Telomere-lengthening germline variants predispose to a syndromic papillary thyroid cancer subtype.

Papillary thyroid cancer (PTC) is the most common endocrine malignancy. 10% to 15% of individuals show familial clustering with three or more affected members, but the factors underlying this risk are unknown. In a group of recently studied individuals with POT1 pathogenic variants and ultra-long telomere length, PTC was the second most common solid tumor. We tested whether variants in POT1 and four other telomere-maintenance genes associated with familial cancer underlie PTC susceptibility. Among 470 individuals, we identified pathogenic or likely pathogenic variants in three genes encoding telomere-binding proteins: POT1, TINF2, and ACD. They were found in 4.5% and 1.5% of familial and unselected cases, respectively. Individuals harboring these variants had ultra-long telomere length, and 15 of 18 (83%) developed other cancers, of which melanoma, lymphoma, and sarcoma were most common. Among individuals with PTC and melanoma, 22% carried a deleterious germline variant, suggesting that a long telomere syndrome might be clinically recognizable. Successive generations had longer telomere length than their parents and, at times, developed more cancers at younger ages. Tumor sequencing identified a single oncogenic driver, BRAF p.Val600Glu, in 10 of 10 tumors studied, but no telomere-maintenance mechanism, including at the TERT promoter. These data identify a syndromic subset of PTCs with locus heterogeneity and telomere lengthening as a convergent mechanism. They suggest these germline variants lower the threshold to cancer by obviating the need for an acquired telomere-maintenance mechanism in addition to sustaining the longevity of oncogenic mutations.

Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease.

Autosomal-dominant ataxia with sensory and autonomic neuropathy is a highly specific combined phenotype that we described in two Swedish kindreds in 2014; its genetic cause had remained unknown. Here, we report the discovery of exonic GGC trinucleotide repeat expansions, encoding poly-glycine, in zinc finger homeobox 3 (ZFHX3) in these families. The expansions were identified in whole-genome datasets within genomic segments that all affected family members shared. Non-expanded alleles carried one or more interruptions within the repeat. We also found ZFHX3 repeat expansions in three additional families, all from the region of Skåne in southern Sweden. Individuals with expanded repeats developed balance and gait disturbances at 15 to 60 years of age and had sensory neuropathy and slow saccades. Anticipation was observed in all families and correlated with different repeat lengths determined through long-read sequencing in two family members. The most severely affected individuals had marked autonomic dysfunction, with severe orthostatism as the most disabling clinical feature. Neuropathology revealed p62-positive intracytoplasmic and intranuclear inclusions in neurons of the central and enteric nervous system, as well as alpha-synuclein positivity. ZFHX3 is located within the 16q22 locus, to which spinocerebellar ataxia type 4 (SCA4) repeatedly had been mapped; the clinical phenotype in our families corresponded well with the unique phenotype described in SCA4, and the original SCA4 kindred originated from Sweden. ZFHX3 has known functions in neuronal development and differentiation n both the central and peripheral nervous system. Our findings demonstrate that SCA4 is caused by repeat expansions in ZFHX3.

Deletion of the Clock Gene Bmal2 Leads to Alterations in Hypothalamic Clocks, Circadian Regulation of Feeding, and Energy Balance.

BMAL2 (ARNTL2) is a paralog of BMAL1 that can form heterodimers with the other circadian factors CLOCK and NPAS2 to activate transcription of clock and clock-controlled genes. To assess a possible role of Bmal2 in the circadian regulation of metabolism, we investigated daily variations of energy metabolism, feeding behavior, and locomotor behavior, as well as ability to anticipate restricted food access in male mice knock-out for Bmal2 (B2KO). While their amount of food intake and locomotor activity were normal compared with wild-type mice, B2KO mice displayed increased adiposity (1.5-fold higher) and fasted hyperinsulinemia (fourfold higher) and tended to have lower energy expenditure at night. Impairment of the master clock in the suprachiasmatic nuclei was evidenced by the shorter free-running period (-14 min/cycle) of B2KO mice compared with wild-type controls and by a loss of daily rhythmicity in expression of intracellular metabolic regulators (e.g., Lipoprotein lipase and Uncoupling protein 2). The circadian window of eating was longer in B2KO mice. The circadian patterns of food intake and meal numbers were bimodal in control mice but not in B2KO mice. In response to restricted feeding, food-anticipatory activity was almost prevented in B2KO mice, suggesting altered food clock that controls anticipation of food availability. In the mediobasal hypothalamus of B2KO mice, expression of genes coding orexigenic neuropeptides (including Neuropeptide y and Agouti-Related Peptide) was downregulated, while Lipoprotein lipase expression lost its rhythmicity. Together, these data highlight that BMAL2 has major impacts on brain regulation of metabolic rhythms, sleep-wake cycle, and food anticipation.

Multitissue Circadian Proteome Atlas of WT and Per1-/-/Per2-/- Mice.

The molecular basis of circadian rhythm, driven by core clock genes such as Per1/2, has been investigated on the transcriptome level, but not comprehensively on the proteome level. Here we quantified over 11,000 proteins expressed in eight types of tissues over 46 h with an interval of 2 h, using WT and Per1/Per2 double knockout mouse models. The multitissue circadian proteome landscape of WT mice shows tissue-specific patterns and reflects circadian anticipatory phenomena, which are less obvious on the transcript level. In most peripheral tissues of double knockout mice, reduced protein cyclers are identified when compared with those in WT mice. In addition, PER1/2 contributes to controlling the anticipation of the circadian rhythm, modulating tissue-specific cyclers as well as key pathways including nucleotide excision repair. Severe intertissue temporal dissonance of circadian proteome has been observed in the absence of Per1 and Per2. The γ-aminobutyric acid might modulate some of these temporally correlated cyclers in WT mice. Our study deepens our understanding of rhythmic proteins across multiple tissues and provides valuable insights into chronochemotherapy. The data are accessible at https://prot-rhythm.prottalks.com/.

Anticipation in families with MLH1-associated Lynch syndrome.

BACKGROUND: Lynch syndrome (LS) is an autosomal-dominant, hereditary cancer predisposition syndrome caused by pathogenic variants (PVs) in one of the mismatch-repair genes MLH1, MSH2/EPCAM, MSH6, or PMS2. Individuals who have MLH1 PVs have high lifetime risks of colorectal cancer (CRC) and endometrial cancer (EC). There is controversy regarding whether a younger age at diagnosis (or anticipation) occurs in MLH1-associated LS. The objective of this study was to assess anticipation in families with MLH1-associated LS by using statistical models while controlling for potential confounders. METHODS: Data from 31 families with MLH1 PVs were obtained from an academic registry. Wilcoxon signed-rank tests on parent-child-pairs as well as parametric Weibull and semiparametric Cox proportional hazards and Cox mixed-effects models were used to calculate hazard ratios or to compare mean ages at CRC/EC diagnosis by generation. Models were also corrected for ascertainment bias and birth-cohort effects. RESULTS: A trend toward younger ages at diagnosis of CRC/EC in successive generations, ranging from 3.2 to 15.7 years, was observed in MLH1 PV carrier families. A greater hazard for cancer in younger generations was not precluded by the inclusion of birth cohorts in the model. Individuals who had MLH1 variants with no Mlh1 activity were at a 78% greater hazard for CRC/EC than those who retained Mlh1 activity. CONCLUSIONS: The current results demonstrated evidence in support of anticipation in families with MLH1-associated LS across all statistical models. Mutational effects on Mlh1 activity influenced the hazard for CRC/EC. Screening based on the youngest age of cancer diagnosis in MLH1-LS families is recommended.

Clinical and Genetic Spectrum in a Large Cohort of Hereditary Spastic Paraplegia.

BACKGROUND: Next-generation sequencing-based molecular assessment has benefited the diagnosis of hereditary spastic paraplegia (HSP) subtypes. However, the clinical and genetic spectrum of HSP due to large fragment deletions/duplications has yet to be fully defined. OBJECTIVE: We aim to better characterize the clinical phenotypes and genetic features of HSP and to provide new thoughts on diagnosis. METHODS: Whole-exome sequencing (WES) was performed in patients with clinically suspected HSP, followed by multiple ligation-dependent probe amplification (MLPA) sequentially carried out for those with negative findings in known causative genes. Genotype-phenotype correlation analyses were conducted under specific genotypes. RESULTS: We made a genetic diagnosis in 60% (162/270) of patients, of whom 48.9% (132/270) had 24 various subtypes due to point mutations (SPG4/SPG11/SPG35/SPG7/SPG10/SPG5/SPG3A/SPG2/SPG76/SPG30/SPG6/SPG9A/SPG12/SPG15/SPG17/SPG18/SPG26/SPG49/SPG55/SPG56/SPG57/SPG62/SPG78/SPG80). Thirty patients were found to have causative rearrangements by MLPA (11.1%), among which SPG4 was the most prevalent (73.3%), followed by SPG3A (16.7%), SPG6 (3.3%), SPG7 (3.3%), and SPG11 (3.3%). Clinical analysis showed that some symptoms were often related to specific subtypes, and rearrangement-related SPG3A patients seemingly had later onset. We observed a presumptive anticipation among SPG4 and SPG3A families due to rearrangement. CONCLUSIONS: Based on the largest known Asian HSP cohort, including the largest subgroup of rearrangement-related pedigrees, we gain a comprehensive understanding of the clinical and genetic spectrum of HSP. We propose a diagnostic flowchart to sequentially detect the causative genes in practice. Large fragment mutations account for a considerable proportion of HSP, and thus, MLPA screening acts as a beneficial supplement to routine WES. © 2024 International Parkinson and Movement Disorder Society.

Emerging Perspectives on Neuroprotection.

Neuroprotection aims to safeguard neurons from damage caused by various factors like stress, potentially leading to the rescue, recovery, or regeneration of the nervous system and its functions [J Clin Neurosci. 2002;9(1):4-8]. Conversely, neuroplasticity refers to the brain's ability to adapt and change throughout life, involving structural and functional alterations in cells and synaptic transmission [Neural Plast. 2014;2014:541870]. Neuroprotection is a broad and multidisciplinary field encompassing various approaches and strategies aimed at preserving and promoting neuronal health. It is a critical area of research in neuroscience and neurology, with the potential to lead to new therapies for a wide range of neurological disorders and conditions. Neuroprotection can take various forms and may involve pharmacological agents, lifestyle modifications, or behavioral interventions. Accordingly, also the perspective and the meaning of neuroprotection differs due to different angles of interpretation. The primary interpretation is from the pharmacological point of view since the most consistent data come from this field. In addition, we will discuss also alternative, yet less considered, perspectives on neuroprotection, focusing on specific neuroprotective targets, interactions with surrounding microglia, different levels of neuroprotective effects, the reversive/adaptative dimension, and its use as anticipatory/prophylactic intervention.

The concealed information test with a continuously moving stimulus.

The Concealed Information Test (CIT) aims to extract concealed crime-related knowledge using physiological measures. In the present study, we propose a new variant of the CIT that contains a continuously moving stimulus. A total of 81 participants were either informed or not about the specific location of an upcoming terrorist attack. The CIT consisted of a map with a superimposed moving dot, combined with measurements of respiration and electrodermal activity. The results revealed both respiratory suppression and an increase in skin conductance when the moving dot passed the target location only in informed participants. These findings showed that this new variant of the CIT can differentiate between groups of informed and uninformed individuals and an exploratory analysis revealed it can help narrow down a search area.

Unveiling the invisible: receivers use object weight cues for grip force planning in handover actions.

Handover actions are part of our daily lives. Whether it is the milk carton at the breakfast table or tickets at the box office, we usually perform these joint actions without much conscious attention. The individual actions involved in handovers, that have already been studied intensively at the level of individual actions, are grasping, lifting, and transporting objects. Depending on the object's properties, actors must plan their execution in order to ensure smooth and efficient object transfer. Therefore, anticipatory grip force scaling is crucial. Grip forces are planned in anticipation using weight estimates based on experience or visual cues. This study aimed to investigate whether receivers are able to correctly estimate object weight by observing the giver's kinematics. For this purpose, handover actions were performed with 20 dyads, manipulating the participant role (giver/receiver) and varying the size and weight of the object. Due to the random presentation of the object weight and the absence of visual cues, the participants were unaware of the object weight from trial to trial. Kinematics were recorded with a motion tracking system and grip forces were recorded with customized test objects. Peak grip force rates were used as a measure of anticipated object weight. Results showed that receiver kinematics are significantly affected by object weight. The peak grip force rates showed that receivers anticipate object weight, but givers not. This supports the hypothesis that receivers obtain information about the object weight by observing giver's kinematics and integrating this information into their own action execution.

Effects of different doses of caffeine on cognitive performance in healthy physically active individuals.

PURPOSE: Caffeine is a potent central nervous system stimulant that increases the activity of the prefrontal cortex and can improve various cognitive skills. An improvement in these cognitive skills can lead to further benefits in athletic performance. Therefore, it is necessary to clarify the dose-response of caffeine on cognitive performance. This study aimed to determine the effects of different doses of caffeine on sport-related cognitive aspects. METHODS: Twenty-nine healthy physically active young adults were recruited. All participants completed three trials under the following conditions: (a) placebo, (b) 3 mg/kg, or (c) 6 mg/kg body mass of caffeine. In each trial, different cognitive abilities were evaluated with the following battery of tests: reaction time (Dynavision™ D2), anticipation (Bassin Anticipation Timer), sustained attention (Go/No-Go and Eriksen Flanker Test) and memory tests. Moreover, the side effects and the perceived sensation index were recorded 24 h after each test. RESULTS: Reaction time only improved following 6 mg/kg of caffeine intake (Physical reaction time: -0.04 s, 95% CI -0.08 to -0.01 s, P = 0.036, d = 0.5; Motor reaction time: -0.04 s, 95% CI -0.07 to -0.01 s, P = 0.008, d = 0.6) compared to the placebo condition. Anticipation, sustained attention, and memory were not affected after either caffeine dose intake (all P > 0.05). In addition, the 6 mg/kg dose of caffeine augmented the occurrence of the side effects of increased activeness (P = 0.046) and nervousness (P = 0.001). CONCLUSION: Acute intake of 6 mg/kg caffeine is effective in improving reaction time despite increasing the occurrence of side effects in healthy physically active young adults. STUDY REGISTRATION: This study has been registered in ClinicalTrials whose ID is: NCT05995314 (2023-08-08).

Anticipatory and consummatory neural correlates of monetary and music rewarding stimuli.

Most of the literature on the neural bases of human reward and punishment processing has used monetary gains and losses, but less is known about the neurophysiological mechanisms underlying the anticipation and consumption of other types of rewarding stimuli. In the present study, EEG was recorded from 19 participants who completed a modified version of the Monetary Incentive Delay (MID) task. During the task, cues providing information about potential future outcomes were presented to the participants. Then, they had to respond rapidly to a target stimulus to win money or listening to pleasant music, or to avoid losing money or listening to unpleasant music. Results revealed similar responses for monetary and music cues, with increased activity for cues indicating potential gains compared to losses. However, differences emerged in the outcome phase between money and music. Monetary outcomes showed an interaction between the type of the cue and the outcome in the Feedback Related Negativity and Fb-P3 ERPs and increased theta activity increased for negative feedbacks. In contrast, music outcomes showed significant interactions in the Fb-P3 and theta activities. These findings suggest similar neurophysiological mechanisms in processing cues for potential positive or negative outcomes in these two types of stimuli.

Independent effects of emotional arousal and reward anticipation on episodic memory formation.

Events that elicit emotional arousal or are associated with reward are more likely remembered. Emotional arousal activates the amygdala and the central noradrenergic system, whereas reward anticipation results in an activity in the mesocorticolimbic dopaminergic system. The activation of both pathways enhances memory formation in the hippocampus where their effects are based on similar neural substrates, e.g. tagging of active hippocampal synapses. Moreover, emotional arousal and reward anticipation both enhance attention, which can also affect memory formation. In addition, both neuromodulators interact on the cellular level. Therefore, we tested in the current functional magnetic resonance imaging study whether simultaneously occurring emotional arousal and reward anticipation might have interacting effects on memory formation. We did not find evidence for such an interaction, neither on the behavioral nor on the neural level. Our results further suggest that reward anticipation enhances memory formation rather by an increase in anticipation-related arousal-reflected in activity in the dorsal anterior cingulate cortex-and not dopaminergic midbrain activity. Accompanying behavioral experiments indicated that the effect of reward anticipation on memory is (i) caused at least to some extent by anticipating the speeded response to obtain the reward and not by the valance of the outcome and (ii) can be observed already immediately after encoding, i.e. before consolidation.

Turning Attention Inside Out: How Working Memory Serves Behavior.

Flexible behavior requires guidance not only by sensations that are available immediately but also by relevant mental contents carried forward through working memory. Therefore, selective-attention functions that modulate the contents of working memory to guide behavior (inside-out) are just as important as those operating on sensory signals to generate internal contents (outside-in). We review the burgeoning literature on selective attention in the inside-out direction and underscore its functional, flexible, and future-focused nature. We discuss in turn the purpose (why), targets (what), sources (when), and mechanisms (how) of selective attention inside working memory, using visual working memory as a model. We show how the study of internal selective attention brings new insights concerning the core cognitive processes of attention and working memory and how considering selective attention and working memory together paves the way for a rich and integrated understanding of how mind serves behavior.

Earlier age of symptom onset in younger generation of familial cases of multiple sclerosis.

AIM: The aim of this study was to assess the prevalence of familial MS (fMS) in Belgrade MS population, discern the differences between the persons with fMS and sporadic MS, and to detect the presence of anticipation phenomenon in fMS patients. METHODS: The data on the demographic and clinical characteristics of MS patients was obtained from the Belgrade MS population Registry. In cases of vertical transmission of MS, the family members were divided into the younger and older generation, in order to assess the potential presence of anticipation phenomenon. To adjust for follow-up time bias, a secondary analysis including only patients who had the onset of symptoms before 39 years (75.percentile), and those who were 39 + years, was performed. RESULTS: The prevalence of fMS in Belgrade MS population is 6.4%. FMS cases had earlier age at MS symptom onset (30.4 vs. 32.3 years) compared to sporadic MS cohort. When comparing fMS cases across generations, the younger generation had significantly lower age at onset compared with the older one (25.8 vs. 35.7 years, p < 0.001). After adjustment for the different length of the follow-up, the difference in age at symptom onset between the groups was reduced, but it still existed and was statistically significant (30.0 years in younger vs. 36.4 years in older generation, p = 0.040). CONCLUSION: In our study, the analysis of fMS cases across generations, showed an earlier age of symptom onset in the younger generation, even after adjustment. These results indicate the possibility of existence of anticipation phenomenon.

Impact of temperature on physical and cognitive performance in elite female football players during intermittent exercise.

There is limited research on female football players, especially related to their physical and cognitive performance under different climactic conditions. We analyzed the impact of a hot environmental temperature on physical performance and anticipation in elite female football players during a fatigue-inducing intermittent protocol. Elite female players (n = 21) performed the countermovement jump (CMJ) and responded to filmed sequences of offensive play under two distinct environmental temperatures (i.e., mild environment temperature- 20°C and 30% rh versus hot environment temperature- 38°C and 80% rh), interspersed by 1-week interval. Linear mixed models were used. CMJ performance declined following the intermittent protocol on both temperature conditions (p < 0.05). Moreover, there were significant main effects for protocol on CMJ speed (m/s) (p = 0.001; ηp 2 = 0.12), CMJ power (p = 0.002; ηp 2 = 0.11), and CMJ Heightmax (p = 0.002; ηp 2 = 0.12). After performing the intermittent protocol, exposure to a hot temperature caused a greater decline in anticipation accuracy (mild temperature = 64.41% vs. hot temperature = 53.44%; p < 0.001). Our study shows impaired performance in elite female football players following an intermittent protocol under hot compared with mild environmental conditions. We report decreased performance in both CMJ and anticipation performance under hotter conditions. The results reveal that exposure to hot temperatures had a negative effect on the accuracy of their anticipatory behaviors. We consider the implication of the work for research and training interventions.

Saccade Latency and Metrics in the Interleaved Pro- and Anti-Saccade Task in Open Skill Sports Athletes.

Evidence has demonstrated that athletes exhibit superior cognitive performance associated with executive control. In the oculomotor system, this function has been examined using the interleaved pro-saccade and anti-saccade task (IPAST), wherein participants, prior to target appearance, are instructed to either automatically look at the peripheral target (pro-saccade) or suppress the automatic response and voluntarily look in the opposite direction (anti-saccade). While the IPAST has provided much insight into sensorimotor and inhibitory processing, it has yet to be performed in athletes. Moreover, limited research has examined saccade metrics in athletes. Here, we examined saccade latency and movement kinematics in the IPAST among athletes (N = 40) and nonathletes (NON) (N = 40). Higher direction error rates were obtained in the anti-saccade compared to the pro-saccade condition, with no differences between athletes and NON noted. Significantly faster saccade latencies were observed in athletes compared to NON in both conditions, in addition to faster pro-saccades compared to anti-saccades. Furthermore, athletes showed significantly higher frequencies and faster latencies of express saccades compared to NON in correct pro-saccades. Additionally, athletes exhibited significantly faster latencies of express saccades compared to NON in erroneous anti-saccades. Differences in saccade metrics between athletes and NON were not seen. Overall, these findings demonstrate that athletes display altered saccade performance likely associated with sensorimotor and preparatory processing, highlighting the potential of using IPAST to objectively investigate sensorimotor and cognitive functions in athletes.

The development of children's and adults' use of kinematic cues for visual anticipation and verbal prediction of action.

Expectations about how others' actions unfold in the future are crucial for our everyday social interactions. The current study examined the development of the use of kinematic cues for action anticipation and prediction in 3-year-olds, 4-year-olds, 10-year-olds, and adults in two experiments. Participants observed a hand repeatedly reaching for either a close or far object. The motor kinematics of the hand varied depending on whether the hand reached for the close or far object. We assessed whether participants would use kinematic cues to visually anticipate (Experiment 1; N=98) and verbally predict (Experiment 2; N=80) which object the hand was going to grasp. We found that only adults, but not 3- to 10-year-olds, based their visual anticipations on kinematic cues (Experiment 1). This speaks against claims that action anticipations are based on simulating others' motor processes and instead provides evidence that anticipations are based on perceptual mechanisms. Interestingly, 10-year-olds used kinematic cues to correctly verbally predict the target object, and 4-year-olds learned to do so over the trials (Experiment 2). Thus, kinematic cues are used earlier in life for explicit action predictions than for visual action anticipations. This adds to a recent debate on whether or not an implicit understanding of others' actions precedes their ability to verbally reason about the same actions.

Evaluating the role of binge planning and binge inevitability within affect regulation models of binge eating.

Affect regulation models posit that aversive affective states drive binge-eating behavior, which then regulates negative emotions. However, recent findings among individuals with binge-eating disorder (BED) suggest that food-related anticipatory processes may precede and potentially explain the negative affect thought to drive binge eating. Specifically, studies using ecological momentary assessment (EMA) demonstrate that the negative affective state of "Guilt" (from the Positive and Negative Affect Schedule) most strongly predicts later binge eating in the natural environment, and it has been hypothesized that planning a binge or feeling that a binge-eating episode is inventible may account for the increases in Guilt observed prior to binge episodes. In the present study, we tested the hypothesis that binge planning or inevitability may contribute to feelings of shame (a key facet of the broader Guilt construct), which then predict binge-eating episodes, using EMA in 43 individuals with BED. Consistent with hypotheses, feelings of binge inevitability and planning prospectively predicted binge-eating episodes. Further, binge planning predicted subsequent increases in shame. However, shame did not predict subsequent increases in binge planning. Finally, a mediation model revealed that binge planning (Time 1) predicted future binge eating (Time 3) directly and indirectly through increases in shame (Time 2). The results provide novel evidence that individuals with BED anticipate and actively plan for binge-eating episodes, and that binge planning may explain the increased shame/guilt typically observed before binge eating. Overall, accruing evidence suggests that negative affect, although predictive of binge eating, may be better conceptualized as a consequence of the anticipatory processes that lead to binge eating, rather than the starting point, at least among some individuals with BED. Future experimental research is needed to more conclusively test this hypothesis.

Two sources of uncertainty independently modulate temporal expectancy.

The environment is shaped by two sources of temporal uncertainty: the discrete probability of whether an event will occur and-if it does-the continuous probability of when it will happen. These two types of uncertainty are fundamental to every form of anticipatory behavior including learning, decision-making, and motor planning. It remains unknown how the brain models the two uncertainty parameters and how they interact in anticipation. It is commonly assumed that the discrete probability of whether an event will occur has a fixed effect on event expectancy over time. In contrast, we first demonstrate that this pattern is highly dynamic and monotonically increases across time. Intriguingly, this behavior is independent of the continuous probability of when an event will occur. The effect of this continuous probability on anticipation is commonly proposed to be driven by the hazard rate (HR) of events. We next show that the HR fails to account for behavior and propose a model of event expectancy based on the probability density function of events. Our results hold for both vision and audition, suggesting independence of the representation of the two uncertainties from sensory input modality. These findings enrich the understanding of fundamental anticipatory processes and have provocative implications for many aspects of behavior and its neural underpinnings.

Diagnosing by anticipation: Coordinating patient trajectories within and across social systems.

Anticipation is a fundamental aspect of social life and, following Weber, the hallmark of social action-it means trying to take others' responses to our actions into account when acting. In this article, we propose and argue the relevance of anticipation to the sociological study of diagnosis. To that end, we introduce and elaborate on the concept of diagnosing by anticipation. To diagnose by anticipation is to consider diagnoses as cultural objects imbued with meaning, to anticipate how others will respond to their meaning in situ and to adapt the choice of diagnosis to secure a desired outcome. Unlike prognosis, which seeks to predict the development of a disease, diagnosing by anticipation entails seeking to predict the development of a case and the effect of different diagnostic categories on its trajectory. Analytically, diagnosing by anticipation therefore involves a shift in diagnostic footing, from trying to identify what the case is a case of, to trying to identify which diagnosis will yield the desired case trajectory. This shift also implies a stronger focus on the mundane organisational work of operating diagnostic systems and coordinating case trajectories within and across social systems, to the benefit of the sociology of diagnosis.