Variety Of Response Patterns Research Articles

Appearance of New Lesions Associate With Poor Prognosis in Pembrolizumab-Treated Urothelial Carcinoma

ObjectivesThis study investigated the variations in response patterns, including target lesion enlargement and the emergence of new lesions, in patients with urothelial carcinoma receiving pembrolizumab therapy and assessed the impact of new lesions on patient outcomes. MethodsThis retrospective analysis included patients with urothelial carcinoma treated with pembrolizumab following platinum failure. Response Evaluation Criteria in Solid Tumors criteria were used to assess the target lesion size and appearance of new lesions. Patients were categorized into 2 groups: the primary progressive disease (PD) group, consisting of patients who progressed within 28 to 84 days of treatment initiation, and the secondary PD group, consisting of patients who progressed more than 84 days after treatment initiation. Survival analyses were performed to evaluate the impact of new lesions on patient outcomes. ResultsIn this study, 42 patients experienced primary PD, and 37 experienced secondary PD. Among patients with primary PD, 64.3%, 73.8%, 45.2% had an increase of 20% or more in target lesion size, newly emerged lesions, and both an increase in target lesion size and new lesions, respectively. Kaplan–Meier analysis revealed that patients with primary PD and new lesions had significantly shorter overall survival after PD than those with only target lesion growth and those with secondary PD (both P < .001). ConclusionThis study revealed the heterogeneity of response patterns during pembrolizumab therapy in patients with urothelial carcinoma and primary pembrolizumab resistance and the presence of new lesions early in treatment. Earlier imaging evaluation should be performed to assess for the appearance of new lesions, leading to sequential treatment.

Modelling heat stress effects on milk production traits in Tunisian Holsteins using a random regression approach.

This study investigated the impact of temperature and humidity on milk production traits in Tunisian dairy cows, analysing population-level trends and individual cow responses using various modelling techniques and heat stress (HS) indices. Two distinct datasets were used for this purpose: the first included 551,139; 331,654 and 302,396 test-day records for milk, fat and protein yields, respectively. The second supplemented the production information with daily average (THIavg) and maximum (THImax) temperature-humidity index (THI) data. Three main parts of analyses were conducted simultaneously: classical least squares, identification of HS thresholds and associated production losses and assessment of individual cow responses using random regression models (RRM) fitting various continuous functions that include/exclude individual effects. The best model, determined by goodness-of-fit measurements, was a cubic polynomial function that accounted for individual variation and THIavg as a heat load measure. HS thresholds were established at THIavg/THImax of 70/74 for milk yield, 50/55 for fat percentage, 59/66 for protein percentage, 54/63 for fat yield and 56/66 for protein yield. According to the fitted polynomial models, daily milk production traits showed a curvilinear decline with accelerated loss rates beyond the established thermal thresholds. However, for all models and thermal indices, maximum daily production losses remained below 164 g/day, 4.4 g/day and 6.1 g/day for milk, fat and protein yields, respectively. Despite these losses, the relatively high thermal thresholds and lower associated production losses suggest that Tunisian dairy cows can tolerate high heat loads. Moreover, observed variations in response patterns indicate potential for selecting heat-tolerant individuals within this population.

Early FDG PET imaging and circulating T-cell repertoire biomarkers of response to chemotherapy and PD-1 checkpoint inhibitors in patients with stage IV NSCLC.

8622 Background: Chemotherapy and immune checkpoint inhibitors (chemoICI) for stage IV NSCLC without driver mutations produce variable response patterns and outcomes. Early assessment could establish selective benefit from treatment (de)escalation, consolidation, or adaptation. We evaluated FDG PET imaging and circulating T cell repertoire biomarkers of chemoICI response for clinical decision support. Methods: 35 patients with stage IV NSCLC prospectively enrolled on PET BRIGHT (NCT04151940) from 2019-2023 and received first-line carboplatin-pemetrexed-pembrolizumab. Synchronous FDG PET/CT and peripheral blood draws were performed prior to and after first dose of chemoICI at week 3. Imaging biomarkers included standardized uptake value (SUV) and total lesion glycolysis (TLG) metrics within the primary metabolic tumor volume and across lung lesions. Immunophenotyping included T cell receptor (TCR) sequencing from which TCR diversity metrics were extracted. Spearman correlation of FDG PET and TCR biomarkers with bi-dimensional size reduction after initial chemoICI was estimated. ROC analysis of PET and TCR biomarkers to discriminate chemoICI response status was benchmarked against PD-L1 testing, along with Mann-Whitney testing of groupwise differences. Results: The majority tested negative for PD-L1 (58% TPS&lt;1%). Most patients (63%) had partial response (PR) to initial chemoICI versus 33% with stable disease (SD) and 4% with progressive disease (PD). FDG PET primary tumor peak SUV decreased by a median of 15% [-82%, 63%] at week 3, while TLG decreased by 36% [-55%, 83%]. Higher baseline peak SUV and TLG, along with greater decline after first dose, were correlated with post-chemoICI size reduction (R 0.43-0.64, p=0.001-0.036). PR patients had higher baseline peak SUV (12 vs 6 g/mL, p=0.014) and greater week 3 decline in TLG (39% vs 7%, p=0.032) relative to SD/PD patients. Across lung lesions, PR-patient maximum SUV decreased while SD/PD-patient maximum SUV increased at week 3 (20% vs -19%, p=0.010). FDG PET biomarkers were stronger discriminators of chemoICI response status (AUC 0.75-0.82, p=0.009-0.046) than PD-L1 (AUC 0.60, p=0.42). Higher baseline blood TCR Simpson clonality was positively correlated with size reduction (R 0.70, p=0.004), whereas TCR Pielou evenness was negatively correlated (R -0.68, p=0.006). Higher baseline TCR clonality / lower TCR evenness discriminated chemoICI response status (AUC 0.80-0.84, p=0.028-0.049). TCR diversity changes were uncorrelated with response. Conclusions: FDG PET imaging prior to and after first dose chemoICI, along with baseline circulating T cell repertoire biomarkers, predict future response. Further investigation of these patient- and lesion-level biomarkers to guide personalized (de)escalation, consolidation, or adaptation of regimens for stage IV NSCLC is warranted. Clinical trial information: NCT04151940 .

Divergent experiences of Syrian refugee girls in Tripoli, Lebanon: a cross-sectional analysis to inform response and programming

BackgroundIn prior studies exploring the experiences of Syrian refugee girls in Tripoli, Beqaa, and Beirut, especially in relation to child marriage, our data showed distinct variations in response patterns from Tripoli relative to the other regions. To gain a deeper understanding of these contrasting experiences and to ascertain the unique needs of Syrian refugees in Tripoli, we conducted a mixed-methods analysis.MethodsWe conducted a mixed-methods, cross-sectional study in Lebanon in July–August 2016 using Cognitive Edge’s SenseMaker®. Participants were self-identified Syrian refugees and Lebanese men aged 14 and older. For dyad questions, Kruskal–Wallis H tests with chi-squared statistics compared different geographic subgroups and post-hoc Fisher’s Least Squares Difference analysis identified which groups differed. For triad data, geometric means and 95% confident ellipses were used to compare subgroups. Qualitative analysis of narratives from Tripoli complemented the quantitative results.ResultsWe collected 1422 narratives from 1346 unique participants, including 464 participants from Tripoli. From the quantitative data, three significant response pattern differences between participants in Tripoli and participants in other locations were noted: (a) Syrian fathers in Tripoli perceived that additional programs/services were needed to support Syrian girls, (b) men in Tripoli reported that financial insecurity had contributed to the experiences of Syrian girls, and (c) Syrian girls and mothers in Tripoli perceived that girls were ‘protected too much’. These differences may be driven by the economic and political subnational differences unique to Tripoli.ConclusionsOur subnational analysis identified a need for programs and services, financial security, and safety for Syrian girls in Tripoli. Different perspectives in Tripoli highlight that the experiences, concerns, and needs of Syrian refugees in Lebanon are not homogenous across locations. Localized contextualization is needed to guide the development of tailored approaches to support and to inform the distribution of resources.

Species depletion profiles as an alternative to streamflow alteration thresholds in a hydroecological risk assessment

Tradeoffs between human demands and ecological consequences of water resources necessitate setting limits to the hydrologic alteration of rivers – these limits or thresholds are required to prescribe environmental flows to maintain the ecological integrity of river ecosystems. Ideally, water managers could derive these thresholds empirically from hydroecological studies. Unfortunately, recent synthesis studies suggest that clear thresholds for terrestrial and aquatic ecosystems are elusive – if they exist at all. The field of ecological risk assessment (ERA) offers many approaches to describe and manage the prevalence and threat of an environmental stressor and establish limits of that stressor. This study introduces a hydroecological risk assessment (HERA) to identify thresholds of hydrologic alteration using an approach from ecological risk assessment and a stressor derived from publicly available hydrologic data. Rather than a single threshold value for ecological responses to hydrologic alteration, this study found that species exhibit variable patterns of response to depletion across their ranges – what we term Species Depletion Profiles (SDPs). These SDPs correlate with population health of the species in question, with similarities in conservation status and distribution evident among species with similar SDPs. Our results suggest that a well-used approach common to aquatic ecotoxicology has potential application in developing environmental flow guidelines for protection and remediation of riverine systems subject to anthropogenic influences where specific flow-ecology relationships are unknown.

Improving Soil Fertility and Maize Growth in Suboptimal Land Through Application of Humic Acid

Humic acid (HA) has been reported to increase plant growth and crop yields, as well as improve soil fertility. However, the potential utilization of HA extracted from various organic waste composts as organic amendment in suboptimal soils has not been studied in depth. The experiment used a two-factor Completely Randomized Design (CRD) with three replications. Four types of HA were used, namely bagasse HA (BHA), water hyacinth HA (WHA), market waste HA (MHA), and commercial HA (CHA). It also comprised of four doses HA i.e., 0.05, 0.10, 0.15 and 0.20% (of soil on w/w base). The results revealed that fluctuations in soil pH and nutrient release with the HA application had a variable quadratic response pattern. Organic carbon increased by 17%, while total N and available P decreased by 5% and 38.6% during the last weeks of incubation. The HA application could improve the growth response and nutrient uptake of maize significantly. CHA0.20% was the best interaction treatment which had the highest average value on dry weight and NPK uptake, which were 98.0 g pot-1, 178.8 mg plant-1, 27.4 mg plant-1 and 216.9 mg plant-1, respectively. The scanning electron microscopic (SEM) showed that HA could increase in the length and density of maize root hairs. Furthermore, the HA application significantly increased pH, CEC, C-organic content and availability of soil nutrients.

Non-parametric synergy modeling of chemical compounds with Gaussian processes

BackgroundUnderstanding the synergetic and antagonistic effects of combinations of drugs and toxins is vital for many applications, including treatment of multifactorial diseases and ecotoxicological monitoring. Synergy is usually assessed by comparing the response of drug combinations to a predicted non-interactive response from reference (null) models. Possible choices of null models are Loewe additivity, Bliss independence and the recently rediscovered Hand model. A different approach is taken by the MuSyC model, which directly fits a generalization of the Hill model to the data. All of these models, however, fit the dose–response relationship with a parametric model.ResultsWe propose the Hand-GP model, a non-parametric model based on the combination of the Hand model with Gaussian processes. We introduce a new logarithmic squared exponential kernel for the Gaussian process which captures the logarithmic dependence of response on dose. From the monotherapeutic response and the Hand principle, we construct a null reference response and synergy is assessed from the difference between this null reference and the Gaussian process fitted response. Statistical significance of the difference is assessed from the confidence intervals of the Gaussian process fits. We evaluate performance of our model on a simulated data set from Greco, two simulated data sets of our own design and two benchmark data sets from Chou and Talalay. We compare the Hand-GP model to standard synergy models and show that our model performs better on these data sets. We also compare our model to the MuSyC model as an example of a recent method on these five data sets and on two-drug combination screens: Mott et al. anti-malarial screen and O’Neil et al. anti-cancer screen. We identify cases in which the HandGP model is preferred and cases in which the MuSyC model is preferred.ConclusionThe Hand-GP model is a flexible model to capture synergy. Its non-parametric and probabilistic nature allows it to model a wide variety of response patterns.

Comprehensive Assessment of Visual Perceptual Skills in Autism Spectrum Disorder.

The purpose of the current study was to assess meaningful variability in visual-perceptual skills using a standardized assessment of visual perception, the Test of Visual Perceptual Skills (TVPS), across children with and without autism spectrum disorder (ASD). In addition to assessing overall accuracy across subtests of the TVPS, we also assessed response variability at the item-level, and the linear relationship between quantitative measures of ASD symptoms, task performance, and item-level variance. We report a significant linear relationship between ASD features and performance on the TVPS Figure Ground subtest. Additionally, results of an item-level analysis point to a significant relationship between within-task variability on the Figure Ground subtest and quantitative ASD traits, with a less variable response pattern being associated with increased ASD symptoms. Findings presented here suggest variability in perceptual processing across ASD may be influenced by individual differences in trait distribution.

Comparison of Attention-Deficit Hyperactivity Disorder in Typically Developing Children and Children with Down Syndrome.

This study aimed to evaluate attention-deficit hyperactivity disorder (ADHD) symptom patterns among children with Down syndrome (DS) with or without ADHD and typically developing (TD) children with ADHD. Parents and teachers rated symptoms of inattention, hyperactivity, and general behavioral concerns for 22 children with DS and comorbid diagnoses of ADHD (DS + ADHD), 66 gender-matched and age-matched children with DS with no diagnosis of ADHD (DS - ADHD), and 66 gender-matched and age-matched TD children with ADHD (TD + ADHD). Children with DS were recruited from the community. TD children with ADHD were recruited from a specialty clinic evaluating for ADHD. Parents tended to report higher scores of inattention and hyperactivity for TD children with ADHD compared with children with DS and no ADHD. Although mean ADHD symptom summary scores were not significantly different in DS + ADHD and DS - ADHD, specific parent-report items (e.g., distractibility and being "on the go") did tend to differentiate these groups. By contrast, teachers tended to report higher inattention and hyperactivity scores for DS + ADHD compared with both DS - ADHD and TD + ADHD. Specific teacher-reported items tending to differentiate DS + ADHD and DS - ADHD included difficulties following through on tasks, avoiding tasks, leaving one's seat, and excessive talking. Variability in response patterns between parent and teacher reports for children with and without DS highlights the need to evaluate ADHD symptoms across environments. Our findings also suggest specific items that may particularly be helpful in distinguishing children with DS who do and do not have ADHD, although replication is needed.

Quantitative multiplexed strategies for human Lyme disease serological testing.

Lyme disease, which is primarily caused by infection with the bacterium Borrelia burgdorferi in the United States or other Borrelia species internationally, presents an ongoing challenge for diagnostics. Serological testing is the primary means of diagnosis but testing approaches differ widely, with varying degrees of sensitivity and specificity. Moreover, there is currently no reliable test to determine disease resolution following treatment. A distinct challenge in Lyme disease diagnostics is the variable patterns of human immune response to a plurality of antigens presented by Borrelia spp. during the infection. Thus, multiplexed testing approaches that capture these patterns and detect serological response against multiple antigens may be the key to prompt, accurate Lyme disease diagnosis. In this review, current state-of-the-art multiplexed diagnostic approaches are presented and compared with respect to their diagnostic accuracy and their potential for monitoring response to treatment.

Gamma Knife Thalamotomy for a Medically Refractory Tremors: Longitudinal Evaluation of Clinical Effects and MRI Response Patterns.

The present longitudinal study evaluated the results of Gamma Knife surgery (GKS) for medically refractory tremors. The outcome after Gamma Knife thalamotomy targeting the ventral intermediate nucleus (VIM) was analyzed in 17 patients (9 men and 8 women; mean age 72years) with either Parkinson's disease or an essential tremor, who were followed up for at least 2years after treatment. Clinical and magnetic resonance imaging (MRI) examinations were done before and every 3months after GKS. The mean rates of symptom improvement (a decrease in the tremor frequency) were 6%, 39%, 63%, and 64% at 3, 6, 12, and 24monthsafter treatment, respectively. The defined MRI response patterns included a minimum reaction (in 3 patients), a normal reaction (in 11 patients), and a hyperreaction (in 3 patients). They were not associated with any evaluated pretreatment, radiosurgical, or outcome parameter, although 2 patients with a hyperreaction exhibited mild-to-moderate motor weakness in the contralateral limbs. Linear contrasting of the border between the thalamus and the internal capsule adjacent to the lesion site was noted on follow-up MRI in 13 cases and was associated with a higher symptom improvement rate. GKS allows effective and safe management of medically refractory tremors. The treatment is characterized by variable MRI response patterns. Some imaging findings during follow-up may be associated with clinical effects.

Stacking Agricultural Management Tactics to Promote Improvements in Soil Structure and Microbial Activities

Linking agricultural management tactics to quantifiable changes in soil health-related properties is a key objective for increasing adoption of the most favorable management practices. We used two long-term, no-till cropping studies to illustrate the variable patterns of response of soil structure indices and microbial activity to additional management tactics, including crop rotational diversity, residue management and cover cropping. We found that observable effects of management tactics on soil properties were often dependent on the current crop phase sampled, even though the treatments were well-established. In some cases, a single additional management tactic produced a response, two tactics each produced a response and sometimes there were interactions between tactics. However, importantly, we never observed a negative effect for any of the response variables when stacking soil health building practices in no-till cropping systems. The collective results from the two field studies illustrate that soil health improvements with stacking management tactics are not always simply additive and are affected by temporal relationships inherent to the treatments. We conclude that the implementation of multiple positive management tactics increases the likelihood that improvements in soil properties can be documented with one or more of the proxy measures for soil health.

Quantity, quality, both or neither? Vowel contrasts in Hakha Chin monophthongs

Hakha Chin—a Tibeto-Burman language spoken in Chin State in western Myanmar—is reported to have phonemic length distinctions in its monophthongs (Melnik, 1997; Peterson, 2003; Maddieson, 2004) (e.g., [ii] vs. [i], [aa] vs. [a]). These pairs are also sometimes represented with tense/lax vowels (e.g., [i] vs. [ɪ], [a] vs. [ə]) (Peterson, 2017). Indeed, the results of a perception study conducted by Mortenson and Van Bik (2002) found variable response patterns in different dialect groups. Listeners from Hakha, the city after which the language is named, relied heavily on spectral cues related to quality to distinguish between long and short vowels, while listeners from the town of Thanthlang relied mainly on durational cues to perform the same task. In the current study, we present the first instrumental acoustic analysis of Hakha Chin vowel quality in order to aid in elucidating the nature of the contrast. Data from three college-aged native speakers (two male) suggest that neither duration nor quality play key roles in distinguishing between the so-called long and short vowels of Hakha Chin. Rather, as originally suggested by Maddieson (2004), the length associated with long vowels is mainly realized through lengthening of sonorant codas.

Wnt7a induces satellite cell expansion, myofiber hyperplasia and hypertrophy in rat craniofacial muscle

Craniofacial muscles drive critical functions in the head, including speech, feeding and expression. Compared with their counterparts in trunk and limbs, craniofacial muscles are of distinct embryonic origins, which might consequently lead to different growth patterns and regenerative potential. In this study, rat levator veli palatini muscle and masseter muscle were compared with tibialis anterior muscle in their response to exogenous Wnt7a stimulus, which has been proved effective in promoting muscle regeneration in the limbs. Histological, cellular and molecular analyses were performed both under basal condition and after a single dose injection of recombinant human Wnt7a. Under basal condition, levator veli palatini muscle demonstrated considerably more satellite cells than the others. After Wnt7a administration, regeneration-related activities, including satellite cell expansion, myofiber hyperplasia and hypertrophy were generally observed in all three muscles, but with obvious differences in the extent. The composition of fast/slow myofibers underwent substantial alterations, and the pattern varied among the three muscles. Location-specific alterations in the expression level of core components in planar cell polarity pathway, Akt/mTOR pathway and myostatin pathway were also observed. In conclusion, both craniofacial and limb muscles could be effectively expanded by exogenous Wnt7a stimulus, but muscle-to-muscle variations in response patterns existed.

Variable behavior and repeated learning in two mouse strains: Developmental and genetic contributions

Behavioral inflexibility is often assessed using reversal learning tasks, which require a relatively low degree of response variability. No studies have assessed sensitivity to reinforcement contingencies that specifically select highly variable response patterns in mice, let alone in models of neurodevelopmental disorders involving limited response variation. Operant variability and incremental repeated acquisition (IRA) were used to assess unique aspects of behavioral variability of two mouse strains: BALB/c, a model of some deficits in ASD, and C57Bl/6. On the operant variability task, BALB/c mice responded more repetitively during adolescence than C57Bl/6 mice when reinforcement did not require variability but responded more variably when reinforcement required variability. During IRA testing in adulthood, both strains acquired an unchanging, performance sequence equally well. Strain differences emerged, however, after novel learning sequences began alternating with the performance sequence: BALB/c mice substantially outperformed C57Bl/6 mice. Using litter-mate controls, it was found that adolescent experience with variability did not affect either learning or performance on the IRA task in adulthood. These findings constrain the use of BALB/c mice as a model of ASD, but once again reveal this strain is highly sensitive to reinforcement contingencies and they are fast and robust learners.

Identification of a Novel, EBV-Based Antibody Risk Stratification Signature for Early Detection of Nasopharyngeal Carcinoma in Taiwan.

Background Epstein-Barr virus (EBV) is necessary for the development of nasopharyngeal carcinoma (NPC). By adulthood, approximately 90% of individuals test EBV-positive, but only a fraction develop cancer. Factors that identify which individuals are most likely to develop disease, including differential antibody response to the virus, could facilitate detection at early stages when treatment is most effective.Methods We measured anti-EBV IgG and IgA antibody responses in 607 Taiwanese individuals. Antibodies were measured using a custom protein microarray targeting 199 sequences from 86 EBV proteins. Variation in response patterns between NPC cases and controls was used to develop an antibody-based risk score for predicting NPC. The overall accuracy [area under the curve (AUC)] of this risk score, and its performance relative to currently used biomarkers, was evaluated in two independent Taiwanese cohorts.Findings Levels of 60 IgA and 73 IgG anti-EBV antibodies differed between stage I/IIa NPC cases and controls (P < 0.0002). Risk prediction analyses identified antibody targets that best discriminated NPC status-BXLF1, LF2,BZLF1, BRLF1, EAd, BGLF2, BPLF1, BFRF1, and BORF1. When combined with currently used VCA/EBNA1 IgA biomarkers, the resulting risk score predicted NPC with 93% accuracy (95% CI, 87%-98%) in the general Taiwanese population, a significant improvement beyond current biomarkers alone (82%; 95% CI, 75%-90%, P ≤ 0.01). This EBV-based risk score also improved NPC prediction in genetically high-risk families (89%; 95% CI, 82%-96%) compared with current biomarkers (78%; 95% CI, 66%-90%, P ≤ 0.03).Interpretation We identified NPC-related differences in 133 anti-EBV antibodies and developed a risk score using this microarray dataset that targeted immune responses against EBV proteins from all stages of the viral life cycle, significantly improving the ability to predict NPC. Clin Cancer Res; 24(6); 1305-14. ©2017 AACR.

The Swedish RAND-36 Health Survey - reliability and responsiveness assessed in patient populations using Svensson\u2019s method for paired ordinal data

BackgroundThe Short Form 36-Item Survey is one of the most commonly used instruments for assessing health-related quality of life. Two identical versions of the original instrument are currently available: the public domain, license free RAND-36 and the commercial SF-36.RAND-36 is not available in Swedish. The purpose of this study was threefold: to translate and culturally adapt the RAND-36 into Swedish; to evaluate its reliability and responsiveness using Svensson’s method for paired ordered categorical data; and to assess the usability of an electronic version of the questionnaire.The translation process included forward and backward translations and reconciliation. Test-retest reliability was examined during a period of two-weeks in 84 patients undergoing dialysis for chronic kidney disease. Responsiveness was examined in 97 patients before and 2 months after a cardiac rehabilitation program. Usability tests and cognitive debriefing of the electronic questionnaire were carried out with 18 patients.ResultsThe Swedish translation of the RAND-36 was conceptually equivalent to the English version. Test-retest reliability was supported by non-significant relative position (RP) values among dialysis patients for all RAND-36 subscales (range − 0.02 to 0.10; all confidence intervals (CI) included zero). Responsiveness was demonstrated by significant improvements in RP values among cardiac rehabilitation patients for all subscales (range 0.22–0.36; lower limits of all CI > 0.1) except two subscales (General health, RP -0.02; CI -0.13 to 0.10; and Role functioning/emotional, RP 0.03; CI -0.09 to 0.16). In cardiac rehabilitation patients, sizable individual variation (RV > 0.2) was also shown for the Pain, Energy/fatigue and Social functioning subscales.The electronic version of RAND-36 was found easy and intuitive to use.ConclusionsOur results provide evidence supporting the reliability and responsiveness of the newly translated Swedish RAND-36 and the user-friendliness of the electronic version. Svensson’s method for paired ordinal data was able to characterize not only the direction and size of differences among the patients’ responses at different time points but also variations in response patterns within groups. The method is therefore, besides being suitable for ordinal data, also an important and novel tool for gaining insights into patients’ response patterns to treatment or interventions, thus informing individualized care.

Persistence during and resurgence following noncontingent reinforcement implemented with and without extinction.

Noncontingent reinforcement (NCR) is typically implemented with extinction (EXT) for destructive behavior reinforced by social consequences and without EXT for destructive behavior reinforced by sensory consequences. Behavioral momentum theory (BMT) predicts that responding will be more persistent, and treatment relapse in the form of response resurgence more likely, when NCR is implemented without EXT due to the greater overall rate of reinforcement associated with this intervention. We used an analogue arrangement to test these predictions of BMT by comparing NCR implemented with and without EXT. For two of three participants, we observed more immediate reductions in responding during NCR without EXT. However, for all participants, NCR without EXT produced greater resurgence than NCR with EXT when we discontinued all reinforcers during an EXT Only phase, although there was variability in response patterns across and within participants. Implications for treatment of destructive behavior using NCR are discussed.

Modeling heat stress under different environmental conditions

Renewed interest in heat stress effects on livestock productivity derives from climate change, which is expected to increase temperatures and the frequency of extreme weather events. This study aimed at evaluating the effect of temperature and humidity on milk production in highly selected dairy cattle populations across 3 European regions differing in climate and production systems to detect differences and similarities that can be used to optimize heat stress (HS) effect modeling. Milk, fat, and protein test day data from official milk recording for 1999 to 2010 in 4 Holstein populations located in the Walloon Region of Belgium (BEL), Luxembourg (LUX), Slovenia (SLO), and southern Spain (SPA) were merged with temperature and humidity data provided by the state meteorological agencies. After merging, the number of test day records/cows per trait ranged from 686,726/49,655 in SLO to 1,982,047/136,746 in BEL. Values for the daily average and maximum temperature-humidity index (THIavg and THImax) ranges for THIavg/THImax were largest in SLO (22–74/28–84) and shortest in SPA (39–76/46–83). Change point techniques were used to determine comfort thresholds, which differed across traits and climatic regions. Milk yield showed an inverted U-shaped pattern of response across the THI scale with a HS threshold around 73 THImax units. For fat and protein, thresholds were lower than for milk yield and were shifted around 6 THI units toward larger values in SPA compared with the other countries. Fat showed lower HS thresholds than protein traits in all countries. The traditional broken line model was compared with quadratic and cubic fits of the pattern of response in production to increasing heat loads. A cubic polynomial model allowing for individual variation in patterns of response and THIavg as heat load measure showed the best statistical features. Higher/lower producing animals showed less/more persistent production (quantity and quality) across the THI scale. The estimated correlations between comfort and THIavg values of 70 (which represents the upper end of the THIavg scale in BEL-LUX) were lower for BEL-LUX (0.70–0.80) than for SPA (0.83–0.85). Overall, animals producing in the more temperate climates and semi-extensive grazing systems of BEL and LUX showed HS at lower heat loads and more re-ranking across the THI scale than animals producing in the warmer climate and intensive indoor system of SPA.

Weighing the evidence: Variance in brain responses to milkshake receipt is predictive of eating behavior

Variations in brain responses to sensory stimuli are typically considered to lack information content and treated as “noise”. Alternatively, variable response patterns may reflect the adjustment of biological parameters to external factors. We used functional magnetic resonance imaging in healthy non-dieting individuals to test whether intra-individual variation in brain response to the receipt of milkshake is associated with a range of behavioral and metabolic parameters. We found that, following a meal, high variability in nucleus accumbens (NAcc) response to milkshake is associated with higher body mass index, greater dietary disinhibition, more variable ad libitum food consumption, faster increases in plasma insulin, faster decreases in plasma glucose, and greater weight loss over 1year. Our results thus uncover a series of physiological parameters encrypted as variable responses in NAcc to food stimuli. They also suggest that variations in striatal activity regulate the activation of behavioral and metabolic responses to food availability.