stem-cell derived neurons and examine neuronal phenotypes relevant to neurotransmission. Clinical characterization of our 22q11.2DS and control participants relies on diagnostic and research domain criteria assessments, including standard Axis-I diagnostic and neurocognitive measures, following from the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and the North American Prodrome Longitudinal Study (NAPLS) batteries. We are also collecting measures of autism spectrum (ASD) and attention deficit/hyperactivity disorder (ADHD)-related symptoms. DISCUSSION: Studying 22q11.2DS in adolescence and adulthood via deep phenotyping across multiple clinical and biological domains may significantly increase our knowledge of its core disease processes. Our manuscript describes our ongoing study's protocol in detail. These paradigms could be adapted by clinical researchers studying 22q11.2DS, other CNV/single gene disorders, or idiopathic psychiatric syndromes, as well as by basic researchers who plan to incorporate biobehavioral outcome measures into their studies of 22q11.2DS.

Vacuum ultraviolet photodissociation dynamics of OCS via the F Rydberg state: The O (3PJ=2,1,0) product channels.

We study the vacuum ultraviolet (VUV) photodissociation dynamics of carbonyl sulfide (OCS) by using the time sliced velocity map ion imaging technique. Experimental images of the dissociative O (3PJ=0,1,2) products were acquired at five VUV photolysis wavelengths from 133.26 to 139.96 nm that correspond to the F Rydberg state of OCS. High vibrational states of the carbon monosulfide (CS) co-products are partially resolved in the images. The product total kinetic energy releases, angular distributions, and the product state branching ratios were derived from the experimental images. Notably, it is found that the anisotropic parameters change systematically with the photolysis wavelength. The anisotropic parameters and the product state branching ratios are significantly sensitive to the J quantum number of the O (3PJ) products. The phenomenon indicates that multiple nonadiabatic pathways are strongly involved in the photodissociation processes.

svMorph: Interactive Geometry-Editing Tools for Virtual Patient-Specific Vascular Anatomies.

We propose svMorph, a framework for interactive virtual sculpting of patient-specific vascular anatomic models. Our framework includes three tools for the creation of tortuosity, aneurysms, and stenoses in tubular vascular geometries. These shape edits are performed via geometric operations on the surface mesh and vessel centerline curves of the input model. The tortuosity tool also uses the physics-based Oriented Particles method, coupled with linear blend skinning, to achieve smooth, elastic-like deformations. Our tools can be applied separately or in combination to produce simulation-suitable morphed models. They are also compatible with popular vascular modeling software, such as simvascular. To illustrate our tools, we morph several image-based, patient-specific models to create a range of shape changes and simulate the resulting hemodynamics via three-dimensional, computational fluid dynamics. We also demonstrate the ability to quickly estimate the hemodynamic effects of the shape changes via the automated generation of associated zero-dimensional lumped-parameter models.

Patient-reported impairment following TKA is reduced when a computationally simulated predicted ideal alignment is achieved.

PURPOSE: Joint dynamics following Total Knee Arthroplasty (TKA) may influence patient-reported outcome. Simulations allow many knee alignment approaches to a single patient to be considered prior to surgery. The simulated kinematics can be matched to patient-reported outcome to predict kinematic patterns most likely to give the best outcome. This study aims to validate one such previously developed algorithm based on a simulated deep knee bend (the Dynamic Knee Score, DKS). METHODS: 1074 TKA patients with pre- and post-operative Computerised Tomography (CT) scans and 12-month post-operative Knee Injury and Osteoarthritis Outcomes (KOOS) Scores were identified from the 360 Med Care Joint Registry. Landmarking and registration of implant position was performed on all CT scans, and each of the achieved TKAs was computationally simulated and received a predictive outcome score from the DKS. In addition, a set of potential alternative surgical plans which might have been followed were simulated. Comparison of patient-reported issues and DKS score was evaluated in a counter-factual study design. RESULTS: Patient-reported impairment with the knee catching and squatting was shown to be 30% lower (p = 0.005) and 22% lower (p = 0.026) in patients where the best possible DKS result was the one surgically achieved. Similar findings were found relating attainment of the best tibial slope and posterior femoral resection DKS plans to patient-reported difficulty straightening the knee (40% less likely, p < 0.001) and descending stairs (35% less likely, p = 0.006). CONCLUSION: The DKS has been shown to correlate with presence of patient-reported impairments post-TKA and the resultant algorithm can be applied in a pre-operative planning setting. Outcome optimization in the future may come from patient-specific selection of an alignment strategy and simulations may be a technological enabler of this trend. LEVEL OF EVIDENCE: III (Retrospective Cohort Study).

Triggered Functional Dynamics of AsLOV2 by Time-Resolved Electron Paramagnetic Resonance at High Magnetic Fields.

We present time-resolved Gd-Gd electron paramagnetic resonance (TiGGER) at 240 GHz for tracking inter-residue distances during a protein's mechanical cycle in the solution state. TiGGER makes use of Gd-sTPATCN spin labels, whose favorable qualities include a spin-7/2 EPR-active center, short linker, narrow intrinsic linewidth, and virtually no anisotropy at high fields (8.6 T) when compared to nitroxide spin labels. Using TiGGER, we determined that upon light activation, the C-terminus and N-terminus of AsLOV2 separate in less than 1 s and relax back to equilibrium with a time constant of approximately 60 s. TiGGER revealed that the light-activated long-range mechanical motion is slowed in the Q513A variant of AsLOV2 and is correlated to the similarly slowed relaxation of the optically excited chromophore as described in recent literature. TiGGER has the potential to valuably complement existing methods for the study of triggered functional dynamics in proteins.