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Significance Increased rates of smoking cessation will be essential to maximize the population benefit of low-dose CT screening for lung cancer. The NCI’s Smoking Cessation at Lung Examination (SCALE) Collaboration includes eight randomized trials, each assessing evidence-based interventions among smokers undergoing lung cancer screening (LCS). We examined predictors of trial enrollment to improve future outreach efforts for cessation interventions offered to older smokers in this and other clinical settings. Methods We included the six SCALE trials that randomized individual participants. We assessed demographics, intervention modalities, LCS site and trial administration characteristics, and reasons for declining. Results Of 6285 trial- and LCS-eligible individuals, 3897 (62%) declined and 2388 (38%) enrolled. In multivariable logistic regression analyses, Blacks had higher enrollment rates (OR 1.5, 95% CI 1.2,1.8) compared to Whites. Compared to “NRT Only” trials, those approached for “NRT + prescription medication” trials had higher odds of enrollment (OR 6.1, 95% CI 4.7,7.9). Regarding enrollment methods, trials using “Phone + In Person” methods had higher odds of enrollment (OR 1.6, 95% CI 1.2,1.9) compared to trials using “Phone Only” methods. Some of the reasons for declining enrollment included “too busy” (36.6%), “not ready to quit” (8.2%), “not interested in research” (7.7%), and “not interested in the intervention offered” (6.2%). Conclusion Enrolling smokers in cessation interventions in the LCS setting is a major priority that requires multiple enrollment and intervention modalities. Barriers to enrollment provide insights that can be addressed and applied to future cessation interventions to improve implementation in LCS and other clinical settings with older smokers. Implications We explored enrollment rates and reasons for declining across six smoking cessation trials in the lung cancer screening setting. Offering multiple accrual methods and pharmacotherapy options predicted increased enrollment across trials. Enrollment rates were also greater among Blacks compared to Whites. The findings offer practical information for the implementation of cessation trials and interventions in the lung cancer screening context and other clinical settings, regarding intervention modalities that may be most appealing to older, long-term smokers.

As one of the Arctic Council’s permanent observer states, South Korea has implemented various policies related to the Arctic despite its significant geographical and cultural distance from the Arct...

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach.

We investigated efficacy of in ovo application of epidermal growth factor (EGF) on intestinal expression of EGF receptor (EGFR) during embryogenesis (experiment 1) and posthatch growth performance and gastrointestinal development in broiler chickens (experiment 2). In experiment 1, 450 fertile Ross 708 eggs were allocated to 3 groups (150 eggs/group): 1) control, 2) 160 μg EGF/kg of egg, and 3) 640 μg of EGF/kg of egg. Eggs were candled for live embryos on day 16 and injected with the respective treatment solutions on day 17 and sampled for jejunal tissue from day 17 to hatch for EGFR analyses. There was no effect of EGF (P > 0.05) on EGFR expression on day 17 to 20; however, on day 21, EGF increased (P < 0.05) EGFR expression in EGF birds relative to control birds. In experiment 2, 600 fertile Ross 708 eggs were allocated to 5 treatments: 1) intact, no puncture or injection, 2) punched but not injected, 3) control, no EGF, 4) 80 μg of EGF/kg of egg, and 5) 160 μg of EGF/kg of egg. The eggs were incubated and candled for live embryos on D 19, treated, and subsequently transferred to the hatcher. Upon hatching, chicks were weighed, and 90 chicks per treatment placed in cages (15 birds/cage) and allowed free access to a standard antibiotic-free corn-soybean diet for 21 D. Feed intake and body weight were monitored on a weekly basis. Samples of birds were necropsied on D 0, 7, 14, and 21 for measurements of intestinal weight and jejunal histomorphology and excreta samples taken on D 3 to 5 and 17 to 19 for apparent retention of dry matter. There was no EGF effect (P > 0.05) on any posthatch response criteria. In conclusion, in ovo application of EGF increased EGFR expression but had no effect on posthatch growth performance, DM retention, and intestinal development. The lack of EGF effect on posthatch response was surprising but suggested in ovo application of EGF may not be a viable approach.

The effect of Eimeria challenge on standardized ileal digestibility (SID) of amino acids (AA) in major poultry feed ingredients fed to broiler chickens was determined. A total of 840 male 9-day-old Ross 708 chicks were placed in 84 cages (10 birds/cage) and allocated to either a nitrogen-free diet (NFD) or one of the 6 test diets based on a single or mixture of feed ingredients as the sole source of AA (n = 12). Test diets were: 1) corn, 2) wheat, 3) soybean meal (SBM), 4) pork meal (PM), 5) corn, SBM, and PM (CSP), and 6) wheat, SBM, and PM (WSP). On d 10, birds in 6 cages/diet were orally gavaged with 1 mL of E. acervulina and E. maxima mixture and the other 6 cages with sham. On d 15, birds were bled for plasma AA and necropsied for intestinal lesion scores and ileal digesta samples. Challenge decreased (P0.05) plasma concentration of Arg, His, Thr, Asp, Gln, and Tyr and increased concentration of Lys, Ile, Leu, and Val. There was a diet by challenge interaction (P0.05) on intestinal lesion scores with birds fed mixed diets exhibiting more severe lesions than birds fed single ingredient diets. Diet by challenge interacted (P0.05) on ileal total endogenous flow (ITEF) of AA except for Arg, Met, Ala, Asp, and Cys, such that challenged birds fed the mixed, particularly WSP, had higher ITEF of AA compared to single ingredients birds. Diet and challenge interaction (P0.05) was observed for SID of Arg, Thr, Val, Glu, and Gly. Challenge decreased (P0.05) SID of most AA except for Met, Asp, and Cys with the largest impact seen on Lys, His, Ser, and Thr. With exception of Arg, Thr, Asp, and Cys, birds fed mixed diets had higher (P0.05) SID values compared to birds fed single ingredients. In conclusion, Eimeria reduced plasma availability and ileal digestibility of most AA. However, challenge interaction with diet composition on SID of some AA warrants further investigations.

BACKGROUND Intraventricular brain tumors make up only 0.9–4.5% of all cases of metastatic brain cancer.1 Involvement of the choroid plexus (CP) is even rarer with only a handful of documented cases. 2,3 Here we describe a case of bilateral multifocal metastasis to the choroid plexus appearing 10 years after nephrectomy in a male with stage IV renal cell carcinoma (RCC). CASE PRESENTATION: Our patient is a 74-year-old male with stage IV RCC diagnosed in 2006 and treated with radical nephrectomy and immunotherapy in 2011. In 2020, he presented to the emergency department with altered mental status. Brain magnetic resonance imaging (MRI) revealed an enhancing hemorrhagic lesion in the trigone of the right lateral ventricle (LV) and nodular thickening in the center of the right LV and trigone of the left LV, suggestive of metastatic disease. In 2021, the patient developed refractory seizures, and serial MRIs showed disease progression. He underwent several craniotomies with pathology confirming metastatic clear cell carcinoma, consistent with a renal primary. In 2022, the patient again presented with altered mental status. MRI revealed new avidly enhancing subcentimeter solid nodules in the CP of both LVs consistent with metastatic disease. Per the wishes of the family, palliative measures were pursued, and the patient was discharged home. CONCLUSION RCC can reappear several years after nephrectomy. 4 Metastatic RCC appears to have a unique propensity to spread to the ventricular system and the CP, which indicates late progression of disease. 1,5,6 While surgery may be viable if tumor burden is low, therapeutic options are limited in the advanced disease stages, as in our patient. Palliative care should be offered early to maximize remaining quality of life.

Von Hippel–Lindau disease (VHL) is a hereditary disorder associated with malignant tumors including clear cell renal cell carcinoma (ccRCC). Partial nephrectomy is complicated by multilocular tumor occurrence and a high recurrence rate. The aim of this study was to evaluate the potential of stereotactic body radiotherapy (SBRT) as an alternative treatment approach in VHL patients with multiple ccRCC. Patients with VHL and a diagnosis of ccRCC were enrolled. SBRT was conducted using five fractions of 10 Gy or eight fractions of 7.5 Gy. The primary endpoint was local control (LC). Secondary endpoints included alteration of renal function and adverse events. Seven patients with a total of eight treated lesions were enrolled. Median age was 44 years. Five patients exhibited multiple bilateral kidney cysts in addition to ccRCC. Three patients underwent at least one partial nephrectomy in the past. After a median follow-up of 43 months, 2-year LC was 100%, while 2-year CSS, 2-year PFS and 2-year OS was 100%, 85.7% and 85.7%, respectively. SBRT was very well tolerated with no acute or chronic toxicities grade ≥ 2. Mean estimated glomerular filtration rate (eGFR) at baseline was 83.7 ± 13.0 mL/min/1.73 m2, which decreased to 76.6 ± 8.0 mL/min/1.73 m2 after 1 year. Although the sample size was small, SBRT resulted in an excellent LC rate and was very well tolerated with preservation of kidney function in patients with multiple renal lesions and cysts.

To understand the extent to which a policy instrument's early adoption is crucial in crisis management, we leverage unique worldwide data that record the daily evolution of policy mandate adoptions and COVID-19 infection and mortality rates. The analysis shows that the mask mandate is consistently associated with lower infection rates in the short term, and its early adoption boosts the long-term efficacy. By contrast, the other five policy instruments?domestic lockdowns, international travel bans, mass gathering bans, and restaurant and school closures?show weaker efficacy. Governments prepared for a public health crisis with stronger resilience or capacity and those with stronger collectivist cultures were quicker to adopt nationwide mask mandates. From a policy design perspective, policymakers must avoid overreacting with less effective instruments and underreacting with more effective ones during uncertain times, especially when interventions differ in efficacy and cost. This article is protected by copyright. All rights reserved.

We report an early-onset autosomal-recessive neurological disease with cerebellar atrophy and lysosomal dysfunction. We identified bi-allelic loss-of-function (LoF) variants in Oxidative Resistance 1 (OXR1) in five individuals from three families; these individuals presented with a history of severe global developmental delay, current intellectual disability, language delay, cerebellar atrophy, and seizures. While OXR1 is known to play a role in oxidative stress resistance, its molecular functions are not well established. OXR1 contains three conserved domains: LysM, GRAM, and TLDc. The gene encodes at least six transcripts, including some that only consist of the C-terminal TLDc domain. We utilized Drosophila to assess the phenotypes associated with loss of mustard (mtd), the fly homolog of OXR1. Strong LoF mutants exhibit late pupal lethality or pupal eclosion defects. Interestingly, although mtd encodes 26 transcripts, severe LoF and null mutations can be rescued by a single short human OXR1 cDNA that only contains the TLDc domain. Similar rescue is observed with the TLDc domain of NCOA7, another human homolog of mtd. Loss of mtd in neurons leads to massive cell loss, early death, and an accumulation of aberrant lysosomal structures, similar to what we observe in fibroblasts of affected individuals. Our data indicate that mtd and OXR1 are required for proper lysosomal function; this is consistent with observations that NCOA7 is required for lysosomal acidification.

Lung cancer mortality can be reduced by 20% via low dose CT lung cancer screening (LCS) and treatment of early-stage disease. Providing tobacco use treatment to high risk cigarette smokers in the LCS setting may result in health benefits beyond the impact of LCS. As one of the nine trials in the National Cancer Institute's Smoking Cessation at Lung Examination (SCALE) collaboration, the goal of the Lung Screening, Tobacco, and Health (LSTH) trial is to develop a scalable and cost-effective cessation intervention for subsequent implementation by LCS programs. Guided by the RE-AIM Framework, the LSTH trial is a two-arm RCT ( N = 1330) enrolling English- and Spanish-speaking smokers registered for LCS at one of seven collaborating sites. Participants are randomly assigned to Usual Care (UC; three proactive telephone counseling sessions/two weeks of nicotine patches) vs. Intensive Telephone Counseling (ITC; eight proactive sessions/eight weeks of nicotine patches, plus discussion of the LCS results to increase motivation to quit). Telephone counseling is provided by tobacco treatment specialists. To increase continuity of care, referring physicians are notified of participant enrollment and smoking status following the intervention. Outcomes include: 1) self-reported 7-day, 30-day, and sustained abstinence, and biochemically-verified at 3-, 6-, and 12-months post-randomization, 2) reach and engagement of the interventions, and 3) cost-effectiveness of the interventions. The Cancer Intervention and Surveillance Modeling Network (CISNET) will model long-term impacts of six SCALE trials on the cost per life year saved, quality-adjusted life years saved, lung cancer mortality reduction, and population mortality. Clinical trials registration The trial is registered at clinical trials.gov : NCT03200236 .

Older individuals who smoke are at increased risk of having severe outcomes from COVID-19, due to their long-term smoking and underlying health conditions. In this qualitative study, we explored the impact of COVID-19 on attitudes toward smoking and motivation to quit. Participants (N = 30) were enrolled in a larger ongoing randomized controlled smoking cessation trial conducted in the lung cancer screening setting. From March to May 2020, we assessed quantitative and qualitative responses to participants’ overall concern about COVID-19, changes in amount smoked, and motivation to reduce/quit smoking. Responses to the quantitative questions indicated that 64.3% of participants were extremely concerned with COVID-19, 20.7% reported reductions in amount smoked, and 37.9% reported increased motivation to quit. The qualitative responses, which were transcribed and coded using Consensual Qualitative Research guidelines, expanded upon these findings by providing the content of participants’ concerns, which included perceived risk of contracting COVID-19, the added stressors caused by COVID-19, and a variable impact on the amount smoked and motivation to quit. Although half of participants expressed extreme concern regarding COVID-19, fewer indicated increased motivation or reduced smoking. Qualitative themes suggested that the initial two months of the pandemic prompted some smokers to reduce or quit, but it exacerbated smoking triggers for others. Understanding how the pandemic continues to affect this vulnerable group will aid in adapting methods to support their efforts to stop smoking and remain abstinent.

How do different government mandates compare in their short and long-term efficacies in curbing COVID-19 infections? Does a mandate’s early adoption enhance its eventual efficacy? Using worldwide data on the daily evolution of government mandate adoptions and COVID-19 infections from January to July 2020, we found that, compared with five other commonly adopted mandates, early adoption of the mask mandate has the strongest short and long-term effect on curbing infections. Mass gathering bans and school closures have some effect but take more time to manifest their efficacy. Domestic lockdowns and restaurant closures have the least effect. When designing measures for curbing COVID-19 infections, governments must weigh the timing and relative efficacies of alternative policy instruments.

Prior research documents that analyst revisions are important information events and that some investors trade ahead of them. However, prior studies have been unable to show which investors trade ahead of analyst revisions, the aggregate benefits to trading ahead, and the costs borne by various investors from trading against investors that anticipate revisions. To address these questions, we exploit high-frequency trading information from the Korea Exchange (KRX) that characterizes all purchase and sale transactions of twenty different investor groups. We first validate that analyst revisions contain valuable private information: upgrades increase prices by 2.5% and downgrades decrease prices by 2.9%. We next document that asset managers who are geographically and socially close to analysts anticipate recommendations up to two days before they are released, while other institutions do not. Lastly, we show that this ability to anticipate analyst revisions enables these investors to trade profitably against domestic retail investors and foreign professional investors. Local hedge funds earn $2.5 million more than normal when trading against foreign professionals ahead of analyst revisions, which is more than all other investor groups combined. Notably, local asset managers typically lose money when trading against foreign professionals, who seem to earn profits by engaging in high-frequency market making. In sum, asset managers in Korea appear to receive tips from brokerages about upcoming revisions, which shifts the competitive balance between domestic institutions and skilled foreign market makers, and aggregate profits around revisions depend on investor sophistication, geographic proximity, and cultural affinity.

Collecting data with infants is notoriously difficult. As a result, many of our studies consist of small samples, with only a single measure, in a single age group, at a single time point. With renewed calls for greater academic rigor in data collection practices, using multiple outcome measures in infant research is one way to increase rigor, and at the same time, enable us to more accurately interpret our data. Here, we illustrate the importance of using multiple measures in psychological research with examples from our own work on rapid threat detection, and from the broader infancy literature. First, we describe our initial studies using a single outcome measure, and how this strategy caused us to nearly miss a rich and complex story about attention biases for threat and their development. We demonstrate how using converging measures can help researchers make inferences about infant behavior, and how using additional measures allows us to more deeply examine the mechanisms that drive developmental change. Finally, we provide practical and statistical recommendations for how researchers can use multiple measures in future work.

Although there is a large and growing literature on children's developing concepts of illness transmission, little is known about how children develop contagion knowledge before formal schooling begins and how these informal learning experiences can impact children's health behaviors. Here, we asked two important questions: first, do children's informal learning experiences, such as their experiences reading storybooks, regularly contain causal information about illness transmission; and second, what is the impact of this type of experience on children's developing knowledge and behavior? In Study 1, we examined whether children's commercial books about illness regularly contain contagion-relevant causal information. In Study 2, we ran a pilot study examining whether providing children with causal information about illness transmission in a storybook can influence their knowledge and subsequent behavior when presented with a contaminated object. The results from Study 1 suggest that very few (15%) children's books about illness feature biological causal mechanisms for illness transmission. However, results from Study 2 suggest that storybooks containing contagion-relevant explanations about illness transmission may encourage learning and avoidance of contaminated objects. Altogether, these results provide preliminary data suggesting that future research should focus on engaging children in learning about contagion and encouraging adaptive health behaviors.

Introduction Changing demographics have created substantial unmet needs for mental health and physical disability services for immigrant and racial/ethnic minority elders. Workforce shortages can be reduced by task-shifting to community health workers (CHWs) who speak the same language and share the culture of these elders. Yet, implementation of interventions offered by CHWs requires adaptations of content and delivery, ideally under clinical supervision. Objective To culturally adapt two evidence-based interventions, offered in community settings, to address mental health and physical disability prevention for diverse minority elders. Methods We followed the Castro-Barrera stepped model for cultural adaptation of two evidence-based interventions into one combined program of disability management and prevention delivered by CHWs. We used feedback from key stakeholders, including four clinical supervisors, 16 CHWs, 17 exercise trainers, and 153 participants, collected at three time points to further adapt the intervention to a diverse population of elders. Results Adaptations for administration by CHWs/exercise trainers included: systematization of supervision process, increased flexibility in sessions offered per participants’ needs, inclusion of self-care content, modification of materials to better reflect elders’ daily life experiences, and greater focus on patient engagement in care. Areas for additional adaptation included enhancing examples with culturally relevant metaphors, incorporating visual aids, and training CHWs in the importance of building trust. Conclusion This study identifies key aspects of the cultural adaptation process that facilitates broader cultural sensitivity of service delivery by CHWs to diverse elders in community settings.

Titin is a large filamentous protein that spans half a sarcomere, from Z‐disk to M‐line. The N2A region within the titin molecule exists between the proximal immunoglobulin (Ig) region and the PEVK region and protein–protein interactions involving this region are required for normal muscle function. The N2A region consists of four Ig domains (I80–I83) with a 105 amino acid linker region between I80 and I81 that has a helical nature. Using chemical stability measurements, we show that predicted differences between the adjacent Ig domains (I81–I83) correlate with experimentally determined differences in chemical stability and refolding kinetics. Our work further shows that I83 has the lowest ΔG (unfolding), which is increased in the presence of calcium (pCa 4.3), indicating that Ca(2+) plays a role in stabilizing this immunoglobulin domain. The characteristics of N2A's three Ig domains provide insight into the stability of the binding sites for proteins that interact with the N2A region. This work also provides insights into how Ca(2+) might influence binding events involving N2A.

Protestants were more likely than non-Protestants to demonstrate phenomena consistent with the use of reaction formation. Lab experiments showed that when manipulations were designed to produce taboo attractions (to unconventional sexual practices), Protestants instead showed greater repulsion. When implicitly conditioned to produce taboo repulsions (to African Americans), Protestants instead showed greater attraction. Supportive evidence from other studies came from clinicians' judgments, defense mechanism inventories, and a survey of respondent attitudes. Other work showed that Protestants who diminished and displaced threatening affect were more likely to sublimate this affect into creative activities; the present work showed that Protestants who do not or cannot diminish or displace such threatening affect instead reverse it. Traditional individual difference variables showed little ability to predict reaction formation, suggesting that the observed processes go beyond what we normally study when we talk about self-control. (PsycINFO Database Record

In July 2019, the Trump administration began implementing its domestic gag rule to ban discussion of abortion in pregnancy options counseling and ensure physical separation of contraceptive and abortion services at clinical sites funded by the federal government's Title X Family Planning program. In this paper, we examine how organizational policy utilization correlated with organization-level protocols for discussing abortion in options counseling interactions while the domestic gag rule policy was under legal contest. From April 2018 to July 2019, we conducted in-depth interviews with 50 administrators in charge of setting clinical protocols regarding options counseling after a positive pregnancy test at 20 Title X-covered and 14 non-Title X-covered safety-net healthcare organizations in Ohio. We found that organizational characteristics and Title X policy utilization did not explain the heterogeneity in approaches to abortion referral that administrators reported. Administrators from 2 of 20 organizations covered by Title X policy requirements pre-emptively restricted discussion of abortion in their facilities in advance of policy enactment. Meanwhile, administrators from 10 of 14 non-Title X-covered organizations did not restrict discussion of abortion. Our analysis demonstrates how safety-net healthcare organizations' response to federal policy is shaped by administrators' institutional entrepreneurship within the abortion aversion complex: a pattern of policy miscomprehension and endorsed abortion stigma that facilitates the structural stigmatization of abortion within safety-net healthcare organizations. We conclude that current efforts to reverse the domestic gag rule will fail unless local abortion aversion complexes are targeted with intervention.

Significance Although it is a requirement that tobacco treatment is offered to cigarette smokers undergoing low-dose computed tomographic lung cancer screening (LCS), not all smokers engage in treatment. To understand the barriers to tobacco treatment in this setting, we evaluated predictors of attrition in a smoking cessation trial among individuals undergoing LCS. Methods Prior to LCS, 926 participants, 50–80 years old, completed the baseline (T0) phone assessment, including demographic, clinical, tobacco, and psychological characteristics. Following LCS and receipt of the results, participants completed the pre-randomization (T1) assessment. Results At the T1 assessment, 735 (79%) participants were retained and 191 (21%) dropped out. In multivariable analyses, attrition was higher among those who: smoked >1 pack per day (OR = 1.44, CI 1.01, 2.06) or had undergone their first (vs. annual) LCS scan (OR = 1.70, CI 1.20, 2.42). Attrition was lower among those with: more education (associates (OR = 0.67, CI = 0.46, 0.98) or bachelor's degree (OR = 0.56, CI 0.35, 0.91) vs. high school/GED), some (vs. none/a little) worry about lung cancer (OR = 0.60, CI 0.39, 0.92), or a screening result that was benign (OR = 0.57, CI 0.39, 0.82) or probably benign (OR = 0.38, CI 0.16, 0.90) vs. negative. Conclusions This study illuminated several LCS-related factors that contributed to trial attrition. Increasing tobacco treatment in this setting will require targeted strategies for those who. report little lung cancer worry, are undergoing their first LCS exam, and/or who have a negative LCS result. Addressing attrition and reducing barriers to tobacco treatment will increase. the likelihood of cessation, thereby reducing the risk of developing lung cancer.

Western culture has 2 contradictory images of creativity: the artist as intensely emotional versus the artist as sublimator, for whom work becomes the outlet for what is repressed and denied. We show that both images are correct, but that the routes to creativity are culturally patterned, such that Catholic creatives are relatively more likely to take the emotionally intense route and Protestant creatives relatively more likely to take the sublimating route. This pattern is consistent for both the Big-C creativity of historical eminents (Studies 1 and 1b) and small-c creativity of student samples (Studies 2 and 3). The student samples also highlighted the moderating role of Protestant asceticism, as Protestants who were high in asceticism and who also repressed or minimized troublesome emotions were particularly creative. Analyses of behavioral data in previous lab experiments (Studies 2b and 3b) provided conceptual validation of the findings reported in Studies 2 and 3. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

In this chapter, we will provide an overview of the development of fear across infancy and early childhood. First, we describe various theoretical accounts of emotion and their implications for studying fear across development. Next, we describe the perception of threat, including how infants and young children first come to recognize and differentiate a fearful face from other emotional expressions and when they begin to detect signals of threat in the environment. We then describe the developmental trajectory of fearful behavior starting with infancy. We discuss the most commonly experienced fears from infancy to adulthood and how these fears might be acquired. Finally, we describe the neurological underpinnings of fear learning throughout development and close with a few thoughts on future directions for studying fear over the life span.

Mitochondrial DNA maintenance (mtDNA) defects have a wide range of causes, each with a set of phenotypes that overlap with many other neurological or muscular diseases. Clinicians face the challenge of narrowing down a long list of differential diagnosis when encountered with non-specific neuromuscular symptoms. Biallelic pathogenic variants in the Thymidine Kinase 2 (TK2) gene cause a myopathic form of mitochondrial DNA maintenance defect. Since the first description in 2001, there have been 71 patients reported with 42 unique pathogenic variants. Here we are reporting 11 new cases with 5 novel pathogenic variants. We describe and analyze a total of 82 cases with 47 unique TK2 pathogenic variants in effort to formulate a comprehensive molecular and clinical spectrum of TK2-related mtDNA maintenance disorders.