Hemispheric dominance in HVC is experience-dependent in juvenile male zebra finches.

Juvenile male zebra finches (Taeniopygia guttata) must be exposed to an adult tutor during a sensitive period to develop normal adult song. The pre-motor nucleus HVC (acronym used as a proper name), plays a critical role in song learning and production (cf. Broca's area in humans). In the human brain, left-side hemispheric dominance in some language regions is positively correlated with proficiency in linguistic skills. However, it is unclear whether this pattern depends upon language learning, develops with normal maturation of the brain, or is the result of pre-existing functional asymmetries. In juvenile zebra finches, even though both left and right HVC contribute to song production, baseline molecular activity in HVC is left-dominant. To test if HVC exhibits hemispheric dominance prior to song learning, we raised juvenile males in isolation from adult song and measured neuronal activity in the left and right HVC upon first exposure to an auditory stimulus. Activity in the HVC was measured using the immediate early gene (IEG) zenk (acronym for zif-268, egr-1, NGFI-a, and krox-24) as a marker for neuronal activity. We found that neuronal activity in the HVC of juvenile male zebra finches is not lateralized when raised in the absence of adult song, while normally-reared juvenile birds are left-dominant. These findings show that there is no pre-existing asymmetry in the HVC prior to song exposure, suggesting that lateralization of the song system depends on learning through early exposure to adult song and subsequent song-imitation practice.

Radioembolization plus Immune Checkpoint Inhibitor Therapy Compared with Radioembolization plus Tyrosine Kinase Inhibitor Therapy for the Treatment of Hepatocellular Carcinoma.

PURPOSE: To investigate if combination therapy with immune checkpoint inhibitor (ICI) and yttrium-90 (90Y) radioembolization results in superior outcomes than those yielded by tyrosine kinase inhibitor (TKI) therapy and 90Y for the treatment of intermediate- to advanced-stage hepatocellular carcinoma (HCC). METHODS: A retrospective review of patients presented at an institutional multidisciplinary liver tumor board between January 1, 2012 and August 1, 2023 was conducted. In total, 44 patients with HCC who underwent 90Y 4 weeks within initiation of ICI or TKI therapy were included. Propensity score matching was conducted to account for baseline demographic differences. Kaplan-Meier analysis was used to compare median progression-free survival (PFS) and overall survival (OS), and univariate statistics identified disease response and control rate differences. Duration of imaging response was defined as number of months between the first scan after therapy and the first scan showing progression as defined by modified Response Evaluation Criteria in Solid Tumors (mRECIST) or immune Response Evaluation Criteria in Solid Tumors (iRECIST). Adverse events were analyzed per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: Patients in the 90Y+ICI therapy group had better objective response rates (ORRs) (89.5% vs 36.8%; P < .001) and disease control rates (DCRs) (94.7% vs 63.2%; P < .001) by mRECIST and iRECIST (ORR: 78.9% vs 36.8%; P < .001; DCR: 94.7% vs 63.2%; P < .001). Median PFS (8.3 vs 4.1 months; P = .37) and OS (15.8 vs 14.3 months; P = .52) were not statistically different. Twelve patients (63.1%) in the 90Y+TKI group did not complete systemic therapy owing to adverse effects compared with 1 patient (5.3%) in the 90Y+ICI group (P < .001). Grade 3/4 adverse events were not statistically different (90Y+TKI: 21.1%; 90Y+ICI: 5.3%; P = .150). CONCLUSIONS: Patients with HCC who received 90Y+ICI had better imaging response and fewer regimen-altering adverse events than those who received 90Y+TKI. No significant combination therapy adverse events were attributable to radioembolization.

Below-the-Knee Stents and Scaffolds: A Comprehensive Review.

Below-the-knee intervention of chronic limb-threatening ischemia is an area of increasing interest. Due to lower morbidity and possibly better clinical outcomes, endovascular techniques have become increasingly important in this patient population many of who have limited surgical options. This article serves as a review of existing stent and scaffolding devices utilized for infrapopliteal disease. The authors will additionally discuss current indications and review studies that are investigating novel materials used in treating infrapopliteal arterial disease.

BRCA1/2 Testing in Massachusetts Among Women With Private Insurance or Medicaid, 2011-2015.

PURPOSE: Testing for BRCA1/2 mutations has increased among privately insured women in the United States. However, little is known about testing rates or trends among women with Medicaid. We sought to determine whether BRCA1/2 testing rates differed between women with private insurance compared with women with Medicaid in a state where both insurance types cover the test, and to compare testing trends from 2011 to 2015. METHODS: We conducted a retrospective cohort study of medical claims from January 2011 through June 2015. We included Massachusetts women aged 18-64 with private insurance or Medicaid and at least 12 months of continuous enrollment. We used multivariable linear regression to examine the association of insurance type, age, and time with testing rates. RESULTS: Mean monthly BRCA1/2 testing rates were lower among women with Medicaid compared with those with private insurance. Among privately insured women, mean monthly rates rose from 9.3 per 100,000 in 2011 to 18.4 per 100,000 in 2015, while among Medicaid-insured women, rates increased from 3.7 to 14.7. There was no difference in the monthly rate of increase in both groups (P=0.07). In adjusted analyses, rates were lower among Medicaid-insured women (7 fewer tests per month than privately insured women, P<0.001), and differed by age, with women aged 44-54 most likely to receive testing and women 18-34 the least likely. CONCLUSION: BRCA1/2 testing rates were lower among women insured by Medicaid compared with those with private insurance, though rates increased from 2011 to 2015 among both groups of women at a similar rate.

Comparison of up-front cash cards and checks as incentives for participation in a clinician survey: a study within a trial.

BACKGROUND: Evidence is needed regarding effective incentive strategies to increase clinician survey response rates. Cash cards are increasingly used as survey incentives; they are appealing because of their convenience and because in some cases their value can be reclaimed by investigators if not used. However, their effectiveness in clinician surveys is not known. In this study within the BRCA Founder OutReach (BFOR) study, a clinical trial of population-based BRCA1/2 mutation screening, we compared the use of upfront cash cards requiring email activation versus checks as clinician survey incentives. METHODS: Participants receiving BRCA1/2 testing in the BFOR study could elect to receive their results from their primary care provider (PCP, named by the patient) or from a geneticist associated with the study. In order to understand PCPs' knowledge, attitudes, experiences and willingness to disclose results we mailed paper surveys to the first 501 primary care providers (PCPs) in New York, Boston, Los Angeles and Philadelphia who were nominated by study participants to disclose their BRCA1/2 mutation results obtained through the study. We used alternating assignment stratified by city to assign the first 303 clinicians to receive a $50 up-front incentive as a cash card (N = 155) or check (N = 148). The cash card required PCPs to send an activation email in order to be used. We compared response rates by incentive type, adjusting for PCP characteristics and study site. RESULTS: In unadjusted analyses, PCPs who received checks were more likely to respond to the survey than those who received cash cards (54.1% versus 41.9%, p = 0.046); this remained true when we adjusted for provider characteristics (OR for checks 1.61, 95% CI 1.01, 2.59). No other clinician characteristics had a statistically significant association with response rates in adjusted analyses. When we included an interaction term for incentive type and city, the favorable impact of checks on response rates was evident only in Los Angeles and Philadelphia. CONCLUSIONS: An up-front cash card incentive requiring email activation may be less effective in eliciting clinician responses than up-front checks. However, the benefit of checks for clinician response rates may depend on clinicians' geographic location. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT03351803 ), November 24, 2017.

Hemispheric dominance underlying the neural substrate for learned vocalizations develops with experience.

Many aspects of song learning in songbirds resemble characteristics of speech acquisition in humans. Genetic, anatomical and behavioural parallels have most recently been extended with demonstrated similarities in hemispheric dominance between humans and songbirds: the avian higher order auditory cortex is left-lateralized for processing song memories in juvenile zebra finches that already have formed a memory of their fathers' song, just like Wernicke's area in the left hemisphere of the human brain is dominant for speech perception. However, it is unclear if hemispheric specialization is due to pre-existing functional asymmetry or the result of learning itself. Here we show that in juvenile male and female zebra finches that had never heard an adult song before, neuronal activation after initial exposure to a conspecific song is bilateral. Thus, like in humans, hemispheric dominance develops with vocal proficiency. A left-lateralized functional system that develops through auditory-vocal learning may be an evolutionary adaptation that could increase the efficiency of transferring information within one hemisphere, benefiting the production and perception of learned communication signals.