The most commonly cited descriptions of the behavioral characteristics of habituation come from two papers published almost 40 years ago Groves, P. M., & Thompson, R. F. (1970). Habituation: A ...dual-process theory.
Psychological Review,
77, 419–450; Thompson, R. F., & Spencer, W. A. (1966). Habituation: A model phenomenon for the study of neuronal substrates of behavior.
Psychological Review,
73, 16–43. In August 2007, the authors of this review, who study habituation in a wide range of species and paradigms, met to discuss their work on habituation and to revisit and refine the characteristics of habituation. This review offers a re-evaluation of the characteristics of habituation in light of these discussions. We made substantial changes to only a few of the characteristics, usually to add new information and expand upon the description rather than to substantially alter the original point. One additional characteristic, relating to long-term habituation, was added. This article thus provides a modern summary of the characteristics defining habituation, and can serve as a convenient primer for those whose research involves stimulus repetition.
People with diabetes can suffer from diverse complications that seriously erode quality of life. Diabetes, costing the United States more than $174 billion per year in 2007, is expected to take an ...increasingly large financial toll in subsequent years. Accurate projections of diabetes burden are essential to policymakers planning for future health care needs and costs.
Using data on prediabetes and diabetes prevalence in the United States, forecasted incidence, and current US Census projections of mortality and migration, the authors constructed a series of dynamic models employing systems of difference equations to project the future burden of diabetes among US adults. A three-state model partitions the US population into no diabetes, undiagnosed diabetes, and diagnosed diabetes. A four-state model divides the state of "no diabetes" into high-risk (prediabetes) and low-risk (normal glucose) states. A five-state model incorporates an intervention designed to prevent or delay diabetes in adults at high risk.
The authors project that annual diagnosed diabetes incidence (new cases) will increase from about 8 cases per 1,000 in 2008 to about 15 in 2050. Assuming low incidence and relatively high diabetes mortality, total diabetes prevalence (diagnosed and undiagnosed cases) is projected to increase from 14% in 2010 to 21% of the US adult population by 2050. However, if recent increases in diabetes incidence continue and diabetes mortality is relatively low, prevalence will increase to 33% by 2050. A middle-ground scenario projects a prevalence of 25% to 28% by 2050. Intervention can reduce, but not eliminate, increases in diabetes prevalence.
These projected increases are largely attributable to the aging of the US population, increasing numbers of members of higher-risk minority groups in the population, and people with diabetes living longer. Effective strategies will need to be undertaken to moderate the impact of these factors on national diabetes burden. Our analysis suggests that widespread implementation of reasonably effective preventive interventions focused on high-risk subgroups of the population can considerably reduce, but not eliminate, future increases in diabetes prevalence.
Summary A vast range of disorders—from indolent to fast-growing lesions—are labelled as cancer. Therefore, we believe that several changes should be made to the approach to cancer screening and care, ...such as use of new terminology for indolent and precancerous disorders. We propose the term indolent lesion of epithelial origin, or IDLE, for those lesions (currently labelled as cancers) and their precursors that are unlikely to cause harm if they are left untreated. Furthermore, precursors of cancer or high-risk disorders should not have the term cancer in them. The rationale for this change in approach is that indolent lesions with low malignant potential are common, and screening brings indolent lesions and their precursors to clinical attention, which leads to overdiagnosis and, if unrecognised, possible overtreatment. To minimise that potential, new strategies should be adopted to better define and manage IDLEs. Screening guidelines should be revised to lower the chance of detection of minimal-risk IDLEs and inconsequential cancers with the same energy traditionally used to increase the sensitivity of screening tests. Changing the terminology for some of the lesions currently referred to as cancer will allow physicians to shift medicolegal notions and perceived risk to reflect the evolving understanding of biology, be more judicious about when a biopsy should be done, and organise studies and registries that offer observation or less invasive approaches for indolent disease. Emphasis on avoidance of harm while assuring benefit will improve screening and treatment of patients and will be equally effective in the prevention of death from cancer.
I am pleased to submit a viewpoint titled “Body mass index on perinatal depression: A critical viewpoint” in response to an article by Ventriglio et al. titled, “The impact of body mass index on the ...pregnancy outcomes and risk of perinatal depression: Findings from a multicenter Italian study” for consideration for publication in your journal.
Despite recent advances in analytical and computational chemistry, lipid identification remains a significant challenge in lipidomics. Ion-mobility spectrometry provides an accurate measure of the ...molecules’ rotationally averaged collision cross-section (CCS) in the gas phase and is thus related to ionic shape. Here, we investigate the use of CCS as a highly specific molecular descriptor for identifying lipids in biological samples. Using traveling wave ion mobility mass spectrometry (MS), we measured the CCS values of over 200 lipids within multiple chemical classes. CCS values derived from ion mobility were not affected by instrument settings or chromatographic conditions, and they were highly reproducible on instruments located in independent laboratories (interlaboratory RSD < 3% for 98% of molecules). CCS values were used as additional molecular descriptors to identify brain lipids using a variety of traditional lipidomic approaches. The addition of CCS improved the reproducibility of analysis in a liquid chromatography-MS workflow and maximized the separation of isobaric species and the signal-to-noise ratio in direct-MS analyses (e.g., “shotgun” lipidomics and MS imaging). These results indicate that adding CCS to databases and lipidomics workflows increases the specificity and selectivity of analysis, thus improving the confidence in lipid identification compared to traditional analytical approaches. The CCS/accurate-mass database described here is made publicly available.
Objective To determine safety and pharmacodynamics/efficacy of teduglutide in children with intestinal failure associated with short bowel syndrome (SBS-IF). Study design This 12-week, open-label ...study enrolled patients aged 1-17 years with SBS-IF who required parenteral nutrition (PN) and showed minimal or no advance in enteral nutrition (EN) feeds. Patients enrolled sequentially into 3 teduglutide cohorts (0.0125 mg/kg/d n = 8, 0.025 mg/kg/d n = 14, 0.05 mg/kg/d n = 15) or received standard of care (SOC, n = 5). Descriptive summary statistics were used. Results All patients experienced ≥1 treatment-emergent adverse event; most were mild or moderate. No serious teduglutide-related treatment-emergent adverse events occurred. Between baseline and week 12, prescribed PN volume and calories (kcal/kg/d) changed by a median of −41% and −45%, respectively, with 0.025 mg/kg/d teduglutide and by −25% and −52% with 0.05 mg/kg/d teduglutide. In contrast, PN volume and calories changed by 0% and −6%, respectively, with 0.0125 mg/kg/d teduglutide and by 0% and −1% with SOC. Per patient diary data, EN volume increased by a median of 22%, 32%, and 40% in the 0.0125, 0.025, and 0.05 mg/kg/d cohorts, respectively, and by 11% with SOC. Four patients achieved independence from PN, 3 in the 0.05 mg/kg/d cohort and 1 in the 0.025 mg/kg/d cohort. Study limitations included its short-term, open-label design, and small sample size. Conclusions Teduglutide was well tolerated in pediatric patients with SBS-IF. Teduglutide 0.025 or 0.05 mg/kg/d was associated with trends toward reductions in PN requirements and advancements in EN feeding in children with SBS-IF. Trial registration ClinicalTrials.gov: NCT01952080 ; EudraCT: 2013-004588-30.
Increasing evidence suggests that asthma is a heterogeneous disorder regulated by distinct molecular mechanisms. In a cross-sectional study of asthmatics of varying severity (n = 51), endobronchial ...tissue gene expression analysis revealed three major patient clusters: TH2-high, TH17-high, and TH2/17-low. TH2-high and TH17-high patterns were mutually exclusive in individual patient samples, and their gene signatures were inversely correlated and differentially regulated by interleukin-13 (IL-13) and IL-17A. To understand this dichotomous pattern of T helper 2 (TH2) and TH17 signatures, we investigated the potential of type 2 cytokine suppression in promoting TH17 responses in a preclinical model of allergen-induced asthma. Neutralization of IL-4 and/or IL-13 resulted in increased TH17 cells and neutrophilic inflammation in the lung. However, neutralization of IL-13 and IL-17 protected mice from eosinophilia, mucus hyperplasia, and airway hyperreactivity and abolished the neutrophilic inflammation, suggesting that combination therapies targeting both pathways may maximize therapeutic efficacy across a patient population comprising both TH2 and TH17 endotypes.
Purpose To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) ...therapy. Methods A multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline. Guideline development involved a systematic review of the literature and an informal consensus process. The systematic review focused on guidelines, systematic reviews and meta-analyses, randomized controlled trials, and case series published from 2000 through 2017. Results The systematic review identified 204 eligible publications. Much of the evidence consisted of systematic reviews of observational data, consensus guidelines, case series, and case reports. Due to the paucity of high-quality evidence on management of immune-related adverse events, recommendations are based on expert consensus. Recommendations Recommendations for specific organ system-based toxicity diagnosis and management are presented. While management varies according to organ system affected, in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, with the exception of some neurologic, hematologic, and cardiac toxicities. ICPi therapy may be suspended for most grade 2 toxicities, with consideration of resuming when symptoms revert to grade 1 or less. Corticosteroids may be administered. Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids (prednisone 1 to 2 mg/kg/d or methylprednisolone 1 to 2 mg/kg/d). Corticosteroids should be tapered over the course of at least 4 to 6 weeks. Some refractory cases may require infliximab or other immunosuppressive therapy. In general, permanent discontinuation of ICPis is recommended with grade 4 toxicities, with the exception of endocrinopathies that have been controlled by hormone replacement. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .
Objective: Childhood abuse and other adverse childhood experiences (ACEs) have historically been studied individually, and relatively little is known about the co-occurrence of these events. The ...purpose of this study is to examine the degree to which ACEs co-occur as well as the nature of their co-occurrence.
Method: We used data from 8,629 adult members of a health plan who completed a survey about 10 ACEs which included: childhood abuse (emotional, physical, and sexual), neglect (emotional and physical), witnessing domestic violence, parental marital discord, and living with substance abusing, mentally ill, or criminal household members. The bivariate relationship between each of these 10 ACEs was assessed, and multivariate linear regression models were used to describe the interrelatedness of ACEs after adjusting for demographic factors.
Results: Two-thirds of participants reported at least one ACE; 81%–98% of respondents who had experienced one ACE reported at least one additional ACE (median: 87%). The presence of one ACE significantly increased the prevalence of having additional ACEs, elevating the adjusted odds by 2 to 17.7 times (median: 2.8). The observed number of respondents with high ACE scores was notably higher than the expected number under the assumption of independence of ACEs (
p < .0001), confirming the statistical interrelatedness of ACEs.
Conclusions: The study provides strong evidence that ACEs are interrelated rather than occurring independently. Therefore, collecting information about exposure to other ACEs is advisable for studies that focus on the consequences of a specific ACE. Assessment of multiple ACEs allows for the potential assessment of a graded relationship between these childhood exposures and health and social outcomes.
Objectif: De tradition, on a étudié les mauvais traitements et d’autres expériences nocives de l’enfance séparément, donc peu est connu des situations où les deux se produisent ensemble. Le but de cette étude fut d’examiner dans quelle mesure plusieurs expériences néfastes se produisent et quelle est la nature des liens qui les caractérisent.
Méthode: Notre étude s’est servie de données sur 8.629 adultes membres d’un plan de santé, lesquels ont répondu à une enquête concernant dix expériences affligeantes (comprenant la maltraitance physique, sexuelle et émotionnelle, la négligence physique et émotionnelle, le fait d’avoir été témoin de violence entre conjoints ou dans la famille, le fait d’être exposé à la discorde entre conjoints ou les problèmes de drogue ou d’alcool, la maladie mentale ou les activités criminelles de la part des membres de la famille). On a étudié la relation bi-variable entre chacune de ces expériences, puis on a eu recours à un modèle de régression linéaire à plusieurs variables pour expliquer les liens entre ces expériences, ayant d’abord pris en considération les facteurs démographiques.
Résultats: Les deux tiers des participants rapportent avoir vécu au moins une expérience nocive; entre 81% et 98% des participants de ce groupe ont aussi connu au moins une autre expérience malheureuse (médiane: 87%). D’avoir vécu une telle expérience prédispose clairement vers une ou plusieurs autres expériences, au point ou la probabilité s’élève de 2 à 17.7 fois (médiane: 2.8). Le nombre de participants ayant un score élevé est beaucoup plus considérable si l’on se fie à la probabilité (<.0001) que l’expérience serait un phénomène isolé, ce qui confirme qu’il existe véritablement une relation statistique entre ces expériences de vie.
Conclusions: L’étude apporte des preuves importantes à savoir que les expériences nocives en enfance sont reliées plutôt que d’être isolées les unes des autres. Donc, les études portant sur les conséquences d’une expérience nocive particulière devraient recueillir des données sur l’ensemble des expériences nocives que l’enfant a connues. Évaluer l’ensemble de ces expériences permettra de mieux dégager une gradation dans les relations entre ces diverses expériences d’une part, et les caractéristiques sanitaires et sociales.
Objetivo: El maltrato infantil y otras experiencias adversas de la infancia (EAIs) han sido estudiadas habitualmente de manera individual y se conoce relativamente poco sobre la co-ocurrencia de estos acontecimientos. El objetivo de este estudio es examinar el grado en que estas experiencias ocurren de manera simultánea y la naturaleza de dicha co-ocurrencia.
Método: Se utilizaron datos de 8629 miembros adultos de un plan de salud que completaron una encuesta sobre 10 experiencias adversas infantiles que incluı́an: maltrato infantil (emocional, fı́sico y sexual), negligencia (emocional y fı́sica), ser testigo de violencia doméstica, mala relación de pareja de los padres, haber vivido con una persona que abusa de drogas, con un enfermo mental o con delincuentes. Se evaluaron las relaciones bivariadas entre cada una de estas 10 experiencias adversas infantiles y se utilizaron modelos de regresión linear multivariada para describir las interrelaciones entre las experiencias adversas infantiles después de controlar los factores demográficos.
Resultados: Dos tercios de los participantes notificaron al menos una experiencia adversa infantil (EAI). Entre un 81% y un 98% de quienes experimentaron una EAI notificaron al menos una EAI adicional (mediana: 87%). La presencia de una EAI aumentó significativamente la prevalencia de haber tenido EAIs adicionales elevando las Odds ajustadas entre 2 y 17 veces (mediana: 2.8). El número observado de sujetos con altas puntuaciones en EAI era notablemente más alto que el número esperado bajo la asunción de independencia de EAIs. (
p < .0001) confirmando la interrelación estadı́stica de las EAIs.
Conclusiones: El estudio proporciona fuerte evidencia de que las EAIs están interrelacionadas y de que no ocurren de manera independiente. Además, se considera que recoger información sobre la exposición a otras EAIs es aconsejable para los estudios que se centran en las consecuencias de una EAI especı́fica. La evaluación de múltiples EAIs conduce a la evaluación potencial de una mayor relación entre estas experiencias infantiles y consecuencias sociales y sanitarias.
Pembrolizumab monotherapy, ipilimumab monotherapy, and pegylated interferon alfa-2b (PEG-IFN) monotherapy are active against melanoma and renal cell carcinoma (RCC). We explored the safety and ...preliminary antitumor activity of pembrolizumab combined with either ipilimumab or PEG-IFN in patients with advanced melanoma or RCC.
The phase Ib KEYNOTE-029 study (ClinicalTrials.gov, NCT02089685) included independent pembrolizumab plus reduced-dose ipilimumab and pembrolizumab plus PEG-IFN cohorts. Pembrolizumab 2 mg/kg every 3 weeks (Q3W) plus 4 doses of ipilimumab 1 mg/kg Q3W was tolerable if ≤6 of 18 patients experienced a dose-limiting toxicity (DLT). The target DLT rate for pembrolizumab 2 mg/kg Q3W plus PEG-IFN was 30%, with a maximum of 14 patients per dose level. Response was assessed per RECIST v1.1 by central review.
The ipilimumab cohort enrolled 22 patients, including 19 evaluable for DLTs. Six patients experienced ≥1 DLT. Grade 3 to 4 treatment-related adverse events occurred in 13 (59%) patients. Responses occurred in 5 of 12 (42%) patients with melanoma and 3 of 10 (30%) patients with RCC. In the PEG-IFN cohort, DLTs occurred in 2 of 14 (14%) patients treated at dose level 1 (PEG-IFN 1 μg/kg/week) and 2 of 3 (67%) patients treated at dose level 2 (PEG-IFN 2 μg/kg/week). Grade 3 to 4 treatment-related adverse events occurred in 10 of 17 (59%) patients. Responses occurred in 1 of 5 (20%) patients with melanoma and 2 of 12 (17%) patients with RCC.
Pembrolizumab 2 mg/kg Q3W plus ipilimumab 1 mg/kg Q3W was tolerable and provided promising antitumor activity in patients with advanced melanoma or RCC. The maximum tolerated dose of pembrolizumab plus PEG-IFN had limited antitumor activity in this population.
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