Early versus Delayed Vitrectomy for Open Globe Injuries: A Systematic Review and Meta-Analysis.

Background: Open globe injuries (OGIs) are a leading cause of monocular blindness worldwide and require prompt intervention to prevent proliferative vitreoretinopathy (PVR) and endophthalmitis when serious intraocular damage occurs. The management of OGIs involves initial wound closure within 24 hours, followed by vitrectomy as a secondary surgery. However, there is a lack of consensus regarding the optimal timing of vitrectomy for maximizing visual outcomes. This meta-analysis aimed to investigate whether early or delayed vitrectomy leads to better outcomes in patients with OGIs. Methods: This review was conducted based on PRISMA guidelines. The Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched (October 23, 2023). Clinical studies that used vitrectomy to manage OGIs as early (within 7 days) or delayed (8-14 days) interventions were included. Randomized controlled trials (RCTs) and non-RCTs were appraised using the Cochrane risk of bias and JBI tools, respectively. Results: Eleven studies met the inclusion criteria and were included in the quantitative analyses. There were 235 patients with OGIs who received early intervention and 211 patients who received delayed intervention. The retina was reattached in 91% and 76% of the patients after early and delayed intervention, respectively. Traumatic PVR was present in 9% and 41% of the patients in the early and delayed groups, respectively. The odds of retinal reattachment after vitrectomy were greater in the early group (OR = 3.42, p = 0.010, 95% CI=1.34-8.72), and the odds of visual acuity ≥ 5/200 were 2.4 times greater in the early group. The incidence of PVR was significantly greater in the delayed surgery group (OR = 0.16, p < 0.0001; 95% CI=0.06-0.39), which also required more than one vitrectomy surgery. Conclusion: Early vitrectomy results in better postoperative visual acuity, a greater proportion of retinal reattachment, and a decreased incidence of PVR.

Optimizing trigger timing in minimal ovarian stimulation for In Vitro fertilization using machine learning models with random search hyperparameter tuning.

Various studies have emphasized the importance of identifying the optimal Trigger Timing (TT) for the trigger shot in In Vitro Fertilization (IVF), which is crucial for the successful maturation and release of oocytes, especially in minimal ovarian stimulation treatments. Despite its significance for the ultimate success of IVF, determining the precise TT remains a complex challenge for physicians due to the involvement of multiple variables. This study aims to enhance TT by developing a machine learning multi-output model that predicts the expected number of retrieved oocytes, mature oocytes (MII), fertilized oocytes (2 PN), and useable blastocysts within a 48-h window after the trigger shot in minimal stimulation cycles. By utilizing this model, physicians can identify patients with possible early, late, or on-time trigger shots. The study found that approximately 27 % of treatments administered the trigger shot on a suboptimal day, but optimizing the TT using the developed Artificial Intelligence (AI) model can potentially increase useable blastocyst production by 46 %. These findings highlight the potential of predictive models as a supplementary tool for optimizing trigger shot timing and improving IVF outcomes, particularly in minimal ovarian stimulation. The experimental results underwent statistical validation, demonstrating the accuracy and performance of the model. Overall, this study emphasizes the value of AI prediction models in enhancing TT and making the IVF process safer and more efficient.

The effect of birth timing manipulation around carnival on birth indicators in Brazil.

This paper studies the patterns and consequences of birth timing manipulation around the carnival holiday in Brazil. We document how births are displaced around carnival and estimate the effect of displacement on birth indicators. We show that there is extensive birth timing manipulation in the form of both anticipation and postponement that results in a net increase in gestational length and reductions in neonatal and early neonatal mortality, driven by postponed births that would otherwise happen through scheduled c-sections. We also find a reduction in birthweight for high-risk births at the bottom of the weight distribution, driven by anticipation. Therefore, restrictions on usual delivery procedures due to the carnival holiday can be both beneficial and detrimental, raising a double-sided issue to be addressed by policymakers.

A Second Introduction to the Neurobiology of Interval Timing.

Time is a critical variable that organisms must be able to measure in order to survive in a constantly changing environment. Initially, this paper describes the myriad of contexts where time is estimated or predicted and suggests that timing is not a single process and probably depends on a set of different neural mechanisms. Consistent with this hypothesis, the explosion of neurophysiological and imaging studies in the last 10 years suggests that different brain circuits and neural mechanisms are involved in the ability to tell and use time to control behavior across contexts. Then, we develop a conceptual framework that defines time as a family of different phenomena and propose a taxonomy with sensory, perceptual, motor, and sensorimotor timing as the pillars of temporal processing in the range of hundreds of milliseconds.

Diverse Time Encoding Strategies Within the Medial Premotor Areas of the Primate.

The measurement of time in the subsecond scale is critical for many sophisticated behaviors, yet its neural underpinnings are largely unknown. Recent neurophysiological experiments from our laboratory have shown that the neural activity in the medial premotor areas (MPC) of macaques can represent different aspects of temporal processing. During single interval categorization, we found that preSMA encodes a subjective category limit by reaching a peak of activity at a time that divides the set of test intervals into short and long. We also observed neural signals associated with the category selected by the subjects and the reward outcomes of the perceptual decision. On the other hand, we have studied the behavioral and neurophysiological basis of rhythmic timing. First, we have shown in different tapping tasks that macaques are able to produce predictively and accurately intervals that are cued by auditory or visual metronomes or when intervals are produced internally without sensory guidance. In addition, we found that the rhythmic timing mechanism in MPC is governed by different layers of neural clocks. Next, the instantaneous activity of single cells shows ramping activity that encodes the elapsed or remaining time for a tapping movement. In addition, we found MPC neurons that build neural sequences, forming dynamic patterns of activation that flexibly cover all the produced interval depending on the tapping tempo. This rhythmic neural clock resets on every interval providing an internal representation of pulse. Furthermore, the MPC cells show mixed selectivity, encoding not only elapsed time, but also the tempo of the tapping and the serial order element in the rhythmic sequence. Hence, MPC can map different task parameters, including the passage of time, using different cell populations. Finally, the projection of the time varying activity of MPC hundreds of cells into a low dimensional state space showed circular neural trajectories whose geometry represented the internal pulse and the tapping tempo. Overall, these findings support the notion that MPC is part of the core timing mechanism for both single interval and rhythmic timing, using neural clocks with different encoding principles, probably to flexibly encode and mix the timing representation with other task parameters.

The Interactions of Temporal and Sensory Representations in the Basal Ganglia.

In rodents and primates, interval estimation has been associated with a complex network of cortical and subcortical structures where the dorsal striatum plays a paramount role. Diverse evidence ranging from individual neurons to population activity has demonstrated that this area hosts temporal-related neural representations that may be instrumental for the perception and production of time intervals. However, little is known about how temporal representations interact with other well-known striatal representations, such as kinematic parameters of movements or somatosensory representations. An attractive hypothesis suggests that somatosensory representations may serve as the scaffold for complex representations such as elapsed time. Alternatively, these representations may coexist as independent streams of information that could be integrated into downstream nuclei, such as the substantia nigra or the globus pallidus. In this review, we will revise the available information suggesting an instrumental role of sensory representations in the construction of temporal representations at population and single-neuron levels throughout the basal ganglia.

Circadian misalignment proxies, BMI, and chronic conditions: the role for weekday to weekend sleep differences.

OBJECTIVE: To evaluate whether social jet lag (SJL) and weekend catch-up sleep (CUS), proxies of circadian misalignment, were associated with BMI and chronic conditions. METHODS: Participants (n = 2,050,18-65y) were part of a virtual cross-sectional and population-based research. We examined CUS and SJL as continuous and categorical (< 1 h,1-2 h, > 2 h). Linear regression analyses were performed to assess the differences in BMI (outcome) associated with CUS and SJL. Restricted cubic splines were performed to explore the shape of the relationship between weekday-to-weekend variability in sleep duration, midpoint, wake time, and bedtime. Logistic regression models were used to estimate ORs(95%CIs) for chronic conditions and overweight related to CUS and SJL. Analyses were adjusted for sleep duration, biological and behavior-related variables. RESULTS: We found a positive association of SJL and CUS with BMI. The effects remained even after adjustment for weekly sleep duration and demonstrated a proportional increase with the magnitude of sleep variability. Among participants with SJL > 2 h, BMI increased by 2.29 kg/m2 (95%CI:0.84;3.74,p:0.002). They also had 129% higher odds of chronic conditions (95%CI:1.16;4.52, p:0.01) and 119% higher odds of overweight (95%CI: 1.20;3.98,p:0.01). Individuals with CUS > 2 h presented 78% higher odds of overweight (95%CI:1.27;2.50,p:0.001) and an increase of 1.61 kg/m2 in BMI (95%CI: 0.81; 2.40,p < 0.001). CONCLUSIONS: Our findings, which demonstrate that even a slight weekend sleep extension and variability of just 1 h is associated with higher values of BMI, suggest incorporating measures for sleep consistency and regularity into clinical protocols and public health guidelines to prevent and treat obesity and related diseases.

Parapharyngeal and retropharyngeal infections in children: Kawasaki disease needs vigilance.

OBJECTIVE: Kawasaki Disease (KD) may mimic Parapharyngeal (PPI) and Retropharyngeal Infections (RPI), leading to misdiagnosis as Deep Neck Infections (DNIs). The treatment plans for the two diseases are different, and delayed treatment can lead to serious complications. Therefore, prompt diagnosis and management are necessary. This study was performed to evaluate the clinical features of KD mimicking DNIs and explore the treatment options. METHODS: Children with cellulitis or abscess in parapharyngeal or retropharyngeal space in neck CT were included in this study. The medical records of enrolled children were retrospectively reviewed. RESULTS: In total, 56 children were diagnosed with PPI or/and RPI. Twenty-two (39.3%) participants were eventually diagnosed with KD, and 34 (60.7%) were diagnosed with DNIs. Compared with the DNIs group, the KD group had a higher body temperature (p=0.007), and higher levels of AST (p=0.040), ALT (p=0.027), and ESR (p=0.030). Deep cervical cellulitis (p=0.005) were more common in the KD group. However, deep neck abscess often occurred in the DNIs group (p=0.002), with parapharyngeal abscess being the most common type of abscess (p=0.004). The KD mimicking DNIs cases did not respond to antibiotic treatment, but symptoms significantly improved after the use of Immunoglobulin (IVIG) and aspirin. CONCLUSION: Children with KD may exhibit retropharyngeal or parapharyngeal inflammation in the early stages. KD should be considered a differential diagnosis for children with DNIs, high fever, and no response to antibiotic therapy. Surgery in KD mimicking deep neck abscess requires caution. LEVEL OF EVIDENCE: I.

Effects of in ovo vaccination time on broiler performance parameters under field conditions.

Hatchery performance is often evaluated based on descriptors such as hatchability, 7-d mortality, and cost. In addition to these descriptors, it is useful to include in this analysis aspects of chick quality through post-hatch performance. Realizing the bird's complete genetic potential necessitates meeting various criteria, with effective support for the chick's immune system being among the pivotal factors. To be effective, in ovo vaccination systems must deliver the vaccines to specific sites in the egg, a circumstance that directly depends on when the injection is made. We examined production data to evaluate the impact of in ovo vaccination time on performance parameters of male Ross308AP chicks. A comprehensive survey was conducted examining records from 3,722 broiler flocks produced and raised by the same company under standard nutrition and management conditions. The selected data specifically pertained to flocks that underwent slaughter between 41 and 45 d. In our analysis, 4 different linear models were built, one for each response variable: mean weight (MW), body weight gain (BWG), corrected feeding conversion rate (cFCR), and total mortality (TM). The linear models used in the analyses included as main predictor the timing of in ovo vaccination (440, 444, 448, 452, 456, 458, and 460 h of incubation), and as additional predictors: age of the breeding flock (26-35, 36-55 and 56-66 wks old), slaughter age, identity of the hatchery, and the season at which the data was collected. Our results showed that the timing of in ovo vaccination significantly affected BWG and cFCR, with procedures performed at 460 h of incubation showing the best outcomes. Breeding flock age affected all response variables, with older breeding flocks delivering increased MW, BWG and TM, and middle-aged flocks increased cFCR. Increasing slaughter age reduced BWG while MW, cFCR and TM were all increased. These data emphasize the benefits of performing in ovo vaccination as close as possible to 460 h of incubation to extract the best BWG and cFCR from Ross308AP male broiler.

Time for What? Dissociating Explicit Timing Tasks through Electrophysiological Signatures.

Estimating durations between hundreds of milliseconds and seconds is essential for several daily tasks. Explicit timing tasks, which require participants to estimate durations to make a comparison (time for perception) or to reproduce them (time for action), are often used to investigate psychological and neural timing mechanisms. Recent studies have proposed that mechanisms may depend on specific task requirements. In this study, we conducted electroencephalogram (EEG) recordings on human participants as they estimated intervals in different task contexts to investigate the extent to which timing mechanisms depend on the nature of the task. We compared the neural processing of identical visual reference stimuli in two different tasks, in which stimulus durations were either perceptually compared or motorically reproduced in separate experimental blocks. Using multivariate pattern analyses, we could successfully decode the duration and the task of reference stimuli. We found evidence for both overlapping timing mechanisms across tasks as well as recruitment of task-dependent processes for comparing intervals for different purposes. Our findings suggest both core and specialized timing functions are recruited to support explicit timing tasks.

Determinants of Hispanic and non-Hispanic Workers' Intent to Work Past Age 65: An Analysis From the Life Course Perspective.

Background: The average retirement age in the United States (U.S.) has increased over the past few decades. However, the rate of increase for Hispanics is lower than that for non-Hispanics. For Hispanics, the decision to retire later may be more influenced by their migration history and context rather than health or finances. Objective: This study aims to explore the differences in the determinants of intentions to delay retirement (i.e., work beyond the age of 65) between Hispanics and non-Hispanic Whites in the U.S. Methods: A pooled sample was generated from all waves of the Health and Retirement Study (1992-2014), including a unique record for each non-institutionalized individual aged 55-61 who was employed. All eligible Hispanics (n = 3,663) were included, while a random sample of non-Hispanic Whites (n = 3,663) was selected. Logistic mixed models were conducted for each group, and a Two-fold Oaxaca-Blinder decomposition analysis was used to explore differences between the groups. Results: The results indicate that non-Hispanic Whites are more likely to plan to postpone retirement. Furthermore, significant differences were found between Hispanics and non-Hispanic Whites regarding their intentions to delay retirement, specifically related to socioeconomic indicators such as individual earnings, amount of debt, level of education, and parents' level of education. The differences between the groups were primarily influenced by the amount of debt, having a defined benefit plan, and parents' level of education, reflecting the cumulative disadvantage experienced by Hispanics over their life course. Conclusion: Most existing research on the topic has focused on middle-class Whites, while few studies have examined race or ethnicity as the primary focus or explored the extent to which commonly identified predictors of delayed retirement apply to different ethno-racial groups. This is significant because Hispanics and other disadvantaged groups tend to experience financial insecurity during retirement, which directly impacts their health and well-being.

Is time of eating associated with BMI and obesity? A population-based study.

PURPOSE: Time-related eating patterns have been associated with metabolic and nutritional diseases such as obesity. However, there is a lack of representative studies on this subject. This study's aim was to assess the association between the timing of eating and obesity in a large and representative sample of the Brazilian adult population (POF 2008-2009 survey). METHODS: Two days of adults' food diary (n = 21,020) were used to estimate tertiles of first and last meal intake times, eating midpoint, caloric midpoint time, and calories consumed from 18:00 h onwards. BMI was estimated and its values, as well as excess weight (BMI ≥ 25 kg/m2) and obesity (BMI ≥ 30 kg/m2) were used as outcomes. Multiple linear and logistic regressions were performed. RESULTS: The first (ß = 0.65, 95% CI 0.37-0.93) and last food intake time (ß = 0.40, 95% CI 0.14-0.66), eating midpoint (ß = 0.61, 95% CI 0.34-0.88) and calories consumed after 21:00 h (ß = 0.74, 95% CI 0.32-1.16) and 22:00 h (ß = 0.75, 95% CI 0.18-1.32) were positively associated with BMI. The likelihood of having excess weight or obesity was significantly higher in the third tertile of the first food intake time (OR = 1.28, 95% CI 1.13-1.45 and OR = 1.34, 95% CI 1.13-1.58, respectively), last food intake time (OR = 1.16, 95% CI 1.03-1.32; and OR = 1.18, 95% CI 1.00-1.41, respectively), eating midpoint (OR = 1.28, 95% CI 1.13-1.45; and OR = 1.35, 95% CI 1.14-1.59, respectively) and energy consumption after 21:00 h (OR = 1.33, 95% CI 1.10-1.59). CONCLUSION: Chrononutrition meal patterns indicative of late meal intake were significantly associated with high BMI, excess weight and obesity in the Brazilian population.

Parapharyngeal and retropharyngeal infections in children: Kawasaki disease needs vigilance

Abstract Objective Kawasaki Disease (KD) may mimic Parapharyngeal (PPI) and Retropharyngeal Infections (RPI), leading to misdiagnosis as Deep Neck Infections (DNIs). The treatment plans for the two diseases are different, and delayed treatment can lead to serious complications. Therefore, prompt diagnosis and management are necessary. This study was performed to evaluate the clinical features of KD mimicking DNIs and explore the treatment options. Methods Children with cellulitis or abscess in parapharyngeal or retropharyngeal space in neck CT were included in this study. The medical records of enrolled children were retrospectively reviewed. Results In total, 56 children were diagnosed with PPI or/and RPI. Twenty-two (39.3%) participants were eventually diagnosed with KD, and 34 (60.7%) were diagnosed with DNIs. Compared with the DNIs group, the KD group had a higher body temperature (p = 0.007), and higher levels of AST (p = 0.040), ALT (p = 0.027), and ESR (p = 0.030). Deep cervical cellulitis (p = 0.005) were more common in the KD group. However, deep neck abscess often occurred in the DNIs group (p = 0.002), with parapharyngeal abscess being the most common type of abscess (p = 0.004). The KD mimicking DNIs cases did not respond to antibiotic treatment, but symptoms significantly improved after the use of Immunoglobulin (IVIG) and aspirin. Conclusion Children with KD may exhibit retropharyngeal or parapharyngeal inflammation in the early stages. KD should be considered a differential diagnosis for children with DNIs, high fever, and no response to antibiotic therapy. Surgery in KD mimicking deep neck abscess requires caution. Level of Evidence I.

Is evening chronotype associated with higher alcohol consumption? A systematic review and meta-analysis.

A broader understanding of whether and to what extent chronotype should be considered a risk factor for alcohol consumption is needed. The aim of this systematic review was to summarize the evidence on the association between evening chronotype and alcohol consumption. A systematic search of observational studies on this association was conducted in the PubMed, Scopus, Web of Science, Cochrane Library and PsycINFO databases up to April 30th, 2023. Random-effect models estimated the pooled odds ratio (OR) of alcohol consumption according to chronotype. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Quality Assessment tool for Observational Cohorts and Cross-sectional Studies from the National Heart, Lung and Blood Institute were followed. A total of 33 studies involving 28 207 individuals (age range: 18-93 years) were included in this review. Overall, most studies indicated a higher volume and frequency of alcohol consumption in evening-type individuals than in individuals with different chronotypes. Additionally, a meta-analysis including 13 studies showed that evening-type individuals were 41% more likely to consume alcohol than those with other chronotypes (OR = 1.41, 95% confidence interval: 1.16-1.66; I2 = 38.0%). Limitations of the present findings are the predominance of cross-sectional studies and varied definitions of alcohol consumption. The available evidence supports an association between the evening chronotype and alcohol consumption. The evening-type population, especially young adults, is a specific target for educational interventions for preventing or reducing alcohol consumption.PROSPERO number: CRD42022343778.

Familial central precocious puberty due to DLK1 deficiency: novel genetic findings and relevance of serum DLK1 levels.

BACKGROUND: Several rare loss-of-function mutations of delta-like noncanonical notch ligand 1 (DLK1) have been described in non-syndromic children with familial central precocious puberty (CPP). OBJECTIVE: We investigated genetic abnormalities of DLK1 gene in a French cohort of children with idiopathic CPP. Additionally, we explored the pattern of DLK1 serum levels in patients with CPP and in healthy children at puberty, as well as in wild-type female mice. PATIENTS AND METHODS: Genomic DNA was obtained from 121 French index cases with CPP. Automated sequencing of the coding region of the DLK1 gene was performed in all cases. Serum DLK1 levels were measured by enzyme linked immunosorbent assay (ELISA) in 209 individuals, including 191 with normal pubertal development and in female mice during postnatal pubertal maturation. RESULTS: We identified 2 rare pathogenic DLK1 allelic variants: A stop gain variant (c.372C>A; p.Cys124X) and a start loss variant (c.2T>G; p.Met1?, or p.0) in 2 French girls with CPP. Mean serum DLK1 levels were similar between healthy children and idiopathic CPP children. In healthy individuals, DLK1 levels correlated with pubertal stage: In girls, DLK1 decreased between Tanner stages III and V, whereas in boys, DLK1 decreased between Tanner stages II and V (P = .008 and .016, respectively). Serum levels of Dlk1 also decreased in wild-type female mice. CONCLUSIONS: Novel loss-of-function mutations in DLK1 gene were identified in 2 French girls with CPP. Additionally, we demonstrated a pattern of dynamic changes in circulating DLK1 serum levels in humans and mice during pubertal stages, reinforcing the role of this factor in pubertal timing.

Late meal intake is associated with abdominal obesity and metabolic disorders related to metabolic syndrome: A chrononutrition approach using data from NHANES 2015-2018.

BACKGROUND & AIMS: Chrononutrition is an emerging area that suggests that late eating time is associated with poor nutritional and metabolic outcomes. However, epidemiological studies are scarce on this topic. The aim of this study was to characterize the chrononutrition patterns in a large and representative US population (NHANES 2015-2016 and 2017-2018) of adults and elderly and investigate their association with obesity and metabolic disorders that make up the metabolic syndrome. METHODS: A total of 7379 adults and elderly individuals were included in the analysis. Meal timing data were collected through two 24-h dietary recalls in both cycles. Poisson regression adjusted for confounders was used to evaluate the association between chrononutrition variables (eating duration and tertiles of first and last meal timing, eating midpoint and eating occasions) and obesity, abdominal obesity and metabolic parameters from metabolic syndrome. RESULTS: Adults with a longer eating duration (>12 h) had a higher prevalence of abdominal obesity (IRR, 1.15; 95% CI, 1.03-1.28) when compared with those who ate their meals in a shorter eating duration (≤12 h). In addition, adults in the third tertile of the time of the last meal (mean 22:03) had a higher prevalence of abdominal obesity (IRR, 1.12; 95% CI, 1.01-1.25) compared to first tertile. Adults with later eating midpoints (second and third tertile) had a higher prevalence of elevated fasting glucose (IRR, 1.30; 95% CI, 1.07-1.59 and IRR, 1.65; 95% CI, 1.22-2.22, respectively). Among the elderly, participants with a longer eating duration (>12 h) had a higher prevalence of elevated triglycerides (IRR, 2.74; 95% CI, 1.25-5.96) when compared with those elderly who ate their meals in a shorter eating duration (≤12 h). CONCLUSION: These findings suggest that a long eating duration and late first and last meal timing are chrononutrition patterns associated with cardiometabolic risks in free-living Americans.

Performance Analysis of Orthogonal Multiplexing Techniques for PLC Systems with Low Cyclic Prefix Length and Symbol Timing Offset.

This paper investigates the degradation caused by interference resulting from cyclic prefix violation and symbol timing offset in narrowband power line communication systems. In this sense, it presents a unified formulation from which Hermitian symmetric orthogonal frequency division multiplexing (HS-OFDM), orthogonal chirp division multiplexing (OCDM), single-carrier cyclic prefix (SCCP), and orthogonal time-frequency division multiplexing (OTFDM) can be easily derived. The paper then provides closed-form expressions for quantifying the aforementioned interference in the presence of a frequency domain equalizer. The numerical analyses exhibit the performances of these schemes under various data communication conditions, such as the availability of channel state information, the presence or absence of interference, modeling of additive noise as a white or colored Gaussian random process, frequency domain equalizer type, and the use of bit and power allocation techniques. The closed-form expressions and performance analyses regarding achievable data rate and bit error probability provide guidance for dealing with distinct constraints in narrowband power line communication (PLC) systems using the HS-OFDM, OCDM, SCCP, or OTFDM scheme. Lastly, the unified formulation and results obtained motivate the design of multi-scheme transceivers.

Replication Timing Aberration of KIF14 and MDM4 / PI3KC 2 ß Alleles and Aneuploidy as Markers of Chromosomal Instability and Poor Treatment Response in Ewing Family Tumor Patients.

Replication timing of allelic gene pairs is strictly regulated according to expression, genome stability, and epigenetic changes, and tumorigenesis may be associated with changes in the allelic replication in various tumors. Our aim was to determine whether such alterations had a prognostic value in Ewing's family tumor (EFT) patients. The KIF14 and MDM4 / PI3KC 2ß and the centromeric satellite sequence of chromosomes 8 and 12 were used for replication timing assessments. Aneuploidy was assessed by enumerating the copy numbers of chromosomes 8 and 12. Replication timing and aneuploidy were detected cytogenetically using multicolors fluorescence in situ hybridization assay applied in 135 EFT. Patients with trisomy 8 presented an association with an asynchronous replication pattern (SD) of MDM4 / PI3KC 2ß genes ( p = 0.013). Trisomy 12 was associated with a synchronous pattern (DD) of KIF14 probe signals ( p = 0.04). The DD synchronous replication pattern of KIF14 showed a correlation with age ( p < 0.0001), and the SS synchronous replication pattern of the same locus showed a correlation with lung metastatic ( p = 0.012). The subgroup of patients presenting with multiplet signals of MDM4 / PI3KC 2ß showed an association with treatment response ( p = 0.045) and age ( p = 0.033). Replication pattern of KIF14 may, significantly, be associated with chromosomal instability as MDM4 / PI3KC 2ß may be a considerably new marker of poor treatment response in EFT patients.

Time perception and pain: Can a temporal illusion reduce the intensity of pain?

It is commonly known-and previous studies have indicated-that time appears to last longer during unpleasant situations. This study examined whether a reciprocal statement can be made-that is, whether changes in the perception of time can influence our judgment (or rating) of a negative event. We used a temporal illusion method (Pomares et al. Pain 152, 230-234, 2011) to induce distortions in the perception of time. Two stimuli were presented for a constant time: a full clock, which stayed on the screen until its clock hand completed a full rotation (360°); and a short clock, in which the clock hand moved just three-quarters of the way (270°), thus suggesting a reduced interval duration. However, both stimuli were shown for the same amount of time. We specifically investigated (a) whether we could induce a temporal illusion with this simple visual manipulation, and (b) whether this illusion could change participants' ratings of a painful stimulus. In Experiment I (n = 22), to answer (a) above, participants were asked to reproduce the duration in which the different clocks were presented. In Experiment II (n = 30), a painful thermal stimulation was applied on participants' hands while the clocks were shown. Participants were asked to rate the perceived intensity of their pain, and to reproduce its duration. Results showed that, for both experiments, participants reproduced a longer interval after watching the full clock compared with the short clock, confirming that the clock manipulation was able to induce a temporal illusion. Furthermore, the second experiment showed that participants rated the thermal stimuli as less painful when delivered with the short clock than with the full clock. These findings suggest that temporal distortions can modulate the experience of pain.