Aims. Substance‐abusing populations perform poorly on decision‐making tasks related to delay and risk. These tasks include: (1) the Delay Discounting Procedure (DDP), in which choices are made ...between smaller‐sooner and later‐larger rewards, (2) the Gambling Task (GT), in which choices are made between alternatives varying in pay‐off and punishment, and (3) the Rogers Decision‐Making Task (RDMT) in which subjects choose between higher or lower probability gambles. We examine the interrelationship among these tasks.
Design. A test battery was created which included the DDP, GT and RDMT, as well as measures of impulsivity, intellectual functioning and drug use.
Setting. Subjects completed the test battery at an outpatient center, prior to beginning 12 weeks of treatment.
Participants. Thirty‐two treatment‐seeking cocaine dependent individuals (primarily African‐American males) participated.
Findings. Performance on the GT was significantly correlated with performance on the DDP (
r = 0.37;
p = 0.04). Reaction times on the RDMT correlated with performance on the GT (
r = 0.36,
p = 0.04) and DDP (
r = 0.33,
p = 0.07), but actual choices on the RDMT did not (
p > 0.9 for both). While no significant relationships were observed between task performance and impulsivity, IQ estimate was positively correlated with both the GT (
r = 0.44,
p = 0.01) and RDMT (
r = 0.41,
p = 0.021). Split half reliability data indicated higher reliability when using only data from the latter half of the GT (
r = 0.92 vs.
r = 0.80).
Conclusions. These data offer preliminary evidence of overlap in the decision‐making functioning tapped by these tasks. Possible implications for drug‐taking behavior are discussed.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The electronic structures of CdSe/CdTe type II colloidal quantum dots are predicted using a model based on k·p theory and the many-particle configuration interaction method. The separation of energy ...levels in the conduction band is examined and used to identify phonon bottlenecks, and how these evolve as the shell thickness is increased. Bottlenecks are found to persist both above and below the threshold for multiple exciton generation for all the shell thicknesses investigated. The overall electron cooling rate is thus expected to fall as the shell thickness is increased and Auger cooling suppressed, and this is confirmed experimentally using ultrafast transient absorption measurements. A reduced overall rate of electron cooling will enhance the quantum yield of multiple exciton generation with which it competes. Using a detailed-balance model, we have thus calculated that with proper design of core/and shell structures the efficiency of a solar cell based on CdSe/CdTe quantum dots can be enhanced to 36.5% by multiple exciton generation.
•The energy structure of CdSe/CdTe core/shell colloidal QD is calculated using CI theory.•It is found that phonon bottlenecks remain above the threshold for MEG.•Phonon cooling is not significant as the shell thickness is increased.•This predicted reduction of electron cooling is confirmed experimentally.•The impact on solar cell performance of the MEG QY is assessed using a detail balance model.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Genomic analysis of multi-focal renal cell carcinomas from an individual with a germline VHL mutation offers a unique opportunity to study tumor evolution.
We perform whole exome sequencing on four ...clear cell renal cell carcinomas removed from both kidneys of a patient with a germline VHL mutation. We report that tumors arising in this context are clonally independent and harbour distinct secondary events exemplified by loss of chromosome 3p, despite an identical genetic background and tissue microenvironment. We propose that divergent mutational and copy number anomalies are contingent upon the nature of 3p loss of heterozygosity occurring early in tumorigenesis. However, despite distinct 3p events, genomic, proteomic and immunohistochemical analyses reveal evidence for convergence upon the PI3K-AKT-mTOR signaling pathway. Four germline tumors in this young patient, and in a second, older patient with VHL syndrome demonstrate minimal intra-tumor heterogeneity and mutational burden, and evaluable tumors appear to follow a linear evolutionary route, compared to tumors from patients with sporadic clear cell renal cell carcinoma.
In tumors developing from a germline VHL mutation, the evolutionary principles of contingency and convergence in tumor development are complementary. In this small set of patients with early stage VHL-associated tumors, there is reduced mutation burden and limited evidence of intra-tumor heterogeneity.
Twin, family and adoption studies have suggested that vulnerability to opioid dependence may be a partially inherited trait (Cadoret et al., 1986; Merikangas et al., 1998; Tsuang et al., 1998, 2001). ...Studies using animal models also support a role for genetic factors in opioid dependence, and point to a locus of major effect on mouse chromosome 10 (Berrettini et al., 1994; Alexander et al., 1996), which harbors the mu opioid receptor gene (Mor1) (Kozak et al., 1994). The gene encoding the human mu opioid receptor (OPRM1) is thus an obvious candidate gene for contributing to opioid dependence. A recent report (Hoehe et al., 2000) found a significant association between a specific combination of OPRM1 single nucleotide polymorphisms (SNPs) and substance dependence.
In the current study, we genotyped 213 subjects with severe opioid dependence (89 African-Americans, 124 European-Americans) and 196 carefully screened "supercontrol" subjects (96 African-Americans, 100 European-Americans) at five SNPs residing in the OPRM1 gene. The polymorphisms include three in the promoter region (T-1793A, -1699T insertion and A-1320G) and two in exon 1 (C+17T Ala6Val and A+118G Asp40Asn).
Statistical analysis of the allele frequency differences between opioid-dependent and control subjects for each of the polymorphisms studied yielded P values in the range of 0.444-1.000. Haplotype analysis failed to identify any specific combination of SNPs associated with the phenotype.
Despite reasonable statistical power we found no evidence of association between the five mu opioid receptor polymorphisms studied and severe opioid dependence in our sample. There were, however, significant allele frequency differences between African-Americans and European-Americans for all five polymorphisms, irrespective of drug-dependent status. Linkage disequilibrium analysis of the African-American genotypes indicated linkage disequilibrium (P<0.0001) across the five-polymorphism, 1911 base pair region. In addition, only four haplotypes of these five polymorphisms are predicted to exist in African-Americans.
Individuals must feel free to exert personal control over decisions regarding research participation. We present an examination of participants' perceived personal control over, as well as reported ...pressures and threats from others, influencing their decision to join a study assessing the effectiveness of extended-release naltrexone in preventing opioid dependence relapse. Most participants endorsed a strong sense of control over the decision; few reported pressures or threats. Although few in number, participants' brief narrative descriptions of the pressures and threats are illuminating and provide context for their perceptions of personal control. Based on this work, we propose a useful set of tools to help ascertain participants' sense of personal control in joining research.
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BFBNIB, NMLJ, NUK, OILJ, PNG, SAZU, UKNU, UL, UM, UPUK, ZRSKP
To examine whether the addition of counseling, medical care, and psychosocial services improves the efficacy of methadone hydrochloride therapy in the rehabilitation of opiate-dependent patients.
...Random assignment to one of three treatment groups for a 6-month clinical trial: (1) minimum methadone services (MMS)--methadone alone (a minimum of 60 mg/d) with no other services; (2) standard methadone services (SMS)--same dose of methadone plus counseling; or (3) enhanced methadone services (EMS)--same dose of methadone plus counseling and on-site medical/psychiatric, employment, and family therapy.
The methadone maintenance program of the Philadelphia (Pa) Veterans Affairs Medical Center.
Ninety-two male intravenous opiate users in methadone maintenance treatment.
While methadone treatment alone (MMS) was associated with reductions in opiate use, 69% of these subjects had to be "protectively transferred" from the trial because of unremitting use of opiates or cocaine, or medical/psychiatric emergencies. This was significantly different from the 41% of SMS subjects and 19% of EMS subjects who met the criteria. End-of-treatment data (at 24 weeks) showed minimal improvements among the 10 MMS patients who completed the trial. The SMS group showed significantly more and larger improvements than did the MMS group; and the EMS group showed significantly better outcomes than did the SMS group. Minimum methadone services subjects who had been "protectively transferred" to standard care showed significant reductions in opiate and cocaine use within 4 weeks.
Methadone alone (even in substantial doses) may only be effective for a minority of eligible patients. The addition of basic counseling was associated with major increases in efficacy; and the addition of on-site professional services was even more effective.
Local Adaptation in Community Perception O’Brien, Daniel Tumminelli; Norton, Charles Cornell; Cohen, Jeremy ...
Environment and behavior,
02/2014, Volume:
46, Issue:
2
Journal Article
Peer reviewed
When observing an unfamiliar neighborhood, people use indicators of physical disorder to judge the local community (i.e., community perception), associating them with crime and weak relationships ...between neighbors. The authors argue that these judgments depend on people’s definition of disorder, which is adapted to their local community. This is tested with an experiment. Undergraduate students from across New York State rated the collective efficacy (i.e., social quality) of neighborhoods from a single city using images of physical structures. Participants reported which features they attended to when making these judgments. Participants were categorized as being from New York City (NYC), NYC suburbs, or the less densely populated upstate region. Images were from an upstate city. Those from NYC attended more to pavement than others. Ratings by those from upstate were most accurate and positive. These results supported the initial hypotheses and suggested that community perception combines heuristics and familiarity to make inferences.
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Bevacizumab (BEV) is commonly used for treating recurrent glioblastoma (GBM), and wound healing is a well-established adverse event. Retrospective analysis of GBM patients with and without wound ...healing complications while on BEV treatment is reported. 287 patients identified, majority were males (60 %) with median age of 52.5 years. 14 cases identified with wound healing problems, related to either craniotomy (n = 8) or other soft tissue wounds (n = 6). Median duration of BEV treatment to complication was 62 days (range 6–559). Majority received 10 mg/kg (n = 11) and nine (64.3 %) were on corticosteroids, with median daily dose of 6 mg (range 1–16 mg) for median of 473 days before starting BEV. For dehisced craniotomy wounds, median time for starting BEV from last surgery was 29 days (range 27–345). Median time from starting BEV to developing wound complication was 47 days (range 16–173). Seven (87.5 %) had infected wounds requiring antibiotics, hospitalization. Four (50 %) required plastic surgery. BEV stopped and safely resumed in 6 (75 %) patients; median delay was 70 days (range 34–346). Soft tissue wounds included decubitus ulcer, dehisced striae, herpes simplex, trauma to hand and back, and abscess. Median time from starting BEV to wound issues was 72 days (range 6–559). Five (83.3 %) were infected, requiring antibiotics. While three (50 %) required hospitalization, none required plastic surgery. Treatment stopped in five (83.3 %) and restarted in two (median delay 48 days, range 26–69). Wound healing complications are uncommon but associated with significant morbidity. Identifying those at risk and contributing factors warrants further investigation.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Assessing and mitigating the abuse liability (AL) of analgesics is an urgent clinical and societal problem. Recommendations for improved assessment include: (1) performing trials that include ...individuals with diverse risks of abuse; (2) improving the assessment of AL in clinical trials (eg, training study personnel in the principles of abuse and addiction behaviors, designing the trial to assess AL outcomes as primary or secondary outcome measures depending on the trial objectives); (3) performing standardized assessment of outcomes, including targeted observations by study personnel and using structured adverse events query forms that ask all subjects specifically for certain symptoms (such as euphoria and craving); and (4) collecting detailed information about events of potential concern (eg, unexpected urine drug testing results, loss of study medication, and dropping out the trial).
Assessing and mitigating the abuse liability (AL) of analgesics is an urgent clinical and societal problem. Analgesics have traditionally been assessed in randomized clinical trials (RCTs) designed to demonstrate analgesic efficacy relative to placebo or an active comparator. In these trials, rigorous, prospectively designed assessment for AL is generally not performed. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) convened a consensus meeting to review the available evidence and discuss methods for improving the assessment of the AL of analgesics in clinical trials in patients with pain. Recommendations for improved assessment include: (1) performing trials that include individuals with diverse risks of abuse; (2) improving the assessment of AL in clinical trials (eg, training study personnel in the principles of abuse and addiction behaviors, designing the trial to assess AL outcomes as primary or secondary outcome measures depending on the trial objectives); (3) performing standardized assessment of outcomes, including targeted observations by study personnel and using structured adverse events query forms that ask all subjects specifically for certain symptoms (such as euphoria and craving); and (4) collecting detailed information about events of potential concern (eg, unexpected urine drug testing results, loss of study medication, and dropping out of the trial). The authors also propose a research agenda for improving the assessment of AL in future trials.
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GEOZS, IJS, IMTLJ, KILJ, OILJ, SBJE, UL, UPUK
We recommend that four subjective effects measures should be included in ALA studies of opioid analgesics: drug liking, likelihood to take again, drug identification, and drug high. These can be ...considered core primary outcome measures, that is, core in the sense that these measures should be part of any opioid ALA battery, and primary in the sense that they are important measures in determining the AL of a drug.
A critical component in development of opioid analgesics is assessment of their abuse liability (AL). Standardization of approaches and measures used in assessing AL have the potential to facilitate comparisons across studies, research laboratories, and drugs. The goal of this report is to provide consensus recommendations regarding core outcome measures for assessing the abuse potential of opioid medications in humans in a controlled laboratory setting. Although many of the recommended measures are appropriate for assessing the AL of medications from other drug classes, the focus here is on opioid medications because they present unique risks from both physiological (e.g., respiratory depression, physical dependence) and public health (e.g., individuals in pain) perspectives. A brief historical perspective on AL testing is provided, and those measures that can be considered primary and secondary outcomes and possible additional outcomes in AL assessment are then discussed. These outcome measures include the following: subjective effects (some of which comprise the primary outcome measures, including drug liking; physiological responses; drug self-administration behavior; and cognitive and psychomotor performance. Before presenting recommendations for standardized approaches and measures to be used in AL assessments, the appropriateness of using these measures in clinical trials with patients in pain is discussed.
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