Aging and Post-Intensive Care Syndrome–Family (PICS-F): A Critical Need for Geriatric Psychiatry

Postintensive care syndrome–family (PICS-F) describes the psychological symptoms that affect the family members of patients hospitalized in the intensive care unit (ICU) or recently discharged from the ICU. Geriatric psychiatrists should be concerned about PICS-F for several reasons. First, ICU hospitalization in older adults is associated with higher rates of cognitive and physical impairment compared with older adults hospitalized in non-ICU settings or dwelling in the community. This confers a special burden on the caregivers of these older ICU survivors compared with other geriatric populations. Second, as caregivers themselves age, caring for this unique burden can be more challenging compared with other geriatric populations. Third, evidence for models of care centered on patients with multimorbidity and their caregivers is limited. A deeper understanding of how to care for PICS and PICS-F may inform clinical practice for other geriatric populations with multimorbidity and their caregivers. Geriatric psychiatrists may play a key role in delivering coordinated care for PICS-F by facilitating timely diagnosis and interdisciplinary collaboration, advocating for the healthcare needs of family members suffering from PICS-F, and leading efforts within healthcare systems to increase awareness and treatment of PICS-F. This clinical review will appraise the current literature about the impact of critical illness on the family members of ICU survivors and identify crucial gaps in our knowledge about PICS-F among aging patients and caregivers

Information-theoretic content selection for automated home video editing

ABSTRACT In automated home video editing, selecting out the most informative contents from the redundant footage is challenging. This paper proposes an information-theoretic approach to content selection by exploring the dependence relations between who (characters) and where (scenes) in the video. First the footage is segmented into basic units about the same characters at the same scene. To compactly represent the dependence relations between scenes and characters, contingency table is used to model their co-occurrence statistics. Suppose the contents about which characters at which scene are dominating by two random variables, an optimal selection criterion is proposed based on joint entropy. To improve the computation efficiency, a pruned N-Best heuristic algorithm is presented to search the most informative video units. Experimental results demonstrated the proposed approach is flexible and effective for automated content selection

ρ(770)0\rho(770)^0, K∗(892)0^*(892)^0 and f0(980)_{0}(980) Production in Au-Au and pp Collisions at sNN\sqrt{s_{NN}} = 200 GeV

Preliminary results on $\rho(770)^0 \to \pi^{+}\pi^{-}$, K$^{*}(892)^{0} \to \pi$K and $f_{0}(980) \to \pi^{+}\pi^{-}$ production using the mixed-event technique are presented. The measurements are performed at mid-rapidity by the STAR detector in $\sqrt{s_{NN}}$= 200 GeV Au-Au and pp interactions at RHIC. The results are compared to different measurements at various energies.Comment: 4 pages, 6 figures. Talk presented at Quark Matter 2002, Nantes, France, July 18-24, 2002. To appear in the proceedings (Nucl. Phys. A

Glucagon regulates hepatic lipid metabolism via cAMP and Insig-2 signaling: implication for the pathogenesis of hypertriglyceridemia and hepatic steatosis

Insulin induced gene-2 (Insig-2) is an ER-resident protein that inhibits the activation of sterol regulatory element-binding proteins (SREBPs). However, cellular factors that regulate Insig-2 expression have not yet been identified. Here we reported that cyclic AMP-responsive element-binding protein H (CREBH) positively regulates mRNA and protein expression of a liver specific isoform of Insig-2, Insig-2a, which in turn hinders SREBP-1c activation and inhibits hepatic de novo lipogenesis. CREBH binds to the evolutionally conserved CRE-BP binding elements located in the enhancer region of Insig-2a and upregulates its mRNA and protein expression. Metabolic hormone glucagon and nutritional fasting activated CREBH, which upregulated expression of Insig-2a in hepatocytes and inhibited SREBP-1c activation. In contrast, genetic depletion of CREBH decreased Insig-2a expression, leading to the activation of SREBP-1c and its downstream lipogenic target enzymes. Compromising CREBH-Insig-2 signaling by siRNA interference against Insig-2 also disrupted the inhibitory effect of this signaling pathway on hepatic de novo triglyceride synthesis. These actions resulted in the accumulation of lipid droplets in hepatocytes and systemic hyperlipidemia. Our study identified CREBH as the first cellular protein that regulates Insig-2a expression. Glucagon activated the CREBH-Insig-2a signaling pathway to inhibit hepatic de novo lipogenesis and prevent the onset of hepatic steatosis and hypertriglyceridemia

Designing a tobacco counter-marketing campaign for African American youth

The objectives of this qualitative study were to: a) identify common marketing themes and tactics used by the tobacco industry to entice African Americans (AA's) and youth to initiate and maintain smoking behavior, especially smoking mentholated brands of cigarettes, and b) determine AA youths' knowledge, attitudes, intentions, and beliefs about smoking and the tobacco industry. Together, these activities could aid in the development of effective tobacco counter-marketing campaigns for AA youth. Using publicly available tobacco industry documents, computerized searches using standardized keywords were run and results were cataloged and analyzed thematically. Subsequently, 5 focus groups were conducted with n = 28 AA middle school-aged youth. Results suggest that the tobacco industry consistently recruited new AA smokers through a variety of means, including social and behavioral marketing studies and targeted media and promotional campaigns in predominantly AA, urban, and low income areas. AA youth interviewed in this study were largely unaware of these tactics, and reacted negatively against the industry upon learning of them. Youth tended to externalize control over tobacco, especially within the AA community. In designing a counter-marketing campaign for this population, partnering knowledge of tobacco industry practices with youth needs and community resources will likely increase their effectiveness

Comparative toxicity outcomes of proton-beam therapy versus intensity-modulated radiotherapy for prostate cancer in the postoperative setting

Background Despite increasing utilization of proton-beam therapy (PBT) in the postprostatectomy setting, no data exist regarding toxicity outcomes relative to intensity-modulated radiotherapy (IMRT). The authors compared acute and late genitourinary (GU) and gastrointestinal (GI) toxicity outcomes in patients with prostate cancer (PC) who received treatment with postprostatectomy IMRT versus PBT. Methods With institutional review board approval, patients with PC who received adjuvant or salvage IMRT or PBT (70.2 gray with an endorectal balloon) after prostatectomy from 2009 through 2017 were reviewed. Factors including combined IMRT and PBT and/or concurrent malignancies prompted exclusion. A case-matched cohort analysis was performed using nearest-neighbor 3-to-1 matching by age and GU/GI disorder history. Logistic and Cox regressions were used to identify univariate and multivariate associations between toxicities and cohort/dosimetric characteristics. Toxicity-free survival (TFS) was assessed using the Kaplan-Meier method. Results Three hundred seven men (mean +/- SD age, 59.7 +/- 6.3 years; IMRT, n = 237; PBT, n = 70) were identified, generating 70 matched pairs. The median follow-up was 48.6 and 46.1 months for the IMRT and PBT groups, respectively. Although PBT was superior at reducing low-range (volumes receiving 10% to 40% of the dose, respectively) bladder and rectal doses (all P = .05). Five-year grade >= 2 GU and grade >= 1 GI TFS was 61.1% and 73.7% for IMRT, respectively, and 70.7% and 75.3% for PBT, respectively; and 5-year grade >= 3 GU and GI TFS was >95% for both groups (all P >= .05). Conclusions Postprostatectomy PBT minimized low-range bladder and rectal doses relative to IMRT; however, treatment modality was not associated with clinician-reported GU/GI toxicities. Future prospective investigation and ongoing follow-up will determine whether dosimetric differences between IMRT and PBT confer clinically meaningful differences in long-term outcomes

Tissue Effects in a Randomized Controlled Trial of Short-term Finasteride in Early Prostate Cancer.

BackgroundIn the Prostate Cancer Prevention Trial, finasteride selectively suppressed low-grade prostate cancer and significantly reduced the incidence of prostate cancer in men treated with finasteride compared with placebo. However, an apparent increase in high-grade disease was also observed among men randomized to finasteride. We aimed to determine why and hypothesized that there is a grade-dependent response to finasteride.MethodsFrom 2007 to 2012, we randomized dynamically by intranet-accessible software 183 men with localized prostate cancer to receive 5mg finasteride or placebo daily in a double-blind study during the 4-6weeks preceding prostatectomy. As the primary end point, the expression of a predefined molecular signature (ERβ, UBE2C, SRD5A2, and VEGF) differentiating high- and low-grade tumors in Gleason grade (GG) 3 areas of finasteride-exposed tumors from those in GG3 areas of placebo-exposed tumors, adjusted for Gleason score (GS) at prostatectomy, was compared. We also determined androgen receptor (AR) levels, Ki-67, and cleaved caspase 3 to evaluate the effects of finasteride on the expression of its downstream target, cell proliferation, and apoptosis, respectively. The expression of these markers was also compared across grades between and within treatment groups. Logistic regression was used to assess the expression of markers.FindingsWe found that the predetermined molecular signature did not distinguish GG3 from GG4 areas in the placebo group. However, AR expression was significantly lower in the GG4 areas of the finasteride group than in those of the placebo group. Within the finasteride group, AR expression was also lower in GG4 than in GG3 areas, but not significantly. Expression of cleaved caspase 3 was significantly increased in both GG3 and GG4 areas in the finasteride group compared to the placebo group, although it was lower in GG4 than in GG3 areas in both groups.InterpretationWe showed that finasteride's effect on apoptosis and AR expression is tumor grade dependent after short-term intervention. This may explain finasteride's selective suppression of low-grade tumors observed in the PCPT

Molecular testing for the clinical diagnosis of fibrolamellar carcinoma.

Fibrolamellar carcinoma has a distinctive morphology and immunophenotype, including cytokeratin 7 and CD68 co-expression. Despite the distinct findings, accurate diagnosis of fibrolamellar carcinoma continues to be a challenge. Recently, fibrolamellar carcinomas were found to harbor a characteristic somatic gene fusion, DNAJB1-PRKACA. A break-apart fluorescence in situ hybridization (FISH) assay was designed to detect this fusion event and to examine its diagnostic performance in a large, multicenter, multinational study. Cases initially classified as fibrolamellar carcinoma based on histological features were reviewed from 124 patients. Upon central review, 104 of the 124 cases were classified histologically as typical of fibrolamellar carcinoma, 12 cases as 'possible fibrolamellar carcinoma' and 8 cases as 'unlikely to be fibrolamellar carcinoma'. PRKACA FISH was positive for rearrangement in 102 of 103 (99%) typical fibrolamellar carcinomas, 9 of 12 'possible fibrolamellar carcinomas' and 0 of 8 cases 'unlikely to be fibrolamellar carcinomas'. Within the morphologically typical group of fibrolamellar carcinomas, two tumors with unusual FISH patterns were also identified. Both cases had the fusion gene DNAJB1-PRKACA, but one also had amplification of the fusion gene and one had heterozygous deletion of the normal PRKACA locus. In addition, 88 conventional hepatocellular carcinomas were evaluated with PRKACA FISH and all were negative. These findings demonstrate that FISH for the PRKACA rearrangement is a clinically useful tool to confirm the diagnosis of fibrolamellar carcinoma, with high sensitivity and specificity. A diagnosis of fibrolamellar carcinoma is more accurate when based on morphology plus confirmatory testing than when based on morphology alone

KELT-3b: A Hot Jupiter Transiting a V=9.8 Late-F Star

We report the discovery of KELT-3b, a moderately inflated transiting hot Jupiter with a mass of 1.477 (-0.067, +0.066) M_J, and radius of 1.345 +/- 0.072 R_J, with an orbital period of 2.7033904 +/- 0.000010 days. The host star, KELT-3, is a V=9.8 late F star with M_* = 1.278 (-0.061, +0.063) M_sun, R_* = 1.472 (-0.067, +0.065) R_sun, T_eff = 6306 (-49, +50) K, log(g) = 4.209 (-0.031, +0.033), and [Fe/H] = 0.044 (-0.082, +0.080), and has a likely proper motion companion. KELT-3b is the third transiting exoplanet discovered by the KELT survey, and is orbiting one of the 20 brightest known transiting planet host stars, making it a promising candidate for detailed characterization studies. Although we infer that KELT-3 is significantly evolved, a preliminary analysis of the stellar and orbital evolution of the system suggests that the planet has likely always received a level of incident flux above the empirically-identified threshold for radius inflation suggested by Demory & Seager (2011).Comment: 12 pages, 12 figures, accepted to Ap

Quantifying the CDK inhibitor VMY-1-103\u27s activity and tissue levels in an in vivo tumor model by LC-MS/MS and by MRI.

The development of new small molecule-based therapeutic drugs requires accurate quantification of drug bioavailability, biological activity and treatment efficacy. Rapidly measuring these endpoints is often hampered by the lack of efficient assay platforms with high sensitivity and specificity. Using an in vivo model system, we report a simple and sensitive liquid chromatography-tandem mass spectrometry assay to quantify the bioavailability of a recently developed novel cyclin-dependent kinase inhibitor VMY-1-103, a purvalanol B-based analog whose biological activity is enhanced via dansylation. We developed a rapid organic phase extraction technique and validated wide and functional VMY-1-103 distribution in various mouse tissues, consistent with its enhanced potency previously observed in a variety of human cancer cell lines. More importantly, in vivo MRI and single voxel proton MR-Spectroscopy further established that VMY-1-103 inhibited disease progression and affected key metabolites in a mouse model of hedgehog-driven medulloblastoma