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For diversity to exist in the medical graduate workforce, students from all backgrounds should have equitable opportunities of employment. Specialties have utilized a minimal threshold for USMLE Step 1 score when screening applicants for residency interviews. The OHSU SOM class of 2021 completed a 14-question voluntary survey on their Step 1 score and the following non-modifiable risk factors: Adverse Childhood Experience score (ACEs), sex, gender, Underrepresented in Medicine status (URiM), family income during adolescence, highest degree held by a guardian, discrimination experience during medical school, federal/state assistance use, and rural versus urban primary home. Descriptive statistics and unadjusted risk ratios were applied to study the relation between Step 1 score and non-modifiable risk factors as well as certain non-modifiable risk factors and ACEs ≥ 3. The mean Step 1 score was 230 (213, 247). Of the students, 28.2% identified ACEs ≥ 3, 13.6% were considered URiM, and 65.4% were female. URiM were 2.34 (1.30, 4.23),females were 2.77 (1.06-7.29), and those who experienced discrimination in medical school were 4.25 (1.85, 9.77) times more likely to have ACEs ≥ 3. Students who had ACEs ≥ 3 were 3.58 (1.75, 7.29) times less likely to meet a minimal threshold for residency interviews of 220. These are the first results to demonstrate a relationship between Step 1 score and ACEs. Those who identified as URiM, females, and those who experienced discrimination in medical school were at a higher risk of ACEs of ≥ 3. Step 1 transitioned to pass/fail in January 2022. However, the first application cycle that residencies will see pass/fail scoring is 2023-2024, and fellowships will continue to see scored Step 1 until, at the earliest, the 2026-2027 application cycle. These data contribute to a foundation of research that could apply to Step 2CK testing scores, and help to inform decisions about the diversity and equity of the residency interview process.

Network connectivity is an integral feature of human brain function, and characterising its maturational trajectory is a critical step towards understanding healthy and atypical neurodevelopment. Here, we used magnetoencephalography (MEG) to investigate both stationary (i.e. time averaged) and rapidly modulating (dynamic) electrophysiological connectivity, in participants aged from mid-childhood to early adulthood (youngest participant 9 years old; oldest participant 25 years old). Stationary functional connectivity (measured via inter-regional coordination of neural oscillations) increased with age in the alpha and beta frequency bands, particularly in bilateral parietal and temporo-parietal connections. Our dynamic analysis (also applied to alpha/beta oscillations) revealed the spatiotemporal signatures of 8 dynamic networks; these modulate on a ∼100 ms time scale, and temporal stability in attentional networks was found to increase with age. Significant overlap was found between age-modulated dynamic networks and inter-regional oscillatory coordination, implying that altered network dynamics underlie age related changes in functional connectivity. Our results provide novel insights into brain network electrophysiology, and lay a foundation for future work in childhood disorders. •We studied static and dynamic connectivity change between mid-childhood and adulthood.•Static (time averaged) connectivity increases with age in alpha and beta bands.•Connectivity changes with age are strongest in attentional networks.•Temporal stability in attentional networks was found to increase with age.•Changing network dynamics underlies changes in time averaged functional connectivity.

Children treated for brain tumors often experience social and emotional difficulties, including challenges with emotion regulation; our goal was to investigate the attention-related component processes of emotion regulation, using a novel eye-tracking measure, and to evaluate its relations with emotional functioning and white matter (WM) organization. Fifty-four children participated in this study; 36 children treated for posterior fossa tumors, and 18 typically developing children. Participants completed two versions of an emotion regulation eye-tracking task, designed to differentiate between implicit (i.e., automatic) and explicit (i.e., voluntary) subprocesses. The Emotional Control scale from the Behavior Rating Inventory of Executive Function was used to evaluate emotional control in daily life, and WM organization was assessed with diffusion tensor imaging. We found that emotional faces captured attention across all groups (F(1,51) = 32.18, p < .001, η2p = .39). However, unlike typically developing children, patients were unable to override the attentional capture of emotional faces when instructed to (emotional face-by-group interaction: F(2,51) = 5.58, p = .006, η2p = .18). Across all children, our eye-tracking measure of emotion regulation was modestly associated with the parent-report emotional control score (r = .29, p = .045), and in patients it was associated with WM microstructure in the body and splenium of the corpus callosum (all t > 3.03, all p < .05). Our findings suggest that an attention-related component process of emotion regulation is disrupted in children treated for brain tumors, and that it may relate to their emotional difficulties and WM organization. This work provides a foundation for future theoretical and mechanistic investigations of emotional difficulties in brain tumor survivors.

It is well known that we continuously filter incoming sensory information, selectively allocating attention to what is important while suppressing distracting or irrelevant information. Yet questions remain about spatiotemporal patterns of neural processes underlying attentional biases toward emotionally significant aspects of the world. One index of affectively biased attention is an emotional variant of an attentional blink (AB) paradigm, which reveals enhanced perceptual encoding for emotionally salient over neutral stimuli under conditions of limited executive attention. The present study took advantage of the high spatial and temporal resolution of magnetoencephalography (MEG) to investigate neural activation related to emotional and neutral targets in an AB task. MEG data were collected while participants performed a rapid stimulus visual presentation task in which two target stimuli were embedded in a stream of distractor words. The first target (T1) was a number and the second (T2) either an emotionally salient or neutral word. Behavioural results replicated previous findings of greater accuracy for emotionally salient than neutral T2 words. MEG source analyses showed that activation in orbitofrontal cortex, characterized by greater power in the theta and alpha bands, and dorsolateral prefrontal activation were associated with successful perceptual encoding of emotionally salient relative to neutral words. These effects were observed between 250 and 550 ms, latencies associated with discrimination of perceived from unperceived stimuli. These data suggest that important nodes of both emotional salience and frontoparietal executive systems are associated with the emotional modulation of the attentional blink.

The study of binary Kuiper Belt objects helps to probe the dynamic conditions present during planet formation in the solar system. We report on the mutual-orbit determination of 2001 QW322, a Kuiper Belt binary with a very large separation whose properties challenge binary-formation and -evolution theories. Six years of tracking indicate that the binary's mutual-orbit period is approximately 25 to 30 years, that the orbit pole is retrograde and inclined 50 degrees to 62 degrees from the ecliptic plane, and, most surprisingly, that the mutual orbital eccentricity is <0.4. The semimajor axis of 105,000 to 135,000 kilometers is 10 times that of other near-equal-mass binaries. Because this weakly bound binary is prone to orbital disruption by interlopers, its lifetime in its present state is probably less than 1 billion years.

Background Genomics enables individualized diagnosis and treatment, but large challenges remain to functionally interpret rare variants. To date, only one causative variant has been described for KCNK9 imprinting syndrome (KIS). The genotypic and phenotypic spectrum of KIS has yet to be described and the precise mechanism of disease fully understood. Methods This study discovers mechanisms underlying KCNK9 imprinting syndrome (KIS) by describing 15 novel KCNK9 alterations from 47 KIS-affected individuals. We use clinical genetics and computer-assisted facial phenotyping to describe the phenotypic spectrum of KIS. We then interrogate the functional effects of the variants in the encoded TASK3 channel using sequence-based analysis, 3D molecular mechanic and dynamic protein modeling, and in vitro electrophysiological and functional methodologies. Results We describe the broader genetic and phenotypic variability for KIS in a cohort of individuals identifying an additional mutational hotspot at p.Arg131 and demonstrating the common features of this neurodevelopmental disorder to include motor and speech delay, intellectual disability, early feeding difficulties, muscular hypotonia, behavioral abnormalities, and dysmorphic features. The computational protein modeling and in vitro electrophysiological studies discover variability of the impact of KCNK9 variants on TASK3 channel function identifying variants causing gain and others causing loss of conductance. The most consistent functional impact of KCNK9 genetic variants, however, was altered channel regulation. Conclusions This study extends our understanding of KIS mechanisms demonstrating its complex etiology including gain and loss of channel function and consistent loss of channel regulation. These data are rapidly applicable to diagnostic strategies, as KIS is not identifiable from clinical features alone and thus should be molecularly diagnosed. Furthermore, our data suggests unique therapeutic strategies may be needed to address the specific functional consequences of KCNK9 variation on channel function and regulation.

The study of binary Kuiper Belt objects helps to probe the dynamic conditions present during planet formation in the solar system. We report on the mutual-orbit determination of 2001 QW₃₂₂, a Kuiper Belt binary with a very large separation whose properties challenge binary-formation and -evolution theories. Six years of tracking indicate that the binary's mutual-orbit period is ≈25 to 30 years, that the orbit pole is retrograde and inclined 50° to 62° from the ecliptic plane, and, most surprisingly, that the mutual orbital eccentricity is <0.4. The semimajor axis of 105,000 to 135,000 kilometers is 10 times that of other near-equal-mass binaries. Because this weakly bound binary is prone to orbital disruption by interlopers, its lifetime in its present state is probably less than 1 billion years.

The study of binary Kuiper Belt objects helps to probe the dynamic conditions present during planet formation in the solar system. We report on the mutual-orbit determination of 2001 QW 322 , a Kuiper Belt binary with a very large separation whose properties challenge binary-formation and -evolution theories. Six years of tracking indicate that the binary's mutual-orbit period is ≈25 to 30 years, that the orbit pole is retrograde and inclined 50° to 62° from the ecliptic plane, and, most surprisingly, that the mutual orbital eccentricity is <0.4. The semimajor axis of 105,000 to 135,000 kilometers is 10 times that of other near-equal-mass binaries. Because this weakly bound binary is prone to orbital disruption by interlopers, its lifetime in its present state is probably less than 1 billion years.

orbit determination of 2001 QW 322 , a Kuiper Belt binary with a very large separation whose properties challenge binary-formation and evolution theories. Six years of tracking indicate that the binary's mutual orbit period is ≈25-30 years, that the orbit pole is retrograde and inclined 50-62 • from the ecliptic plane, and, most surprisingly, that the mutual orbital eccentricity is < 0.4. The semimajor axis of 105,000-135,000 km is 10 times that of other near-equal mass binaries. Because this weakly bound binary is prone to or-bital disruption by interlopers, its lifetime in its present state is likely less than 1

Of 89 patients receiving nightly subcutaneous deferoxamine for transfusion-dependent thalassemia major or Diamond–Blackfan anemia, 13 presented with visual loss or deafness of acute onset or both. Detailed ophthalmologic, audiologic, and evoked-potential studies uncovered abnormalities caused by neurotoxicity in 27 more. Four patients with visual loss had optic neuropathy, with a marked decrease in acuity, loss of color vision, and delayed visual evoked potentials. Five asymptomatic patients had changes in the pigment of the retinal epithelium. The hearing loss was characterized by a high-frequency sensorineural deficit, which necessitated hearing aids in six patients. When deferoxamine was stopped, recovery of vision was complete in 2 patients and partial in 2, and in 22 patients with abnormal audiograms, reversal of the hearing deficit was complete in 4 and partial in 1. An analysis of the clinical data showed that members of the affected group were younger, had lower serum ferritin values, and were self-administering higher doses of deferoxamine per kilogram of body weight. Significantly lower doses of deferoxamine were being taken by patients without abnormalities than by those with visual symptoms, abnormal audiograms, or prolonged evoked potentials (P<0.001, <0.006, and <0.04, respectively). The data implicate high-dose deferoxamine as a central factor in the pathogenesis of the neurotoxicity. We strongly recommend careful regulation of the deferoxamine dosage and serial audiovisual monitoring in all patients receiving the drug. (N Engl J Med 1986; 314: 869–73.) GENERALIZED iron loading due to multiple transfusions is common in β-thalassemia major and steroid-unresponsive Diamond–Blackfan anemia. Since 1962, when administration of intramuscular deferoxamine was shown to increase urinary iron excretion substantially in patients with thalassemia, 1 determined efforts have been made worldwide to administer parenteral deferoxamine for chelation in parallel with transfusions. Intramuscular injections of deferoxamine have since been replaced by subcutaneous infusion for home-care use. Over the years, deferoxamine has remained the most efficient iron-chelating agent available, and because it has been regarded as having minimal side effects, recommendations for more intensive, daily administration have generally been accepted. We report . . .