Craniofacial Imaging of Pediatric Patients by Ultrashort Echo-Time Bone-Selective MRI in Comparison to CT.

RATIONALE AND OBJECTIVES: The emergence of low-dose protocols for CT imaging has mitigated pediatric radiation exposure, yet ionizing radiation remains a concern for children with complex craniofacial conditions requiring repeated radiologic monitoring. In this work, the clinical feasibility of an ultrashort echo time (UTE) MRI sequence was investigated in pediatric patients. MATERIALS AND METHODS: Twelve pediatric patients (6 female, age range 8 to 18 years) with various imaging conditions were scanned at 3T using a dual-radiofrequency, dual-echo UTE MRI sequence. Bright-bone images were generated using a weighted least-squares conjugate gradient method to enhance bone specificity. The overlap of the binary skull masks was quantified using the Dice similarity coefficient (DSC) and the 95th percentile Hausdorff distance (HD95) to evaluate the similarity between MRI and CT. To assess the anatomic accuracy of 3D skull reconstructions, six craniometric distances were recorded and the agreement between MRI- and CT-derived measurements was evaluated using Lin's concordance correlation coefficient (ρc). RESULTS: The bright-bone images from UTE MRI demonstrated high bone-contrast, suppression of soft tissue, and separation from air at the sinuses. The DSC and HD95 between MRI and CT had medians of 0.81 ± 0.10 and 1.87 ± 0.32 mm, respectively. There was good agreement between MRI and CT for all craniometric distances (ρc ranging from 0.90 to 0.99) with a mean absolute difference in measurements of < 2 mm. CONCLUSION: The clinical feasibility of the UTE MRI sequence for craniofacial imaging was demonstrated in a cohort of pediatric patients, showing good agreement with CT in resolving thin bone structures and craniometry.

Comparing Current and Future Land Suitability for Growing Rainfed Corn (Zea mays) in Georgia, USA.

Land suitability (LS) classifications are essential for efficient and sustainable agricultural land use. With climate change, future LS classifications are necessary to ensure that crop growth remains sustainable and prevents land degradation. This study develops a current LS classification for rainfed corn (Zea mays) growth in the state of Georgia, USA, which is validated using historical census data on yield, acres planted, and corn crop lost. Significant (p < 0.05) differences were found between yield, acres planted, and crop loss percentage across LS classes for many years. Soil factors (Ph and soil texture) showed significant differences in fewer years compared to climate and topography factors, as soil factors can be altered by management practices such as liming and irrigation. Future LS classes determined by climate factors indicated a shift to the northwest of 150-300 km by the year 2100 based on the RCP4.5 or RCP8.5 emissions scenarios. The northwards shift in more suitable land due to rising maximum temperatures is expected to limit rainfed corn growth in Georgia in the future. As urban areas become more suitable for corn growth, farmers may need to plant crops earlier, irrigate, or switch to different crops. These results have important implications for agricultural planning and policy in the state of Georgia.

Long-term photogrammetric outcomes of midface advancement in Apert syndrome: are we nearing normal?

BACKGROUND: The aesthetic goals of midface surgery in Apert syndrome are to correct the multi-planar midface deficiency and normalize facial ratios. This study characterizes the long-term photogrammetric outcomes of midface advancement in Apert syndrome. METHODS: Patients with Apert syndrome who underwent midface distraction from 2000 to 2023 were retrospectively reviewed. Soft tissue measurements were applied to preoperative (T0), short-term postoperative (T1), and long-term postoperative (T2) photographs. Long-term changes were compared between subcranial and transcranial procedures, segmental and non-segmental osteotomies, and individual techniques. Frontal facial dimensions at time T2 were compared to age- and sex-matched normal controls from the NIMH-ChEFS face database. RESULTS: Twenty patients had postoperative follow-up of T1 = 0.6 ± 0.4 and T2 = 4.7 ± 1.1 years and were compared to 40 normal controls. From time T0 to T2, middle facial third height increased (26.1 ± 3.0% to 27.8 ± 2.6%, p = 0.026), canthal tilt improved (- 7.6° ± 3.7° to - 3.9° ± 4.4°, p < 0.001), and facial convexity increased (182.9° ± 6.2° to 167.9° ± 8.6°, p < 0.001). From time T1 to T2, facial convexity flattened (159.4° ± 10.1° to 167.9° ± 8.6°, p < 0.001). Compared to controls, patients at time T2 had shorter middle facial third height (27.8 ± 2.6% vs. 32.0 ± 1.9%, p < 0.001) and reverse canthal tilt (- 3.9° ± 4.4° vs. 5.4° ± 2.6°, p < 0.001). CONCLUSIONS: A tailored treatment approach to the Apert midface yields varying degrees of resolution of central midfacial shortening, canthal tilt, and facial concavity at 5 years postoperatively. A slight reduction in facial convexity over time, likely reflecting pseudorelapse in the setting of sagittal overcorrection, should be anticipated. Greater utilization of segmental osteotomies may bring facial third ratios and canthal tilt closer to normal morphometric values.

Nutrition practices in Australia and New Zealand in response to evolving evidence: Results of three point-prevalence audits.

BACKGROUND: The Augmented versus Routine Approach to Giving Energy Trial (TARGET) was a 4000-patient trial in which augmented enteral calorie dose did not influence outcomes. AIM: We aimed to quantify practice change following TARGET. METHODS: Three single-day, prospective, multicentre, point-prevalence audits of adult patients receiving enteral nutrition (EN) in participating Australian and New Zealand intensive care units at 10:00 AM were conducted: (i) 2010 (before conducting TARGET); (ii) 2018 (immediately before publishing TARGET results); and (iii) 2020 (2 years after TARGET publication). Data included baseline characteristics, clinical outcomes, and nutrition data. Data are n (%), mean ± standard deviation, or median [interquartile range]. Differences in enteral calorie prescription between 2018 and 2020 were compared using the Mann-Whitney test. RESULTS: The percentage of patients receiving EN (2010 42%, 2018 38%, 2020 33%; P = 0.012) and the prescription of calorie-dense EN formula (≥1.5 kcal/ml) (2010 33%, 2018 24%, 2020 23%; P = 0.038) decreased over time. However, when comparing prepublication and postpublication (2018-2020), calorie dose and calorie density were similar: 22.9 ± 8.6 versus 23.4 ± 12.8 kcal/kg/day (P = 0.816) and <1.5 kcal/ml: 76 versus 77% (P = 0.650), respectively. CONCLUSION: In Australian and New Zealand intensive care units, enteral calorie dose and calorie density of prescribed EN were similar before TARGET publication and 2 years later.

Changes in Ventricular Volume After Posterior Vault Distraction Osteogenesis in Patients With Syndromic and Nonsyndromic Craniosynostosis.

OBJECTIVE: Little is known about the response of the ventricular system to cranial vault surgery in patients with craniosynostosis. This study aims to evaluate the changes in the cerebral ventricular system in response to posterior vault distraction osteogenesis (PVDO) in patients with syndromic and nonsyndromic craniosynostosis. METHODS: A single-institution retrospective review of all patients with craniosynostosis undergoing PVDO from 2000 to 2022 was completed. Patients were included for analysis if they had pre and postoperative cranial computed tomography scans. Ventricular volume (VV) and intracranial volume (ICV) were calculated using segmentation software. RESULTS: Both patients with syndromic synostosis and nonsyndromic synostosis (NSS) experienced a significant increase in ICV after PVDO, but only patients with NSS experienced a significant VV change (P = 0.004). After normalization by ICV, total, lateral, and third VV changes retained significance with percentage increases of 114%, 117%, and 89%, respectively (P < 0.05 for all). CONCLUSION: The differing results between cohorts reinforce the concept that the intracranial milieu is different between patients with syndromic synostosis and NSS. The results of the NSS cohort suggest that these patients may exist in a compensated state in which a reduction in cerebral blood flow and VV allows for the maintenance of parenchymal health to prevent the development of intracranial hypertension. Further studies may explore VV as a surrogate marker of ICP elevation, and the utility of cranial vault remodeling on nonsynostotic pathologies with cephalocranial disproportion.

Biomodulatory Effects of Molecular Delivery in Human T Cells Using 3D-Printed Acoustofluidic Devices.

OBJECTIVE: Cell-based therapies have shown significant promise for treating many diseases, including cancer. Current cell therapy manufacturing processes primarily utilize viral transduction to insert genomic material into cells, which has limitations, including variable transduction efficiency and extended processing times. Non-viral transfection techniques are also limited by high variability or reduced molecular delivery efficiency. Novel 3D-printed acoustofluidic devices are in development to address these challenges by delivering biomolecules into cells within seconds via sonoporation. METHODS: In this study, we assessed biological parameters that influence the ultrasound-mediated delivery of fluorescent molecules (i.e., calcein and 150 kDa FITC-Dextran) to human T cells using flow cytometry and confocal imaging. RESULTS: Low cell plating densities (100,000 cells/mL) enhanced molecular delivery compared to higher cell plating densities (p < 0.001), even though cells were resuspended at equal concentrations for acoustofluidic processing. Additionally, cells in the S phase of the cell cycle had enhanced intracellular delivery compared to cells in the G2/M phase (p < 0.001) and G0/G1 phase (p < 0.01), while also maintaining higher viability compared to G0/G1 phase (p < 0.001). Furthermore, the calcium chelator (EGTA) decreased overall molecular delivery levels. Confocal imaging indicated that the actin cytoskeleton had important implications on plasma membrane recovery dynamics after sonoporation. In addition, confocal imaging indicates that acoustofluidic treatment can permeabilize the nuclear membrane, which could enable rapid intranuclear delivery of nucleic acids. CONCLUSIONS: The results of this study demonstrate that a 3D-printed acoustofluidic device can enhance molecular delivery to human T cells, which may enable improved techniques for non-viral processing of cell therapies.

Oxidatively-induced C(sp3)-C(sp3) bond formation at a tucked-in iron(iii) complex.

Carbon-carbon (C-C) bond formation is a cornerstone of synthetic chemistry, relying on routes such as transition-metal mediated cross-coupling for the introduction of new carbon-based functionality. For {[M] n+-C} (M = metal) structural units, studies that offer well-defined relationships between metal oxidation state, hydrocarbon strain, and {[M] n+-C} bond thermochemistry are thus informative, providing a means to reliably access new product classes. Here, we show that one-electron oxidation of the iron tucked-in complex [(η6-C5Me4[double bond, length as m-dash]CH2)Fe(dnppe)] (dnppe = 1,2-bis(di-n-propylphosphino)ethane) results in C(sp3)-C(sp3) bond formation giving unique {Fe2} dimers. Freeze-quenched CW X-band EPR spectroscopy allowed for spectroscopic identification of the reactive [(η6-C5Me4[double bond, length as m-dash]CH2)Fe(dnppe)]+ intermediate. Density functional theory (DFT) calculations reveal a primarily Fe-centered radical and a weak {[Fe]-C} bond (BDE[Fe]-C = 24.5 kcal mol-1, c.f. BDEC-C(ethane) = 90 kcal mol-1). For comparison, a structurally analogous Fe(iii) methyl complex was prepared, [Cp*Fe(dnppe)(CH3)]+ (Cp* = C5Me5 -), where C(sp3)-C(sp3) coupling was not observed, consistent with a larger calculated BDE[Fe]-C value of 47.8 kcal mol-1. These data are analogized to the simple hydrocarbons ethane and cyclopropane, where a strain-induced BDEC-C decrease of 33 kcal mol-1 is witnessed on cyclization.

Dropless Cataract Surgery: The Effect of Intracameral Phenylephrine/Ketorolac Infusion as a Single Agent on Postoperative Outcomes.

Objective The objective of this study was to assess the feasibility of using an intracameral phenylephrine/ketorolac infusion during cataract surgery as a single agent to prevent postoperative pain, inflammation, and other complications. Methods A prospective, single-group feasibility study was conducted in which phenylephrine/ketorolac infusion was administered during cataract surgery and no perioperative topical drops were initially prescribed. Patients underwent optical coherence tomography, corrected distance visual acuity testing, and slit lamp biomicroscopy examination at perioperative visits, during which they also reported symptoms of pain, irritation, and/or photophobia. A goal adverse event (AE) rate was set at ≤5.0%. Results A total of 94 eyes (60 patients) were included in this study. The AE rate was 13.8% (13/94 eyes) with pain/irritation in eight eyes, cystoid macular edema (CME) in three eyes, and corneal edema in three eyes. Conclusions Based on an AE rate goal of ≤5.0%, using intraoperative, intracameral phenylephrine/ketorolac alone was not deemed a feasible alternative to current postoperative eye drop regimens in our clinical setting. However, a 13.8% AE rate is comparable to the rates of postoperative CME, corneal edema, pain, and irritation in the published literature. Thus, more research is needed to truly define this approach as inferior or non-inferior to the current standard of care.

Unveiling a new oceanic anoxic event at the Norian/Rhaetian boundary (Late Triassic).

The latest Triassic was characterised by protracted biotic extinctions concluding in the End-Triassic Extinction (~ 200 Ma) and a global carbon cycle perturbation. The onset of declining diversity is closely related to reducing conditions that spread globally from upper Sevatian (uppermost Norian) to across the Norian-Rhaetian boundary, likely triggered by unusually high volcanic activity. We correlate significant organic carbon cycle perturbations to an increase of CO2 in the ocean-atmosphere system, likely outgassed by the Angayucham igneous province, the onset of which is indicated by the initiation of a rapid decline in 87Sr/86Sr and 188Os/187Os seawater values. A possible causal mechanism involves elevated CO2 levels causing global warming and accelerating chemical weathering, which increased nutrient discharge to the oceans and greatly increased biological productivity. Higher export production and oxidation of organic matter led to a global O2 decrease in marine water across the Norian/Rhaetian boundary (NRB). Biotic consequences of dysoxia/anoxia include worldwide extinctions in some fossil groups, such as bivalves, ammonoids, conodonts, radiolarians.

Universal pH electrocatalytic hydrogen evolution with Au-based high entropy alloys.

The creation of electrocatalysts with reduced concentrations of platinum-group metals remains a critical challenge for electrochemical hydrogen production. High-entropy alloys (HEAs) offer a distinct type of catalyst with tunable compositions and engineered surface activity, significantly enhancing the hydrogen evolution reaction (HER). We present the synthesis of AuPdFeNiCo HEA nanoparticles (NPs) using a wet impregnation method. The composition and structure of the AuPdFeNiCo HEA NPs are characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and high-resolution transmission electron microscopy (HR-TEM). These nanoparticles exhibit robust HER performance quantified over a broad pH range, with higher activity than any of the unary metal counterparts in all pHs. In comparison to a commercial 10%Pt/C electrocatalyst, AuPdFeNiCo HEA NPs exhibit enhanced electrochemical activity in both acidic and alkaline electrolytes at a current density of 10 mA cm-2. Additionally, these nanoparticles achieve a current density of 100 mA cm-2 at a voltage of 540 mV in neutral electrolytes, outperforming Pt/C which requires 570 mV. These findings help enable broad use of reduced precious metal electrocatalysts for water electrolysis in a variety of water and pH conditions.

Depressive symptoms and HIV among a cohort of adolescent young men and transgender women who have sex with men, Bangkok and Nakhon Sawan, Thailand, 2017-2019.

Screening for depression may identify persons for HIV prevention services and to ensure linkage to care for ART and mental health. We assessed factors associated with depressive symptoms using multiple logistic regression among 15- to 29-year-old gay, bisexual or other men who have sex with men (MSM) and transgender women who have sex with men (TGW) attending HIV prevention clinics at Silom Community Clinic or Bangrak Hospital in Bangkok or Rainbow Clinic in Nakhon Sawan, Thailand. We defined depressive symptoms as a self-report of feelings of sadness that impacted daily life in the past one month. Among 192 MSM, 51 TGW, and 11 gender-questioning persons screened: 12.6% met the criteria for depression; 5.9% had new HIV diagnosis. Independently associated factors which increase the risk of depressive symptoms included: studying in a private school (AOR 7.17); experiencing any type of bullying (AOR 2.8); having a partner with HIV (AOR 4.1); and learning about the study from sources other than a friend (AOR 4.2). Given many youths had depressive symptoms, screening for depression and connection to mental health services would be beneficial in sexual health settings to meet the needs of HIV-vulnerable youth.

A critical eye on metopic craniosynostosis: A retrospective study assessing orbital dysmorphology as a marker of disease.

This investigation sought to ascertain whether orbital morphology could predict genuine metopic craniosynostosis (MCS). The study retrospectively analyzed preoperative three-dimensional computed tomography (3D-CT) scans of patients who underwent surgical correction for MCS. MCS severity was evaluated using the interfrontal angle (IFA). Orbital dysmorphology was assessed based on multiple angles, including supraorbital notches and nasion (SNS), infraorbital foramina and nasion (INI), zygomaticofrontal suture-supraorbital notch-dacryon (ZSD), and orbital long axis (OLA). Results were juxtaposed against age/gender-matched controls and individuals with non-synostotic metopic ridge (MR). The study included 177 patients: 68 MCS, 35 MR, and 74 control subjects. All orbital measurements exhibited significant differences across groups. IFA demonstrated a strong association with all orbital measurements, particularly SNS (B = 0.79, p < 0.001). SNS showed the highest area under the curve among orbital measurements (0.89). Using a 95% sensitivity threshold, the optimal diagnostic angle for SNS was 129.23° (specificity 54%, sensitivity 96%). These findings suggest a correlation between orbital dysmorphology and trigonocephaly severity. The observed dysmorphology manifested in a superomedially accentuated rotational pattern. Importantly, SNS angle predicted MCS, with an angle greater than 130° indicating <5% likelihood of MCS diagnosis. The simplicity of measuring SNS angle on any 3D-CT scan highlights its practical use for assisting with MCS diagnosis.

Self-Assembled Origami Neural Probes for Scalable, Multifunctional, Three-Dimensional Neural Interface.

Flexible intracortical neural probes have drawn attention for their enhanced longevity in high-resolution neural recordings due to reduced tissue reaction. However, the conventional monolithic fabrication approach has met significant challenges in: (i) scaling the number of recording sites for electrophysiology; (ii) integrating of other physiological sensing and modulation; and (iii) configuring into three-dimensional (3D) shapes for multi-sided electrode arrays. We report an innovative self-assembly technology that allows for implementing flexible origami neural probes as an effective alternative to overcome these challenges. By using magnetic-field-assisted hybrid self-assembly, multiple probes with various modalities can be stacked on top of each other with precise alignment. Using this approach, we demonstrated a multifunctional device with scalable high-density recording sites, dopamine sensors and a temperature sensor integrated on a single flexible probe. Simultaneous large-scale, high-spatial-resolution electrophysiology was demonstrated along with local temperature sensing and dopamine concentration monitoring. A high-density 3D origami probe was assembled by wrapping planar probes around a thin fiber in a diameter of 80∼105 µm using optimal foldable design and capillary force. Directional optogenetic modulation could be achieved with illumination from the neuron-sized micro-LEDs (µLEDs) integrated on the surface of 3D origami probes. We could identify angular heterogeneous single-unit signals and neural connectivity 360° surrounding the probe. The probe longevity was validated by chronic recordings of 64-channel stacked probes in behaving mice for up to 140 days. With the modular, customizable assembly technologies presented, we demonstrated a novel and highly flexible solution to accommodate multifunctional integration, channel scaling, and 3D array configuration.

Characteristics of TPT initiation and completion among people living with HIV.

BACKGROUND: TB preventive treatment (TPT) reduces morbidity and mortality among people living with HIV (PLHIV). Despite the successful scale-up of TPT in Malawi, monitoring and evaluation have been suboptimal. We utilized the Malawi Population-Based HIV Impact Assessment (MPHIA) 2020-2021 survey data to estimate TPT uptake and completion among self-reported HIV-positive persons. METHODS: We estimated the proportion of HIV-positive respondents who had ever undergone TPT, and determined the percentage of those currently on TPT who had completed more than 6 months of treatment. Bivariate and multivariable logistic regression were performed to calculate the odds ratios for factors associated with ever-taking TPT. All variables were self-reported, and the analysis was weighted and accounted for in the survey design. RESULTS: Of the HIV+ respondents, 38.8% (95% CI 36.4-41.3) had ever taken TPT. The adjusted odds of ever taking TPT were 8.0 and 5.2 times as high in the Central and Southern regions, respectively, compared to the Northern region; 1.9 times higher among those in the highest wealth quintile, and 2.1 times higher for those on antiretroviral therapy >10 years. Of those currently taking TPT, 56.2% completed >6 months of TPT. CONCLUSION: These results suggest low TPT uptake and >6 months' completion rates among self-reported HIV+ persons. Initiatives to create demand and strengthen adherence would improve TPT uptake.

CONTEXTE: Le traitement préventif de la TB (TPT) réduit la morbidité et la mortalité chez les personnes vivant avec le VIH (PVVIH). Malgré l'extension réussie du TPT au Malawi, le suivi et l'évaluation n'ont pas été optimaux. Nous avons utilisé les données de l'enquête MPHIA (Malawi Population-Based HIV Impact Assessment) 2020­2021 pour estimer l'adoption et l'achèvement du TPT parmi les personnes se déclarant séropositives. MÉTHODES: Nous avons estimé la proportion de répondants séropositifs qui avaient déjà subi un TPT et déterminé le pourcentage de ceux qui sont actuellement sous TPT et qui ont terminé plus de 6 mois de traitement. Une régression logistique bivariée et multivariable a été effectuée pour calculer les rapports de cotes des facteurs associés au fait d'avoir déjà pris un TPT. Toutes les variables étaient autodéclarées et l'analyse a été pondérée et prise en compte dans la conception de l'enquête. RÉSULTATS: Parmi les répondants séropositifs, 38,8% (IC 95% 36,4­41,3) avaient déjà pris du TPT. Les probabilités ajustées de prise de TPT étaient 8,0 et 5,2 fois plus élevées dans les régions du centre et du sud, respectivement, que dans la région du nord ; 1,9 fois plus élevées chez les personnes appartenant au quintile de richesse le plus élevé, et 2,1 fois plus élevées chez les personnes suivant une thérapie antirétrovirale depuis plus de 10 ans. Parmi ceux qui prennent actuellement un TPT, 56,2% ont terminé >6 mois de TPT. CONCLUSION: Ces résultats suggèrent un faible taux d'utilisation du TPT et des taux d'achèvement de >6 mois parmi les personnes déclarées séropositives. Des initiatives visant à créer une demande et à renforcer l'adhésion permettraient d'améliorer l'utilisation du TPT.

Incomes to Outcomes: A Global Assessment of Disparities in Cleft and Craniofacial Treatment.

OBJECTIVE: Recent investigations focused on health equity have enumerated widespread disparities in cleft and craniofacial care. This review introduces a structured framework to aggregate findings and direct future research. DESIGN: Systematic review was performed to identify studies assessing health disparities based on race/ethnicity, payor type, income, geography, and education in cleft and craniofacial surgery in high-income countries (HICs) and low/middle-income countries (LMICs). Case reports and systematic reviews were excluded. Meta-analysis was conducted using fixed-effect models for disparities described in three or more studies. SETTING: N/A. PATIENTS: Patients with cleft lip/palate, craniosynostosis, craniofacial syndromes, and craniofacial trauma. INTERVENTIONS: N/A. RESULTS: One hundred forty-seven articles were included (80% cleft, 20% craniofacial; 48% HIC-based). Studies in HICs predominantly described disparities (77%,) and in LMICs focused on reducing disparities (42%). Level II-IV evidence replicated delays in cleft repair, alveolar bone grafting, and cranial vault remodeling for non-White and publicly insured patients in HICs (Grades A-B). Grade B-D evidence from LMICs suggested efficacy of community-based speech therapy and remote patient navigation programs. Meta-analysis demonstrated that Black patients underwent craniosynostosis surgery 2.8 months later than White patients (P < .001) and were less likely to undergo minimally-invasive surgery (OR 0.36, P = .002). CONCLUSIONS: Delays in cleft and craniofacial surgical treatment are consistently identified with high-level evidence among non-White and publicly-insured families in HICs. Multiple tactics to facilitate patient access and adapt multi-disciplinary case in austere settings are reported from LMICs. Future efforts including those sharing tactics among HICs and LMICs hold promise to help mitigate barriers to care.

Balancing selection and the functional effects of shared polymorphism in cryptic Daphnia species.

The patterns of genetic variation within and between related taxa represent the genetic history of a species. Shared polymorphisms, loci with identical alleles across species, are of unique interest as they may represent cases of ancient selection maintaining functional variation post-speciation. In this study, we investigate the abundance of shared polymorphism in the Daphnia pulex species complex. We test whether shared mutations are consistent with the action of balancing selection or alternative hypotheses such as hybridization, incomplete lineage sorting, or convergent evolution. We analyzed over 2,000 genomes from North American and European D. pulex and several outgroup species to examine the prevalence and distribution of shared alleles between the focal species pair, North American and European D. pulex. We show that while North American and European D. pulex diverged over ten million years ago, they retained tens of thousands of shared alleles. We found that the number of shared polymorphisms between North American and European D. pulex cannot be explained by hybridization or incomplete lineage sorting alone. Instead, we show that most shared polymorphisms could be the product of convergent evolution, that a limited number appear to be old trans-specific polymorphisms, and that balancing selection is affecting young and ancient mutations alike. Finally, we provide evidence that a blue wavelength opsin gene with trans-specific polymorphisms has functional effects on behavior and fitness in the wild. Ultimately, our findings provide insights into the genetic basis of adaptation and the maintenance of genetic diversity between species.

Orthognathic Considerations of Maxillary and Mandibular Asymmetry at Skeletal Maturity in Patients with Cleft Lip and Palate.

BACKGROUND: Improving occlusion and aesthetics is the primary objective of orthognathic surgery for patients with cleft lip and palate (CLP). However, these patients often suffer from horizontal, vertical, and rotational asymmetry in addition to maxillary retrusion. This study aims to describe maxillary and mandibular asymmetry in patients with CLP undergoing orthognathic surgery and analyze its anatomic basis. METHODS: Patients with isolated CLP undergoing CT imaging prior to orthognathic surgery were retrospectively reviewed. Maxillary and mandibular positioning and dimensional symmetry were evaluated. Incidence of clinically significant asymmetry, correlations between areas of asymmetry, and associations with clinical history were analyzed. RESULTS: Fifty-eight patients, with mean age 17 years were analyzed, including 32 patients with unilateral CLP and 26 with bilateral CLP. Twenty (34%) patients demonstrated chin deviation ≥4mm and 21 (36%) had a ≥5% discrepancy in mandibular ramus lengths. Horizontal occlusal plane cant of ≥2° was seen in 20 (34%) maxillae and 28 (48%) mandibles, with dental arch yaw ≥2° noted in 32 (55%) of both maxillae and mandibles. Chin deviation correlated with maxillary cant, discrepancy in ramus length, discrepancy in mandibular body length, and discrepancy in condylar volume (p<0.05). Bilateral and unilateral CLP did not show significantly different asymmetry on any measure (p>0.05). CONCLUSIONS: Both maxillary and mandibular asymmetry is common in skeletally mature patients with CLP and frequently results in notable chin deviation. Preoperative three-dimensional imaging and virtual surgical planning of orthognathic surgery aid in recognition of facial asymmetries and reveal opportunities to optimize results in this population.

2D Time-Domain Spectroscopy for Determination of Energy and Momentum Relaxation Rates of Hydrogen-Like Donor States in Germanium.

We present measurements of the coherence times of excited states of hydrogen-like arsenic impurities in germanium (Ge:As) using a table-top two-dimensional time-domain spectroscopy (2D-TDS) system. We show that this laboratory system is capable of resolving the coherence lifetimes of atomic-like excited levels of impurity centers in semiconductors, such as those used in solid-state quantum information technologies, on a subpicosecond time scale. By fitting the coherent nonlinear response of the system with the known intracenter transition frequencies, we are able to monitor coherent population transfer and decay of the transitions from the 2p0 and 2p± states for different low excitation pulse fields. Furthermore, by examining the off-diagonal resonances in the 2D frequency-domain map, we are able to identify coherences between excited electronic states that are not visible via conventional single-frequency pump-probe or Hahn-echo measurements.

Inhibition of Acyl-CoA Synthetase Long Chain Isozymes Decreases Multiple Myeloma Cell Proliferation and Causes Mitochondrial Dysfunction.

Multiple myeloma (MM) is an incurable cancer of plasma cells with a 5-year survival rate of 59%. Dysregulation of fatty acid (FA) metabolism is associated with MM development and progression; however, the underlying mechanisms remain unclear. Acyl-CoA synthetase long-chain family members (ACSLs) convert free long-chain fatty acids into fatty acyl-CoA esters and play key roles in catabolic and anabolic fatty acid metabolism. The Cancer Dependency Map data suggested that ACSL3 and ACSL4 were among the top 25% Hallmark Fatty Acid Metabolism genes that support MM fitness. Here, we show that inhibition of ACSLs in human myeloma cell lines using the pharmacological inhibitor Triascin C (TriC) causes apoptosis and decreases proliferation in a dose- and time-dependent manner. RNA-seq of MM.1S cells treated with TriC for 24 h showed a significant enrichment in apoptosis, ferroptosis, and ER stress. Proteomics of MM.1S cells treated with TriC for 48 h revealed that mitochondrial dysfunction and oxidative phosphorylation were significantly enriched pathways of interest, consistent with our observations of decreased mitochondrial membrane potential and increased mitochondrial superoxide levels. Interestingly, MM.1S cells treated with TriC for 24 h also showed decreased mitochondrial ATP production rates and overall lower cellular respiration.

Sociodemographic Factors Predict Long-Term Attrition from Multidisciplinary Cleft Clinic.

OBJECTIVE: Identify and describe factors associated with retention and attrition of patients during longitudinal follow-up at multidisciplinary cleft clinic. DESIGN: Retrospective cohort study. SETTING: Single, tertiary care center. PATIENTS, PARTICIPANTS: Patients born between 1995 and 2007 with a diagnosis of cleft palate with or without cleft lip attending multidisciplinary cleft clinic. INTERVENTIONS: None tested, observational study. MAIN OUTCOME MEASURE(S): Age at last clinical appointment with a multidisciplinary cleft team provider. Attrition was defined as absence of an outpatient appointment following 15 years of age. RESULTS: Six hundred seventy-eight patients were included. The average age at last appointment across the entire cohort was 13.1 years (IQR 6.6-17.2). Patients who were Black (HR 1.60, 95% CI 1.10-2.32, p = 0.014) and other races (HR 1.90, 95% CI 1.22-2.98, p = 0.004) were more likely to be lost to follow-up compared to white patients. Publicly insured patients were more likely to experience attrition than those who were privately insured (HR 1.30, 95% CI 1.03-1.65, p = 0.030). Estimated income was not significantly associated with length of follow-up (p = 0.259). Those whose residence was in the fourth quartile of driving distance from our center experienced loss to follow-up significantly more than those who lived the closest (HR 2.04, 95% CI 1.50-2.78, p < 0.001). CONCLUSIONS: There is a high degree of follow-up attrition among patients with cleft lip and palate. Race, insurance status, and driving distance to our center were associated with attrition in a large, retrospective cohort of patients who have reached the age of cleft clinic graduation.