Paradoxical effects of shock: The role of shock intensity and interresponse times followed by shock

In operant conditioning experiments concerned with punishment, when electric shock is contingent on an animal\u27s response, response rates typically decrease. In some cases, however, response rates increase. Four experiments investigated these paradoxical effects of shock by manipulating shock intensity and the time between two consecutive responses (interresponse time) that produces shock. Lever pressing by rats was maintained by a variable-interval 40-s schedule of food reinforcement. Shock followed either relatively long (Experiments 1 and 2) or relatively short (Experiments 3 and 4) interresponse times. The range of interresponse times eligible for shock was raised by lowering or raising the interresponse times that produced shock. Shock intensity was raised from 0.05 mA to either 0.4 mA or 0.8mA. Shock contingent on long interresponse times punished long interresponse times, leading to increased response rates. Shock contingent on short interresponse times punished short interresponse times, leading to decreased response rates. In two experiments, raising the range of interresponse times that produced shock increased or decreased response rates depending on whether the interresponse times were long or short, respectively. In the other two experiments, there was an effect of shock intensity. When long interresponse times produced shock, low intensities punished long interresponse times and increased response rates. High intensities had the opposite effect. When short interresponse times produced shock, high shock intensities punished short interresponse times and decreased response rates more than low intensities. These results demonstrate that interresponse times may serve as functional units of behavior when the behavioral consequence is a punisher and may explain why punishment procedures occasionally increase responding. Moreover, they establish experimental parameters that may be useful for future studies of punishment

The behavioral functions of stimuli signaling transitions across rich and lean schedules of reinforcement

The present experiment was designed to assess whether stimuli correlated with rich and lean fixed-ratio schedule components would function as conditioned reinforcers and conditioned punishers, respectively. Pigeons responded on a mixed schedule with fixed-ratio components leading to large or small food reinforcers. Pecks on either of two observing keys converted the mixed schedule to a multiple schedule by turning on a color associated with the current component. The stimulus consequences of the observing responses were manipulated across conditions. Pecks on one observing key produced the rich stimulus and the lean stimulus whereas pecks on the other observing key produced only the rich or the lean stimulus. The stimulus correlated with the large reinforcer functioned as a conditioned reinforcer---it maintained observing behavior---whereas the stimulus correlated with the small reinforcer did not. There was no evidence that the stimulus correlated with the small reinforcer functioned as a conditioned punisher

Incidence of Heart Failure or Cardiomyopathy After Adjuvant Trastuzumab Therapy for Breast Cancer

ObjectivesThe purpose of this study was to estimate heart failure (HF) and cardiomyopathy (CM) rates after adjuvant trastuzumab therapy and chemotherapy in a population of older women with early-stage breast cancer.BackgroundNewer biologic therapies for breast cancer such as trastuzumab have been reported to increase HF and CM in clinical trials, especially in combination with anthracycline chemotherapy. Elderly patients, however, typically have a higher prevalence of cardiovascular risk factors and have been underrepresented in trastuzumab clinical trials.MethodsUsing Surveillance, Epidemiology, and End Results-Medicare data from 2000 through 2007, we identified women 67 to 94 years of age with early-stage breast cancer. We calculated 3-year incidence rates of HF or CM for the following mutually exclusive treatment groups: trastuzumab (with or without nonanthracycline chemotherapy), anthracycline plus trastuzumab, anthracycline (without trastuzumab and with or without nonanthracycline chemotherapy), other nonanthracycline chemotherapy, or no adjuvant chemotherapy or trastuzumab therapy. HF or CM events were ascertained from administrative Medicare claims. Poisson regression was used to quantify risk of HF or CM, adjusting for sociodemographic factors, cancer characteristics, and cardiovascular conditions.ResultsWe identified 45,537 older women (mean age: 76.2 years, standard deviation: 6.2 years) with early-stage breast cancer. Adjusted 3-year HF or CM incidence rates were higher for patients receiving trastuzumab (32.1 per 100 patients) and anthracycline plus trastuzumab (41.9 per 100 patients) compared with no adjuvant therapy (18.1 per 100 patients, p < 0.001). Adding trastuzumab to anthracycline therapy added 12.1, 17.9, and 21.7 HF or CM events per 100 patients over 1, 2, and 3 years of follow-up, respectively.ConclusionsHF or CM are common complications after trastuzumab therapy for older women, with higher rates than those reported from clinical trials

An oncocytic adrenal tumour in a patient with Birt‐Hogg‐Dubé syndrome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106917/1/cen12292.pd

Barriers to Pediatricians’ Adherence to American Academy of Pediatrics Oral Health Referral Guidelines: North Carolina General Dentists’ Opinions

Purpose—The purposes of this study were to: (1) assess knowledge, attitudes, and behaviors of North Carolina general dentists (GDs) regarding American Academy of Pediatrics (AAP) dental referral guidelines; and (2) determine factors that influence pediatricians’ ability to comply with AAP guidelines. Methods—One thousand GDs were surveyed to determine barriers toward acceptance of physician referrals of infants and toddlers. The primary outcome using ordered logistic regression was GDs’ acceptance of children described in five case scenarios, with different levels of risk and oral health status. Results—GDs believed pediatricians should refer patients at risk for caries to a dentist. While 61 to 75 percent of GDs were willing to accept low caries risk referrals of infants and toddlers, only 35 percent would accept referrals when caries was present. Predictors of referral acceptance were correct knowledge about AAP guidelines (OR=2.0, 95%CI=1.2-3.3), confidence in pro- viding preventive care to infants and toddlers (OR=2.6, 95%CI=1.3-4.9), and agreement that parents see importance in dental referrals (OR=2.1, 95% CI=1.2-3.6). Conclusions—This study identified factors influencing acceptance of pediatrician referrals for the age one dental visit among North Carolina GDs and highlighted challenges pediatricians face in referring young children for dental care

Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.We sequenced the genomes of 3,615 strains of serotype Emm protein 1 (M1) group A Streptococcus to unravel the nature and timing of molecular events contributing to the emergence, dissemination, and genetic diversification of an unusually virulent clone that now causes epidemic human infections worldwide. We discovered that the contemporary epidemic clone emerged in stepwise fashion from a precursor cell that first contained the phage encoding an extracellular DNase virulence factor (streptococcal DNase D2, SdaD2) and subsequently acquired the phage encoding the SpeA1 variant of the streptococcal pyrogenic exotoxin A superantigen. The SpeA2 toxin variant evolved from SpeA1 by a single-nucleotide change in the M1 progenitor strain before acquisition by horizontal gene transfer of a large chromosomal region encoding secreted toxins NAD(+)-glycohydrolase and streptolysin O. Acquisition of this 36-kb region in the early 1980s into just one cell containing the phage-encoded sdaD2 and speA2 genes was the final major molecular event preceding the emergence and rapid intercontinental spread of the contemporary epidemic clone. Thus, we resolve a decades-old controversy about the type and sequence of genomic alterations that produced this explosive epidemic. Analysis of comprehensive, population-based contemporary invasive strains from seven countries identified strong patterns of temporal population structure. Compared with a preepidemic reference strain, the contemporary clone is significantly more virulent in nonhuman primate models of pharyngitis and necrotizing fasciitis. A key finding is that the molecular evolutionary events transpiring in just one bacterial cell ultimately have produced millions of human infections worldwide.Knut and Alice Wallenberg Foundation Swedish Research Council Houston Methodist Hospital Fondren Foundatio

An oligotrophic deep-subsurface community dependent on syntrophy is dominated by sulfur-driven autotrophic denitrifiers

Subsurface lithoautotrophic microbial ecosystems (SLiMEs) under oligotrophic conditions are typically supported by H₂. Methanogens and sulfate reducers, and the respective energy processes, are thought to be the dominant players and have been the research foci. Recent investigations showed that, in some deep, fluid-filled fractures in the Witwatersrand Basin, South Africa, methanogens contribute <5% of the total DNA and appear to produce sufficient CH₄ to support the rest of the diverse community. This paradoxical situation reflects our lack of knowledge about the in situ metabolic diversity and the overall ecological trophic structure of SLiMEs. Here, we show the active metabolic processes and interactions in one of these communities by combining metatranscriptomic assemblies, metaproteomic and stable isotopic data, and thermodynamic modeling. Dominating the active community are four autotrophic β-proteobacterial genera that are capable of oxidizing sulfur by denitrification, a process that was previously unnoticed in the deep subsurface. They co-occur with sulfate reducers, anaerobic methane oxidizers, and methanogens, which each comprise <5% of the total community. Syntrophic interactions between these microbial groups remove thermodynamic bottlenecks and enable diverse metabolic reactions to occur under the oligotrophic conditions that dominate in the subsurface. The dominance of sulfur oxidizers is explained by the availability of electron donors and acceptors to these microorganisms and the ability of sulfur-oxidizing denitrifiers to gain energy through concomitant S and H₂ oxidation. We demonstrate that SLiMEs support taxonomically and metabolically diverse microorganisms, which, through developing syntrophic partnerships, overcome thermodynamic barriers imposed by the environmental conditions in the deep subsurface