Prior expectations facilitate metacognition for perceptual decision.

The influential framework of 'predictive processing' suggests that prior probabilistic expectations influence, or even constitute, perceptual contents. This notion is evidenced by the facilitation of low-level perceptual processing by expectations. However, whether expectations can facilitate high-level components of perception remains unclear. We addressed this question by considering the influence of expectations on perceptual metacognition. To isolate the effects of expectation from those of attention we used a novel factorial design: expectation was manipulated by changing the probability that a Gabor target would be presented; attention was manipulated by instructing participants to perform or ignore a concurrent visual search task. We found that, independently of attention, metacognition improved when yes/no responses were congruent with expectations of target presence/absence. Results were modeled under a novel Bayesian signal detection theoretic framework which integrates bottom-up signal propagation with top-down influences, to provide a unified description of the mechanisms underlying perceptual decision and metacognition.

Light Sensitive Liposomes: A Novel Strategy for Targeted Drug Delivery.

Light-sensitive liposomes have emerged as a promising platform for drug delivery, offering the potential for precise control over drug release and targeted therapy. These lipid-based nanoparticles possess photoresponsive properties, allowing them to undergo structural changes or release therapeutic payloads upon exposure to specific wavelengths of light. This review presents an overview of the design principles, fabrication methods, and applications of light-sensitive liposomes in drug delivery. Further, this article also discusses the incorporation of light-sensitive moieties, such as azobenzene, spiropyran, and diarylethene, into liposomal structures, enabling spatiotemporal control over drug release. The utilization of photosensitizers and imaging agents to enhance the functionality and versatility of light-sensitive liposomes is also highlighted. Finally, the recent advances, challenges, and future directions in the field, emphasizing the potential for these innovative nanocarriers to revolutionize targeted therapeutics, are also discussed.

Dynamical independence: Discovering emergent macroscopic processes in complex dynamical systems.

We introduce a notion of emergence for macroscopic variables associated with highly multivariate microscopic dynamical processes. Dynamical independence instantiates the intuition of an emergent macroscopic process as one possessing the characteristics of a dynamical system "in its own right," with its own dynamical laws distinct from those of the underlying microscopic dynamics. We quantify (departure from) dynamical independence by a transformation-invariant Shannon information-based measure of dynamical dependence. We emphasize the data-driven discovery of dynamically independent macroscopic variables, and introduce the idea of a multiscale "emergence portrait" for complex systems. We show how dynamical dependence may be computed explicitly for linear systems in both time and frequency domains, facilitating discovery of emergent phenomena across spatiotemporal scales, and outline application of the linear operationalization to inference of emergence portraits for neural systems from neurophysiological time-series data. We discuss dynamical independence for discrete- and continuous-time deterministic dynamics, with potential application to Hamiltonian mechanics and classical complex systems such as flocking and cellular automata.

A study on knowledge, beliefs and attitude towards leprosy in students of Jaipur, Rajasthan.

The objective of this study was to determine the knowledge, beliefs and attitudes regarding leprosy in school students of Jaipur district. A cross-sectional study was conducted from August 2010 to February 2011 on 1199 students (rural and urban) studying in class 10th and above. The findings of this study showed fair knowledge in students about cause, signs and symptoms of leprosy but less knowledge about prevention and treatment of the disease. Myths and beliefs were more prevalent in rural students as compared to urban ones. Both the groups showed positive attitude toward leprosy with 30-50% students showing neutral approach but negative reaction was more in rural students. In conclusion the study highlights to emphasize on health education in students and improving knowledge to develop positive attitude towards leprosy.

Modes and models in disorders of consciousness science.

The clinical assessment of non-communicative brain damaged patients is extremely difficult and there is a need for paraclinical diagnostic markers of the level of consciousness. In the last few years, progress within neuroimaging has led to a growing body of studies investigating vegetative state and minimally conscious state patients, which can be classified in two main approaches. Active neuroimaging paradigms search for a response to command without requiring a motor response. Passive neuroimaging paradigms investigate spontaneous brain activity and brain responses to external stimuli and aim at identifying neural correlates of consciousness. Other passive paradigms eschew neuroimaging in favour of behavioural markers which reliably distinguish conscious and unconscious conditions in healthy controls. In order to furnish accurate diagnostic criteria, a mechanistic explanation of how the brain gives rise to consciousness seems desirable. Mechanistic and theoretical approaches could also ultimately lead to a unification of passive and active paradigms in a coherent diagnostic approach. In this paper, we survey current passive and active paradigms available for diagnosis of residual consciousness in vegetative state and minimally conscious patients. We then review the current main theories of consciousness and see how they can apply in this context. Finally, we discuss some avenues for future research in this domain.

Hypothesis awareness confounds asynchronous control conditions in indirect measures of the rubber hand illusion.

Reports of changes in experiences of body location and ownership following synchronous tactile and visual stimulation of fake and real hands (rubber hand (RH) effects) are widely attributed to multisensory integration mechanisms. However, existing control methods for subjective report measures (asynchronous stroking and control statements) are confounded by participant hypothesis awareness; the report may reflect response to demand characteristics. Subjective report is often accompanied by indirect (also called 'objective' or 'implicit') measures. Here, we report tests of expectancies for synchronous 'illusion' and asynchronous 'control' conditions across two pre-registered studies (n = 140 and n = 45) for two indirect measures: proprioceptive drift (a change in perceived hand location) and skin conductance response (a measure of physiological arousal). Expectancies for synchronous condition measures were greater than for asynchronous conditions in both studies. Differences between synchronous and asynchronous control condition measures are therefore confounded by hypothesis awareness. This means indirect measures of RH effects may reflect compliance, bias and phenomenological control in response to demand characteristics, just as for subjective measures. Valid control measures are required to support claims of a role of multisensory integration for both direct and indirect measures of RH effects.

Trait phenomenological control predicts experience of mirror synaesthesia and the rubber hand illusion.

In hypnotic responding, expectancies arising from imaginative suggestion drive striking experiential changes (e.g., hallucinations) - which are experienced as involuntary - according to a normally distributed and stable trait ability (hypnotisability). Such experiences can be triggered by implicit suggestion and occur outside the hypnotic context. In large sample studies (of 156, 404 and 353 participants), we report substantial relationships between hypnotisability and experimental measures of experiential change in mirror-sensory synaesthesia and the rubber hand illusion comparable to relationships between hypnotisability and individual hypnosis scale items. The control of phenomenology to meet expectancies arising from perceived task requirements can account for experiential change in psychological experiments.

Conscious perception and the modulatory role of dopamine: no effect of the dopamine D2 agonist cabergoline on visual masking, the attentional blink, and probabilistic discrimination.

RATIONALE: Conscious perception is thought to depend on global amplification of sensory input. In recent years, striatal dopamine has been proposed to be involved in gating information and conscious access, due to its modulatory influence on thalamocortical connectivity. OBJECTIVES: Since much of the evidence that implicates striatal dopamine is correlational, we conducted a double-blind crossover pharmacological study in which we administered cabergoline-a dopamine D2 agonist-and placebo to 30 healthy participants. Under both conditions, we subjected participants to several well-established experimental conscious-perception paradigms, such as backward masking and the attentional blink task. RESULTS: We found no evidence in support of an effect of cabergoline on conscious perception: key behavioral and event-related potential (ERP) findings associated with each of these tasks were unaffected by cabergoline. CONCLUSIONS: Our results cast doubt on a causal role for dopamine in visual perception. It remains an open possibility that dopamine has causal effects in other tasks, perhaps where perceptual uncertainty is more prominent.

Auxin and kinetin interaction in apical dominance.

The effects of auxin on the inhibition of lateral buds in decapitated bean plants are enhanced if kinetin is applied together with auxin. The uptake of (14)C-indoleacetic acid by the stumps of decapitated plants is increased in the presence of kinetin and leads to extensive transport of (14)C-indoleacetic acid in the stems. The increased bud inhibition resulting when auxin and kinetin are applied together may be due to greater amounts of auxin reaching the buds, but an alternative explanation is that metabolites are directed from the buds to the point of hormone application.

Auxin effects on the mobility of kinetin in the plant.

Kinetin (6-furfurylaminopurine) is generally considered to be relatively immobile within plants. Kinetin labeled with (14)C was applied to the stumps of decapitated bean plants, with or without simultaneous application of indoleacetic acid. Significantly greater amounts of kinetin moved downwards in the stem in the presence of added indoleacetic acid than in its absence.

Requirement of ets-2 expression for Xenopus oocyte maturation.

A molecular clone of the Xenopus laevis ets-2 gene was isolated from an oocyte complementary DNA library. The amount of messenger RNA (mRNA) in each oocyte or embryo was almost constant during oogenesis and was maintained until the blastula stage of embryonic development, indicating that the observed 3.2-kilobase transcript is a maternal message. The only normal adult tissue in which ets-2 mRNA was detected was the ovary. Injection of antisense oligonucleotides homologous to the ets-2 sequence into oocytes led to degradation of the mRNA and blocked hormone-induced germinal vesicle breakdown. The ets-2 product is thus required for the meiotic maturation of Xenopus oocytes.

Epidemiological and clinical profile of irritable bowel syndrome in India: report of the Indian Society of Gastroenterology Task Force.

AIMS: To study the profile of irritable bowel syndrome (IBS), and the frequency of such symptoms among the general population, in India. METHODS: In this prospective, multi-center study, data were obtained from 2785 patients with chronic lower gastrointestinal symptoms (complainants) with no alarm feature and negative investigations for organic causes visiting physicians at 30 centers, and from 4500 community subjects (non-complainants), using separate questionnaires. RESULTS: Most complainants were middle-aged (mean age 39.4 years) and male (1891; 68%). The common symptoms were: abdominal pain or discomfort (1958; 70%), abdominal fullness (1951; 70%); subjective feeling of constipation (1404 of 2656; 53%), or diarrhea (1252 of 2656, 47%), incomplete evacuation (2134; 77%), mucus with stools (1506; 54%), straining at stools (1271; 46%), epigastric pain (1364; 49%) and milk intolerance (906; 32%). Median stool frequency was similar in patients who felt they had constipation or those who felt they had diarrhea. Information to subtype symptoms using standard criteria was available in 1301 patients; of these, 507 (39%) had constipation-predominant IBS ( 3 3 stools/day) and 744 (57%) had indeterminate symptoms. Among non-complainants, most subjects reported daily defecation frequency of one (2520 [56%]) or two (1535 [34%]). Among non-complainants, 567 (12.6%) reported abdominal pain, 503 (11%) irregular bowel, 1030 (23%) incomplete evacuation, 167 (4%) mucus and 846 (18%) straining at stools; a combination of abdominal pain or discomfort relieved by defecation, and incomplete evacuation was present in 189/4500 (4.2%) community subjects. CONCLUSIONS: Most patients with IBS in India are middle-aged men, and have a sense of incomplete evacuation and mucus with stools. Abdominal pain or discomfort is frequent but not universal. Importantly, stool frequency was similar irrespective of whether the patients felt having constipation or diarrhea. Most (90%) non-complainant subjects had 1 or 2 stools per day; symptoms complex suggestive of IBS was present in 4.2% of community subjects.

Protein-c deficiency presenting with subacute intestinal obstruction due to mesenteric vein thrombosis.

We describe a patient with protein C deficiency who presented with subacute intestinal obstruction due to ischaemic small bowel stricture. The patient also had left sided ileofemoral thrombosis. Venous thrombosis at unusual sites especially if associated with deep vein thrombosis of lower limb warrants a thorough screen for underlying thrombophilia. This, however, is a rare cause for ischaemic small bowel stricture.

Risk Factors of Hepatotoxicity During Anti-tuberculosis Treatment.

BACKGROUND: Antituberculosis treatment (ATT) induced hepato-toxicity is common, but risk factors predicting its development are poorly understood. The present study evaluates the clinical risk factors predicting the development of hepatotoxicity in Indian patients with tuberculosis on antituberculosis treatment. METHODS: Three groups of patients were studied at three service hospitals over a 3 year period from 2000-2002. Patients given ATT were followed up with monthly LFTs. Consecutive patients who developed Liver dysfunction (rise in SGPT > 5 times upper limit of normal) were studied, along with matched controls who did not. Markers for hepatitis B were also noted in these patients once in 6 months. A third group of patients who did not receive ATT but were HBsAg positive, were also similarly followed up. The possible association of age and sex of the patient, alcoholism, unrecognized chronic liver disease, hepatitis B virus carrier status and nutritional status with ATT-induced hepatitis was assessed. Statistical analysis was carried out by Chi square test/Fisher's exact test using WHO provided software Epi Info 6. Sixty-nine patients with ATT-induced hepatotoxicity were prospectively studied. In addition 128 patients on anti-tuberculosis drugs without hepatotoxicity and 39 HBsAg carriers not on ATT were followed up for 1 year. RESULTS: Age, Sex, history of alcohol intake and BMI were not found to be related to development of hepatotoxicity. Presence of HBV infection or an underlying silent chronic liver disease were found to significantly increase the risk of development of ATT-induced hepatotoxicity. Continuation of ATT after development of jaundice was associated with a high fatality rate. It was possible to re-introduce isoniazid in 96% and rifampicin in 88% of patients with ATT induced hepatotoxicity. CONCLUSION: ATT-induced hepatitis is common and is potentially fatal. It is likely to occur in those with underlying silent chronic liver disease, HBV infection and have been given ATT without a definite evidence of tuberculosis. Discontinuation of ATT leads to rapid recovery in most cases and drugs can safely be introduced after recovery in a majority of cases.

A novel transcription factor, ELF5, belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13-15, a region subject to LOH and rearrangement in human carcinoma cell lines.

The ETS transcription factors are a large family implicated in the control of cellular proliferation and tumorigenesis. In addition, chromosomal translocations involving ETS family members are associated with a range of different human cancers. Given the extensive involvement of ETS factors in tumorigenesis, it becomes important to identify any additional ETS genes that may also play oncogenic roles. We identify a novel gene, ELF5, that appears to belong to the ELF (E74-like-factor) subfamily of the ETS transcription factor family, based upon similarity within the 'ETS domain'. ELF5 displays a similar, but more restricted, expression pattern to that of the newly isolated epithelium-specific ETS gene, ELF3. Unlike most other ETS family members, ELF5 is not expressed in hematopoietic compartments, but is restricted to organs such as lung, stomach, kidney, prostate, bladder and mammary gland. ELF5 is localized to human chromosome 11p13-15, a region that frequently undergoes loss of heterozygosity (LOH) in several types of carcinoma, including those of breast, kidney and prostate. We find that ELF5 expression is not detectable in a number of carcinoma cell lines, some of which display loss or rearrangement of an ELF5 allele. Similar to other ETS family members, ELF5 displays specific binding to DNA sequences containing a GGAA-core. In addition, ELF5 is able to transactivate through these ETS sequences, present upstream from a minimal promoter. Our data suggest that ELF5 may play roles in mammary, lung, prostate and/or kidney function, and possibly also in tumorigenesis.

A comparative study of electrical potential sensors and Ag/AgCl electrodes for characterising spontaneous and event related electroencephalagram signals.

BACKGROUND: Electroencephalography (EEG) is still a widely used imaging tool that combines high temporal resolution with a relatively low cost. Ag/AgCl metal electrodes have been the gold standard for non-invasively monitoring electrical brain activity. Although reliable, these electrodes have multiple drawbacks: they suffer from noise, such as offset potential drift, and usability issues, for example, difficult skin preparation and cross-coupling of adjacent electrodes. NEW METHOD: In order to tackle these issues a prototype Electric Potential Sensor (EPS) device based on an auto-zero operational amplifier was developed and evaluated. The EPS is a novel active ultrahigh impedance capacitively coupled sensor. The absence of 1/f noise makes the EPS ideal for use with signal frequencies of ∼10Hz or less. A comprehensive study was undertaken to compare neural signals recorded by the EPS with a standard commercial EEG system. RESULTS: Quantitatively, highly similar signals were observed between the EPS and EEG sensors for both free running and evoked brain activity with cross correlations of higher than 0.9 between the EPS and a standard benchmark EEG system. COMPARISON WITH EXISTING METHOD(S): These studies comprised measurements of both free running EEG and Event Related Potentials (ERPs) from a commercial EEG system and EPS. CONCLUSIONS: The EPS provides a promising alternative with many added benefits compared to standard EEG sensors, including reduced setup time and elimination of sensor cross-coupling. In the future the scalability of the EPS will allow the implementation of a whole head ultra-dense EPS array.

Recurrent acute respiratory tract infections in areas with high nitrate concentrations in drinking water.

A review of the literature indicated an association among high nitrate ingestion, methemoglobinemia, and pathologic changes in bronchi and lung parenchyma. The present study examined a possible correlation among drinking water nitrate concentration, methemoglobin levels, cytochrome b(5) reductase activity, and acute respiratory tract infection with a history of recurrence (RRTI). Our study was conducted in five village units in the state of Rajasthan, India, with nitrate concentrations of 26, 45, 95, 222, and 459 mg NO(3) ion/L. We randomly selected 88 children. The children were up to 8 years of age, age matched, and represented 10% of the total population of these areas. We obtained detailed RRTI histories and conducted medical examinations. Methemoglobin levels and cytochrome b(5) reductase activity were estimated biochemically. The data collected were statistically analyzed using spreadsheet software on a personal computer. We observed strong interdependence between methemoglobin levels and RRTI in children up to 8 years of age. Methemoglobin levels alone explained 80% of the variation in the RRTI cases. This study indicates that methemoglobinemia, secondary to high nitrate ingestion in drinking water, causes RRTI. Increased production of methemoglobin and free radicals of nitric oxide and oxygen due to nitrate metabolism in the body lead to alveolar damage and mismatching of ventilation and perfusion, which may be the reason for high mortality in children due to RRTI.

Biomechanical analysis of flat and oblique tibial tubercle osteotomy for recurrent patellar instability.

Both flat (Elmslie-Trillat) and oblique (Fulkerson) osteotomy techniques are successful in treating patellar instability episodes by moving the tibial tubercle medially. The oblique osteotomy also results in anterior displacement that decreases patellofemoral forces. Recent reports have described proximal tibial fractures occurring during early weightbearing after oblique osteotomy. We performed oblique and flat osteotomies on 13 pairs of fresh-frozen cadaveric knees. The knees were then tested to failure on a materials testing system by exerting a load through the quadriceps tendon at a rate of 1000 N/sec to simulate a stumble injury. The failure mechanism for flat osteotomies was more likely to be tubercle "shingle" fracture, while oblique osteotomies more frequently failed through a tibial fracture or fixation failure in the posterior tibial cortex. Mean load to failure was significantly higher in the flat osteotomy specimens (1639 N versus 1166 N), as was total energy to failure (224 N.m versus 127 N.m). There was no significant difference in stiffness (87 N/cm versus 74 N/cm). We recommend the flat osteotomy for patients with isolated recurrent patellar instability and the oblique osteotomy in patients who have concomitant patellofemoral pain or articular degenerative changes. When an oblique osteotomy is used, we recommend postoperative brace protection and restricted weightbearing until the osteotomy heals.

Methaemoglobinaemia in areas with high nitrate concentration in drinking water.

BACKGROUND: An epidemiological investigation was undertaken in all age groups to assess the prevalence of methaemoglobinaemia in areas with high nitrate concentration in drinking water. METHODS: Five areas were selected with an average nitrate concentration (as nitrate) of 26, 45, 95, 222 and 459 mg nitrate ions/litre in drinking water. These areas were visited and the house schedule (containing name, age, sex and weight of the family members) prepared in accordance with the statistically designed protocol. In all, 178 persons, matched for age and weight, were selected and arranged in five age groups. They constituted 10% of the total population of each of these areas. A detailed history of the selected population was taken, medical examination conducted and blood samples taken to ascertain the level of methaemoglobin. The collected data were subjected to statistical analysis to ascertain a relationship between nitrate concentration and methaemoglobinaemia. RESULTS: High nitrate concentrations cause severe methaemoglobinaemia (7%-27% of Hb) in all age groups, especially in the age group of less than 1 year and above 18 years. The lower levels of methaemoglobin in the age group of 1-18 years is probably due to better reserve of cytochrome b5 reductase activity and its adaptation to increasing nitrate concentration in water to compensate for methaemoglobinaemia in this age group. CONCLUSION: We conclude that high nitrate ingestion causes methaemoglobinaemia in all age groups. Cytochrome b5 reductase activity and its adaptation with increasing water nitrate ingestion plays a role in compensating for the methaemoglobinaemia.