Triad of hypovitaminosis A, hyperostosis, and optic neuropathy in males with autism spectrum disorders.

BACKGROUND: Persons with autism spectrum disorder (ASD) can have restrictive diets due to stereotyped behaviors. These restrictive diets can manifest with nutritional deficiencies, such as Vitamin A deficiency. The most frequent manifestation of hypovitaminosis A is vision loss secondary to xerophthalmia. Here the authors report six cases of males with a clinical triad of hypovitaminosis A, cranial hyperostosis, and optic neuropathy. METHODS: A retrospective case series of six males (ages 5-17 years old) with ASD who presented with several weeks of vision loss and nyctalopia were reviewed. RESULTS: All six subjects were found to have a barely detectable Vitamin A level (<10 mcg/dL). Three of the six cases had elevated protein (45.9-74.0 mg/dL) in their CSF. MRI imaging demonstrated mild T2 enhancement of bilateral optic nerve sheaths and CT showed diffuse skull hypertrophy. Upon further history collection, all subjects had a very limited food repertoire with major nutritional deficiencies. Subjects were prescribed high doses of vitamin A and most were noted to have improved vision at follow-up, and all had resolution of imaging abnormalities on repeat scans. No common genetic variant was identified in patients with expanded genetic sequencing. CONCLUSIONS: We present a clinical triad of hypovitaminosis A, cranial hyperostosis, and optic neuropathy in six males with ASD. Skull abnormalities and xeropthalmia likely contributed to the development of vision loss.

Predictors of faculty narrative evaluation quality in medical school clerkships.

INTRODUCTION: Narrative approaches to assessment provide meaningful and valid representations of trainee performance. Yet, narratives are frequently perceived as vague, nonspecific and low quality. To date, there is little research examining factors associated with narrative evaluation quality, particularly in undergraduate medical education. The purpose of this study was to examine associations of faculty- and student-level characteristics with the quality of faculty member's narrative evaluations of clerkship students. METHODS: The authors reviewed faculty narrative evaluations of 50 students' clinical performance in their inpatient medicine and neurology clerkships, resulting in 165 and 87 unique evaluations in the respective clerkships. The authors evaluated narrative quality using the Narrative Evaluation Quality Instrument (NEQI). The authors used linear mixed effects modelling to predict total NEQI score. Explanatory covariates included the following: time to evaluation completion, number of weeks spent with student, faculty total weeks on service per year, total faculty years in clinical education, student gender, faculty gender, and an interaction term between student and faculty gender. RESULTS: Significantly higher narrative evaluation quality was associated with a shorter time to evaluation completion, with NEQI scores decreasing by approximately 0.3 points every 10 days following students' rotations (p = .004). Additionally, women faculty had statistically higher quality narrative evaluations with NEQI scores 1.92 points greater than men faculty (p = .012). All other covariates were not significant. CONCLUSIONS: The quality of faculty members' narrative evaluations of medical students was associated with time to evaluation completion and faculty gender but not faculty experience in clinical education, faculty weeks on service, or the amount of time spent with students. Findings advance understanding on ways to improve the quality of narrative evaluations which are imperative given assessment models that will increase the volume and reliance on narratives.

Consensus recommendations for the classification and long-term follow up of infants who screen positive for Krabbe Disease.

OBJECTIVE: To provide updated evidence and consensus-based recommendations for the classification of individuals who screen positive for Krabbe Disease (KD) and recommendations for long-term follow-up for those who are at risk for late onset Krabbe Disease (LOKD). METHODS: KD experts (KD NBS Council) met between July 2017 and June 2020 to develop consensus-based classification and follow-up recommendations. The resulting newly proposed recommendations were assessed in a historical cohort of 47 newborns from New York State who were originally classified at moderate or high risk for LOKD. RESULTS: Infants identified by newborn screening with possible KD should enter one of three clinical follow-up pathways (Early infantile KD, at-risk for LOKD, or unaffected), based on galactocerebrosidase (GALC) activity, psychosine concentration, and GALC genotype. Patients considered at-risk for LOKD based on low GALC activity and an intermediate psychosine concentration are further split into a high-risk or low-risk follow-up pathway based on genotype. Review of the historical New York State cohort found that the updated follow-up recommendations would reduce follow up testing by 88%. CONCLUSION: The KD NBS Council has presented updated consensus recommendations for efficient and effective classification and follow-up of NBS positive patients with a focus on long-term follow-up of those at-risk for LOKD.

Evolution and biogeography of Memecylon.

PREMISE: The woody plant group Memecylon (Melastomataceae) is a large clade occupying diverse forest habitats in the Old World tropics and exhibiting high regional endemism. Its phylogenetic relationships have been previously studied using ribosomal DNA with extensive sampling from Africa and Madagascar. However, divergence times, biogeography, and character evolution of Memecylon remain uninvestigated. We present a phylogenomic analysis of Memecylon to provide a broad evolutionary perspective of this clade. METHODS: One hundred supercontigs of 67 Memecylon taxa were harvested from target enrichment. The data were subjected to coalescent and concatenated phylogenetic analyses. A timeline was provided for Memecylon evolution using fossils and secondary calibration. The calibrated Memecylon phylogeny was used to elucidate its biogeography and ancestral character states. RESULTS: Relationships recovered by the phylogenomic analyses are strongly supported in both maximum likelihood and coalescent-based species trees. Memecylon is inferred to have originated in Africa in the Eocene and subsequently dispersed predominantly eastward via long-distance dispersal (LDD), although a reverse dispersal from South Asia westward to the Seychelles was postulated. Morphological data exhibited high levels of homoplasy, but also showed that several vegetative and reproductive characters were phylogenetically informative. CONCLUSIONS: The current distribution of Memecylon appears to be the result of multiple ancestral LDD events. Our results demonstrate the importance of the combined effect of geographic and paleoclimatic factors in shaping the distribution of this group in the Old World tropics. Memecylon includes a number of evolutionarily derived morphological features that contribute to diversity within the clade.

Computationally Assisted Discovery and Assignment of a Highly Strained and PANC-1 Selective Alkaloid from Alaska's Deep Ocean.

We report here the orchestration of molecular ion networking and a set of computationally assisted structural elucidation approaches in the discovery of a new class of pyrroloiminoquinone alkaloids that possess selective bioactivity against pancreatic cancer cell lines. Aleutianamine represents the first in a new class of pyrroloiminoquinone alkaloids possessing a highly strained multibridged ring system, discovered from Latrunculia ( Latrunculia) austini Samaai, Kelly & Gibbons, 2006 (class Demospongiae, order Poecilosclerida, family Latrunculiidae) recovered during a NOAA deep-water exploration of the Aleutian Islands. The molecule was identified with the guidance of mass spectrometry, nuclear magnetic resonance, and molecular ion networking (MoIN) analysis. The structure of aleutianamine was determined using extensive spectroscopic analysis in conjunction with computationally assisted quantifiable structure elucidation tools. Aleutianamine exhibited potent and selective cytotoxicity toward solid tumor cell lines including pancreatic cancer (PANC-1) with an IC50 of 25 nM and colon cancer (HCT-116) with an IC50 of 1 µM, and represents a potent and selective candidate for advanced preclinical studies.

Strained-layer-superlattice-based compact thermal imager for the International Space Station.

The compact thermal imager (CTI) is a dual-band, strained-layer-superlattice (SLS) detector-based instrument that was installed on the exterior of the International Space Station (ISS) in conjunction with the third Robotic Refueling Mission 3 (RRM3) in 2018. The CTI serves as a pathfinder for future thermal infrared capability on Landsat. The CTI incorporates an SLS hybrid, a dual-band 3-5 and 8-10 µm, electrically switchable, 320×256 array with 30 µm2 pixels, bonded to an Indigo ISC0903 Readout Integrated Circuit (ROIC). The telescope was built around an integrated detector cryocooler assembly developed under a NASA Small Business Innovative Research award with QmagiQ, LLC. The cooler is a Ricor K508 and the front-end optics is a custom-designed, doublet lens telescope with a 150 mm focal length. The ground resolution is 80 meters/pixel from the ISS altitude of 400 km. A filter creates two spectral channels from the dual bands, 3.3-5.4 and 7.8-10.2 µm. The detector hybrid control electronics is a custom-developed system based on the Teledyne Imaging Systems SIDECAR Application-Specific Integrated Circuit. This module provides the electronic interface from the RRM3 SpaceCube on-board processor to the detector/ROIC assembly. The primary goal of this mission was to perform a technology demonstration of the SLS technology and the commercial cooler technology elevating the Technology Readiness Level (TRL) to TRL 9 on a bare-bones budget and relatively fast development cycle. Some science objectives include locating fires, approximating land surface temperatures, and monitoring evapotranspiration, sea ice, and glacier dynamics. In this paper, we will present the design of the focal plane, optics, electronics, and mechanical structure of the CTI. We will also describe the operation and qualification tests that were performed to bring the CTI to the NASA TRL 6 in preparation for the launch on a SpaceX Dragon from the Kennedy Space Center.

Biallelic mutations in the homeodomain of NKX6-2 underlie a severe hypomyelinating leukodystrophy.

Hypomyelinating leukodystrophies are genetically heterogeneous disorders with overlapping clinical and neuroimaging features reflecting variable abnormalities in myelin formation. We report on the identification of biallelic inactivating mutations in NKX6-2, a gene encoding a transcription factor regulating multiple developmental processes with a main role in oligodendrocyte differentiation and regulation of myelin-specific gene expression, as the cause underlying a previously unrecognized severe variant of hypomyelinating leukodystrophy. Five affected subjects (three unrelated families) were documented to share biallelic inactivating mutations affecting the NKX6-2 homeobox domain. A trio-based whole exome sequencing analysis in the first family detected a homozygous frameshift change [c.606delinsTA; p.(Lys202Asnfs*?)]. In the second family, homozygosity mapping coupled to whole exome sequencing identified a homozygous nucleotide substitution (c.565G>T) introducing a premature stop codon (p.Glu189*). In the third family, whole exome sequencing established compound heterozygosity for a non-conservative missense change affecting a key residue participating in DNA binding (c.599G>A; p.Arg200Gln) and a nonsense substitution (c.589C>T; p.Gln197*), in both affected siblings. The clinical presentation was homogeneous, with four subjects having severe motor delays, nystagmus and absent head control, and one individual showing gross motor delay at the age of 6 months. All exhibited neuroimaging that was consistent with hypomyelination. These findings define a novel, severe form of leukodystrophy caused by impaired NKX6-2 function.

Sesterterpenoid and Steroid Metabolites from a Deep-Water Alaska Sponge Inhibit Wnt/ß-Catenin Signaling in Colon Cancer Cells.

The Wnt/ß-catenin signaling pathway is known to play critical roles in a wide range of cellular processes: cell proliferation, differentiation, migration and embryonic development. Importantly, dysregulation of this pathway is tightly associated with pathogenesis in most human cancers. Therefore, the Wnt/ß-catenin pathway has emerged as a promising target in anticancer drug screening programs. In the present study, we have isolated three previously unreported metabolites from an undescribed sponge, a species of Monanchora (Order Poecilosclerida, Family Crambidae), closely related to the northeastern Pacific species Monanchora pulchra, collected from deep waters off the Aleutian Islands of Alaska. Through an assortment of NMR, MS, ECD, computational chemical shifts calculation, and DP4, chemical structures of these metabolites have been characterized as spirocyclic ring-containing sesterterpenoid (1) and cholestane-type steroidal analogues (2 and 3). These compounds exhibited the inhibition of ß-catenin response transcription (CRT) through the promotion of ß-catenin degradation, which was in part implicated in the antiproliferative activity against two CRT-positive colon cancer cell lines.

The Soothing Sea: A Virtual Coastal Walk Can Reduce Experienced and Recollected Pain.

Virtual reality (VR) distraction has become increasingly available in health care contexts and is used in acute pain management. However, there has been no systematic exploration of the importance of the content of VR environments. Two studies tested how interacting with nature VR influenced experienced and recollected pain after 1 week. Study 1 (n = 85) used a laboratory pain task (cold pressor), whereas Study 2 (n = 70) was a randomized controlled trial with patients undergoing dental treatment. In Study 1, nature (coastal) VR reduced both experienced and recollected pain compared with no VR. In Study 2, nature (coastal) VR reduced experienced and recalled pain in dental patients, compared with urban VR and standard care. Together, these data show that nature can improve experience of health care procedures through the use of VR, and that the content of the VR matters: Coastal nature is better than urban.

Numerical versus narrative: A comparison between methods to measure medical student performance during clinical clerkships.

BACKGROUND: Medical school evaluations typically rely on both language-based narrative descriptions and psychometrically converted numeric scores to convey performance to the grading committee. We evaluated inter-rater reliability and correlation of numeric versus narrative evaluations for students on their Neurology Clerkship. DESIGN/METHODS: 50 Neurology Clerkship in-training evaluation reports completed by their residents and faculty members at the University of Rochester School of Medicine were dissected into narrative and numeric components. 5 Clerkship grading committee members retrospectively gave new narrative scores (NNS) while blinded to original numeric scores (ONS). We calculated intra-class correlation coefficients (ICC) and their associated confidence intervals for the ONS and the NNS. In addition, we calculated the correlation between ONS and NNS. RESULTS: The ICC was greater for the NNS (ICC = .88 (95% CI = .70-.94)) than the ONS (ICC = .62 (95% CI = .40-.77)) Pearson correlation coefficient showed that the ONS and NNS were highly correlated (r = .81). CONCLUSIONS: Narrative evaluations converted by a small group of experienced graders are at least as reliable as numeric scoring by individual evaluators. We could allow evaluators to focus their efforts on creating richer narrative of greater value to trainees.

A 'mixed reality' simulator concept for future Medical Emergency Response Team training.

The UK Defence Medical Service's Pre-Hospital Emergency Care (PHEC) capability includes rapid-deployment Medical Emergency Response Teams (MERTs) comprising tri-service trauma consultants, paramedics and specialised nurses, all of whom are qualified to administer emergency care under extreme conditions to improve the survival prospects of combat casualties. The pre-deployment training of MERT personnel is designed to foster individual knowledge, skills and abilities in PHEC and in small team performance and cohesion in 'mission-specific' contexts. Until now, the provision of airborne pre-deployment MERT training had been dependent on either the availability of an operational aircraft (eg, the CH-47 Chinook helicopter) or access to one of only two ground-based facsimiles of the Chinook's rear cargo/passenger cabin. Although MERT training has high priority, there will always be competition with other military taskings for access to helicopter assets (and for other platforms in other branches of the Armed Forces). This paper describes the development of an inexpensive, reconfigurable and transportable MERT training concept based on 'mixed reality' technologies-in effect the 'blending' of real-world objects of training relevance with virtual reality reconstructions of operational contexts.

Drill-Assisted Biopsy of the Axial and Appendicular Skeleton: Safety, Technical Success, and Diagnostic Efficacy.

The purpose of this study was to evaluate the safety, technical success rate, and diagnostic efficacy of drill-assisted axial and appendicular bone biopsies. During a 3-y period, 703 drill-assisted biopsies were performed. The cohort included 54.2% men, with a mean age of 57.6 y ± 17.1. Median lesion volume was 10.9 mL (interquartile range, 3.4-30.2 mL). Lesions were lytic (31.7%), sclerotic (21.2%), mixed lytic and sclerotic (27.7%), or normal radiographic bone quality (19.3%). No complications were reported. The technical biopsy success rate was 99.9%. Crush artifact was present in 5.8% of specimens submitted for surgical pathologic examination, and 2.1% of specimens were inadequate for histologic evaluation.

The diagnostic workup of children with the radiologically isolated syndrome differs by age and by sex.

BACKGROUND: Cerebrospinal fluid (CSF) and spinal MRIs are often obtained in children with the radiologically isolated syndrome (RIS) for diagnosis and prognosis. Factors affecting the frequency and timing of these tests are unknown. OBJECTIVE: To determine whether age or sex were associated with (1) having CSF or spinal MRI obtained or (2) the timing of these tests. METHODS: We analyzed children (≤ 18 y) with RIS enrolled in an international longitudinal study. Index scans met 2010/2017 multiple sclerosis (MS) MRI criteria for dissemination in space (DIS). We used Fisher's exact test and multivariable logistic regression (covariates = age, sex, MRI date, MRI indication, 2005 MRI DIS criteria met, and race). RESULTS: We included 103 children with RIS (67% girls, median age = 14.9 y). Children ≥ 12 y were more likely than children < 12 y to have CSF obtained (58% vs. 21%, adjusted odds ratio [AOR] = 4.9, p = 0.03). Pre-2017, girls were more likely than boys to have CSF obtained (n = 70, 79% vs. 52%, AOR = 4.6, p = 0.01), but not more recently (n = 30, 75% vs. 80%, AOR = 0.2, p = 0.1; p = 0.004 for interaction). Spinal MRIs were obtained sooner in children ≥ 12 y (median 11d vs. 159d, p = 0.03). CONCLUSIONS: Younger children with RIS may be at continued risk for misdiagnosis and misclassification of MS risk. Consensus guidelines are needed.

Integrated tunable CMOS laser.

An integrated tunable CMOS laser for silicon photonics, operating at the C-band, and fabricated in a commercial CMOS foundry is presented. The III-V gain medium section is embedded in the silicon chip, and is hermetically sealed. The gain section is metal bonded to the silicon substrate creating low thermal resistance into the substrate and avoiding lattice mismatch problems. Optical characterization shows high performance in terms of side mode suppression ratio, relative intensity noise, and linewidth that is narrow enough for coherent communications.

Effect of varying the concentrations of carbohydrate and milk protein in rehydration solutions ingested after exercise in the heat.

The present study investigated the relationship between the milk protein content of a rehydration solution and fluid balance after exercise-induced dehydration. On three occasions, eight healthy males were dehydrated to an identical degree of body mass loss (BML, approximately 1·8%) by intermittent cycling in the heat, rehydrating with 150% of their BML over 1 h with either a 60 g/l carbohydrate solution (C), a 40 g/l carbohydrate, 20 g/l milk protein solution (CP20) or a 20 g/l carbohydrate, 40 g/l milk protein solution (CP40). Urine samples were collected pre-exercise, post-exercise, post-rehydration and for a further 4 h. Subjects produced less urine after ingesting the CP20 or CP40 drink compared with the C drink (P<0·01), and at the end of the study, more of the CP20 (59 (SD 12)%) and CP40 (64 (SD 6)%) drinks had been retained compared with the C drink (46 (SD 9)%) (P<0·01). At the end of the study, whole-body net fluid balance was more negative for trial C (- 470 (SD 154) ml) compared with both trials CP20 (- 181 (SD 280) ml) and CP40 (2107 (SD 126) ml) (P<0·01). At 2 and 3 h after drink ingestion, urine osmolality was greater for trials CP20 and CP40 compared with trial C (P<0·05). The present study further demonstrates that after exercise-induced dehydration, a carbohydrate--milk protein solution is better retained than a carbohydrate solution. The results also suggest that high concentrations of milk protein are not more beneficial in terms of fluid retention than low concentrations of milk protein following exercise-induced dehydration.

New glass sponges (Porifera: Hexactinellida) from deep waters of the central Aleutian Islands, Alaska.

Hexactinellida from deep-water communities of the central Aleutian Islands, Alaska, are described. They were mostly collected by the remotely operated vehicle 'Jason II' from 494­2311 m depths during a 2004 RV 'Roger Revelle' expedition, but one shallow-water species collected with a shrimp trawl from 155 m in the same area is included. The excellent condition of the ROV-collected specimens enabled valuable redescription of some species previously known only from badly damaged specimens. New taxa include one new genus and eight new species in five families. Farreidae consist of two new species, Farrea aleutiana and F. aspondyla. Euretidae consists of only Pinulasma fistulosum n. gen., n. sp. Tretodictyidae include only Tretodictyum amchitkensis n. sp. Euplectellidae consists of only the widespread species Regadrella okinoseana Ijima, reported here over 3,700 km from its closest previously known occurrence. The most diverse family, Rossellidae, consists of Aulosaccus ijimai (Schulze), Aulosaccus schulzei Ijima, Bathydorus sp. (young stage not determinable to species), Caulophacus (Caulophacus) adakensis n. sp., Acanthascus koltuni n. sp., Staurocalyptus psilosus n. sp., Staurocalyptus tylotus n. sp. and Rhabdocalyptus mirabilis Schulze. We present argument for reinstatement of the abolished rossellid subfamily Acanthascinae and return of the subgenera 　Staurocalyptus Ijima and Rhabdocalyptus Schulze to their previous generic status. These fauna provides important complexity to the hard substrate communities that likely serve as nursery areas for the young stages of commercially important fish and crab species, refuge from predation for both young and adult stages, and also as a focal source of prey for juvenile and adult stages of those same species.

Four new species of Haplosclerida (Porifera, Demospongiae) from the Aleutian Islands, Alaska.

Four new species of Haplosclerida are described from the Aleutian Islands, Alaska: Callyspongia mucosa n.sp., Cladocroce infundibulum n. sp., Cladocroce attu n. sp. and Cladocroce kiska n. sp. The new species are described and compared to congeners of the region. This is the northernmost record of the genus Callyspongia and the first record of the subgenus Callyspongia from the North Pacific Ocean. To accommodate Cladocroce kiska in its genus the definition has to be broadened to allow sigmas.

Treatment planning for patients with tooth wear.

Providing restorative dental care for patients with tooth wear can, at times, seem complex and demanding. The key to this process lies in a systematic approach that breaks down the component parts. In this chapter, the importance of a comprehensive assessment at the outset will be highlighted. This should include identification of the patient's chief complaint, taking a thorough history, completing the clinical examination, undertaking any special tests and arriving at clinical diagnoses. Together, this information will influence the treatment planning process, identify appropriate treatment concepts and options available and the individual stages that may be involved. The process should be both holistic and thorough to enable the patient and clinician to build a clear pathway and vision. In parallel, and with patient input throughout, it is essential to manage patient expectations as best as possible whilst remaining pragmatic and honest about treatment outcomes, longevity of restorations and the risks of failure.

The Wise Adviser Trap: Catastrophic Decision-Making in Herodotus and Thucydides.

This paper reads parallel scenes in Herodotus and Thucydides to find a shared emphasis on flawed deliberation as the cause of catastrophic defeats for imperial powers. Both texts question the foresight and rhetorical strategies of self-styled wise advisers who ironically advance the very decisions they seek to forestall. Yet both authors also suggest that better strategies of advice could have altered the outcome. In contrast with those who read Herodotus and Thucydides as fatalists showing the futility of wise counsel in the face of imperial aggression, we find that they evince a belief in the constructive possibilities of advice.

Managing total knee replacement under value-based payments.

OBJECTIVES: To evaluate opportunity gaps and set outcome goals in knee replacement (KR) between a primary care group taking financial risk for managing its patients and 6 fee-for-service (FFS) orthopedic groups that serve their patients. STUDY DESIGN: The opportunity gap analysis was a cross-sectional evaluation of the outcomes of interest on a risk-adjusted basis using orthopedic groups, the primary care group's patients, and regional comparisons. The impact evaluation was a historical cohort comparison tracking outcomes of interest over the time frame of the intervention. METHODS: Using risk-adjusted Medicare data, we defined opportunity gaps in the following outcomes: density of KR surgery, site of KR surgery, postacute care placement, and complications. RESULTS: Opportunity gap analysis demonstrated the following variation on a regional basis: a 2-fold difference in density of KR, a 3-fold difference in outpatient surgery, and a 2.5-fold difference in institutional postacute care placement. In the impact evaluation comparing 2019 with 2021, the primary care group's patients had reduced density of KR surgeries from 15.5 per 1000 to 13.0 per 1000, an increase in outpatient surgery from 31.0% to 81.6%, and a reduction in institutional postacute care utilization from 16.0% to 6.1%. Less pronounced trends were seen in the region for all Medicare FFS patients. These results were achieved with stable complication rates, which had an observed/expected ratio of 0.61 in 2019 and 0.63 in 2021. CONCLUSIONS: We achieved alignment of incentives through use of performance information with specific goals and promise of referrals to value-based partners. This approach resulted in improved value to patients with no evidence of harm and is translatable to other specialty care and markets.