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Two main hypotheses regarding the directional flow of visual information processing in the brain have been proposed: feed-forward (bottom-up) and re-entrant (top-down). Early theories espoused feed-forward principles in which processing was said to advance from simple to increasingly complex attributes terminating at a higher area where conscious perceptions occur. That view is disconfirmed by advances in neuroanatomy and neurophysiology, which implicate re-entrant two-way signaling as the predominant form of communication between brain regions. With some notable exceptions, the notion of re-entrant processing has had a relatively modest effect on computational models of perception and cognition, which continue to be predominantly based on feed-forward or within-level re-entrant principles. In the present work we describe five sets of empirical findings that defy interpretation in terms of feed-forward or within-level re-entrant principles. We conclude by urging the adoption of psychophysical, biological, and computational models based on cross-level iterative re-entrant principles.

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Background: In a neonatal intensive care unit, streaming healthcare data comes from many sources, but humans are unable to understand relationships between data variables. Data mining and analysis are just beginning to get utilized in critical care. We present a case study using electronic medical record data in the neonatal intensive care unit and explore possible avenues of advancement using temporal data analytics. Case Presentation: Electronic medical record data were collected for physiological monitor data. Heart rate, respiratory rate, oxygen saturation and temperature data were retrospectively analyzed by temporal data mining. Three premature babies were selected and data de-identified. The first case of a urinary tract infection showed nursing ability to synthesize data streams coming from a patient. For the second case of necrotizing enterocolitis, Temporal-Data-Mining analysis of combinations of clinical events based on deviations from the mean showed specific heuristic biomarkers related to events before discovery of necrotizing enterocolitis. Specific sequences 6-event and 5-event in length were identified with nursing unease at clinical deterioration, which were 100- and 87-times unlikely to occur randomly with 99.5% confidence. No such sequences were found in the rest of the 37 days for the second case and entire 133 days of stay in the third case of an uneventful premature baby. Conclusion: Temporal data mining is a possible clinical tool in providing useful information in the neonatal intensive care unit for diagnosis of adverse clinical occurrences such as necrotizing enterocolitis. There is the possibility of changing the clinical paradigm of episodic watchfulness to constant vigilance using real-time data gathering.

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Background: Obstructive sleep apnea (OSA) is reported in a high proportion of cardiac surgical patients, up to 73%. STOP-BANG is a validated questionnaire for screening of outpatients for OSA with high sensitivity. There is sparse literature from India regarding the prevalence of OSA in preoperative cardiovascular patients and the utility of screening tools. Aims: We sought to study the utility of the STOP-BANG questionnaire as a screening tool for OSA in cardiovascular patients validating it with ambulatory level 3 polysomnography. Materials and Methods: It was a prospective study where consecutive patients getting admitted for coronary artery bypass surgery (CABG) from August 2017-February 2019 were recruited. All the patients were screened with the STOP-BANG questionnaire. 53 patients underwent overnight level 3 polysomnography using Apnea-Link. Correlations were made between clinical symptoms, STOP-BANG score, and OSA severity, measured using Apnea hypopnea index (AHI). Results: We had 120 patients(103 males) with a mean age 60 years. Snoring was the most common sleep complaint. Our cohort had a high prevalence of vascular risk factors (DM 72.3%, hypertension 59.2%, dyslipidemia 60%) and 11.7% were obese (BMI >30). The median STOP-BANG score was 3 (IQR 2) with 83 having scores ≥3. Median AHI was 5.6 with AHI ≥5 in 28 patients and AHI 15 or above in 14 patients. Among the clinical parameters, arousals with respiratory difficulty at night, higher neck circumference, and tonsillar hypertrophy showed a significant association with PSG-proven OSA.STOP-BANG scores 3 or above had a sensitivity of 75% in predicting OSA. Conclusions: Our study shows that in cardiovascular patients less symptomatic for sleep complaints, the STOP-BANG questionnaire is a useful screening tool for OSA in outpatient settings. Among clinical parameters, airway narrowing and neck circumference can predict OSA.

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Congenital long QT syndrome (LQTS) is a rare cardiac condition characterized by abnormality of either sodium or potassium ion channels resulting in prolongation of QT interval and thereby predisposing to life-threatening arrhythmia. Once the syndrome is diagnosed, measures should be taken to avoid sudden cardiac death. We present a rare case of LQTS associated with patent ductus arteriosus in a child, and a unique approach was used in managing both conditions.

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Repeating patterns of precisely timed activity across a group of neurons (called frequent episodes) are indicative of networks in the underlying neural tissue. This letter develops statistical methods to determine functional connectivity among neurons based on nonoverlapping occurrences of episodes. We study the distribution of episode counts and develop a two-phase strategy for identifying functional connections. For the first phase, we develop statistical procedures that are used to screen all two-node episodes and identify possible functional connections (edges). For the second phase, we develop additional statistical procedures to prune the two-node episodes and remove false edges that can be attributed to chains or fan-out structures. The restriction to nonoverlapping occurrences makes the counting of all two-node episodes in phase 1 computationally efficient. The second (pruning) phase is critical since phase 1 can yield a large number of false connections. The scalability of the two-phase approach is examined through simulation. The method is then used to reconstruct the graph structure of observed neuronal networks, first from simulated data and then from recordings of cultured cortical neurons.

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Heart attack, or acute myocardial infarction (AMI), is a leading cause of death in the United States (U.S.). The most effective therapy for AMI is rapid revascularization: the mechanical opening of the clogged artery in the heart. Forty-four percent of patients with AMI who are admitted to a non-revascularization hospital in the U.S. are transferred to a hospital with that capacity. Yet, we know little about the process by which community hospitals complete these transfers, and why publicly available hospital quality data plays a small role in community hospitals' choice of transfer destinations. Therefore, we investigated how community hospital staff implement patient transfers and select destinations. We conducted a mixed methods study involving: interviews with staff at three community hospitals (n = 25) in a Midwestern state and analysis of U.S. national Medicare records for 1996-2006. Community hospitals in the U.S., including our field sites, typically had longstanding relationships with one key receiving hospital. Community hospitals addressed the need for rapid AMI patient transfers by routinizing the collective, interhospital work process. Routinization reduced staff uncertainty, coordinated their efforts and conserved their cognitive resources for patient care. While destination selection was nominally a physician role, the decision was routinized, such that staff immediately contacted a "usual" transfer destination upon AMI diagnosis. Transfer destination selection was primarily driven at an institutional level by organizational concerns and bed supply, rather than physician choice or patient preference. Transfer routinization emerged as a form of social order that invoked tradeoffs between process speed and efficiency and patient-centered, quality-driven decision making. We consider the implications of routinization and institutional imperatives for health policy, quality improvement and health informatics interventions.

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Most Americans are in Intensive Care Units (ICUs) at some point during their lives. There is wide variation in the outcome quality of ICUs and so, thousands of patients who die each year in ICUs may have survived if they were at the appropriate hospital. In spite of a policy agenda from IOM calling for effective transfer of patients to more capable hospitals to improve outcomes, there appear to be substantial inefficiencies in the existing system. In particular, patients recurrently transfer to secondary hospitals rather than to a most-preferred option. We present data mining schemes and significance tests to discover these inefficient cascades. We analyze critical care transfer data in Medicare across nearly 5,000 hospitals in the United States over 10 years and present evidence that these transfers to secondary hospitals repeatedly cascade across multiple transfers, and that some hospitals seem to be involved in many cascades.

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We consider the problem of detecting statistically significant sequential patterns in multineuronal spike trains. These patterns are characterized by ordered sequences of spikes from different neurons with specific delays between spikes. We have previously proposed a data-mining scheme to efficiently discover such patterns, which occur often enough in the data. Here we propose a method to determine the statistical significance of such repeating patterns. The novelty of our approach is that we use a compound null hypothesis that not only includes models of independent neurons but also models where neurons have weak dependencies. The strength of interaction among the neurons is represented in terms of certain pair-wise conditional probabilities. We specify our null hypothesis by putting an upper bound on all such conditional probabilities. We construct a probabilistic model that captures the counting process and use this to derive a test of significance for rejecting such a compound null hypothesis. The structure of our null hypothesis also allows us to rank-order different significant patterns. We illustrate the effectiveness of our approach using spike trains generated with a simulator.

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Sequential firings with fixed time delays are frequently observed in simultaneous recordings from multiple neurons. Such temporal patterns are potentially indicative of underlying microcircuits and it is important to know when a repeatedly occurring pattern is statistically significant. These sequences are typically identified through correlation counts. In this paper we present a method for assessing the significance of such correlations. We specify the null hypothesis in terms of a bound on the conditional probabilities that characterize the influence of one neuron on another. This method of testing significance is more general than the currently available methods since under our null hypothesis we do not assume that the spiking processes of different neurons are independent. The structure of our null hypothesis also allows us to rank order the detected patterns. We demonstrate our method on simulated spike trains.

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SETTING: Bangalore City, India. OBJECTIVES: To assess the socio-economic profile, health-seeking behaviour and costs related to tuberculosis (TB) diagnosis and treatment among patients treated under the Revised National TB Control Programme (RNTCP). DESIGN: All 1106 new TB patients registered for treatment under the RNTCP in the second quarter of 2005 participated. Interviews at the beginning and at the end of treatment were conducted. A convenience sample of 32 patients treated outside the RNTCP also participated. RESULTS: Among the TB patients, respectively 50% and 39% were from low and middle standard of living (SL) households, and 77% were from households with a per capita income of less than US$1 per day. The first health contact was with a private practitioner in the case of >70% of patients. Mean patient delay was low, at 21 days, but the mean health system delay was 52 days. The average cost incurred by patients before treatment in the RNTCP was US$145, and during treatment it was US$21. Costs as a proportion of annual household income per capita were 53% for people from low SL households and 41% for those from other households. Costs during treatment faced by patients treated outside the RNTCP averaged US$127. CONCLUSION: Patients treated under the RNTCP through a public-private mix approach were predominantly poor. Many of them experienced considerable health expenditures before starting treatment. Additional efforts are required to reduce the delays and the number of health care providers consulted, and to ensure that patients are shifted to subsidised treatment within the RNTCP.

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SETTING: Bangalore City, India. OBJECTIVES: To assess the cost and cost-effectiveness of public-private mix (PPM) for tuberculosis (TB) care and control when implemented on a large scale. DESIGN: DOTS implementation under the Revised National TB Control Programme (RNTCP) began in 1999, PPM was introduced in mid-2001 and a second phase of intensified PPM began in 2003. Data on the costs and effects of TB treatment from 1999 to 2005 were collected and used to compare the two distinct phases of PPM with a scenario of no PPM. Costs were assessed in 2005 $US for public and private providers, patients and patient attendants. Sources of data included expenditure records, medical records, interviews with staff and patient surveys. Effectiveness was measured as the number of cases successfully treated. RESULTS: When PPM was implemented, total provider costs increased in proportion to the number of successfully treated TB cases. The average cost per patient treated from the provider perspective when PPM was implemented was stable, at US$69, in the intensified phase compared with US$71 pre-PPM. PPM resulted in the shift of an estimated 7200 patients from non-DOTS to DOTS treatment over 5 years. PPM implementation substantially reduced costs to patients, such that the average societal cost per patient successfully treated fell from US$154 to US$132 in the 4 years following the initiation of PPM. CONCLUSION: Implementation of PPM on a large scale in an urban setting can be cost-effective, and considerably reduces the financial burden of TB for patients.

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Capnography waveforms and capnometry are useful perioperative monitoring tools. The paramagnetic oxygen analyzers incorporated in many clinical monitoring systems estimate oxygen concentration in the breathing circuit during various phases of ventilation. The oxygen concentration is plotted as a real-time waveform and displayed as an oxygraph. However, the clinical utility of oxygraphy is under evaluated. We are reporting four different clinical scenarios in neurosurgical patients, wherein the information yielded by oxygraphy were either not available on the capnograph or were revealed in a more promising way on the oxygraph than on the capnograph. A real-time oxygraphy waveform has four phases similar to a capnograph, although displayed in a reverse manner. Oxygraphy was useful in our patient to determine the adequacy of preoxygenation. Airway complications and unwanted neuromuscular recovery can be detected earlier by oxygraphy compared to capnography. The oxygraphy peak-to-baseline scale difference can be compressed to as low as to 6% of oxygen concentration. When the peak-to-baseline scale difference is 6 mmHg, the oxygraph becomes sensitive to even minute changes in respiratory flow characteristics. Oxygraphy may have a potential role in clinical monitoring.

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Atrial septal defect is usually closed in the cardiac catheterisation laboratory using atrial septal occluder (ASO) device. One of the complications associated with the procedure is embolisation of the device into the pulmonary artery. We are reporting two cases wherein the pulmonary embolisation of ASO device occurred during the procedure in one patient and in the early post-procedure period in another; both were retrieved surgically. We are also describing the haemodynamic consequences of this complication and the role of intraoperative transoesophageal echocardiography during surgical retrieval of the device.

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A high-performance liquid chromatographic method for the estimation of berberine in the stem of Tinospora cordifolia (Willd.) Miers. ex Hook.f. and Thoms. and Tinospora sinensis (Lour.) Merrill is described. The dried stems of T. cordifolia and T. sinensis were defatted with petroleum ether (60-80 degrees ). The marc was dried and further extracted with methanol. The concentration of berberine in methanol extract was determined using a C-18 reverse phase column with a mobile phase of acetonitrile:water (10:90 v/v) at a flow rate of 0.6 ml/min and with UV detection at 266 nm. TLC and HPLC comparison of both the species revealed significant variation in the chemical constitution of the two species. This observation becomes important in the context of the use of T. sinensis in place of the genuine drug T. cordifolia.

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A reverse phase HPLC method with UV detection has been developed and validated in order to quantify plumbagin, the bioactive marker of the roots of P. indica and P. zeylanica. A quantitative HPTLC method was also developed using hexane: ethyl acetate (8:2) as the mobile phase. The plumbagin content in the roots were determined using both the methods. P. indica was found to contain significantly higher amount of plumbagin than P. zeylanica. The HPLC and HPTLC methods described here are simple, rapid, accurate and sensitive.

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SETTING: Twenty-six selected districts in India. OBJECTIVES: To estimate the average annual risk of tuberculous infection (ARTI) in four defined zones in the country. STUDY DESIGN: A tuberculin survey was conducted in selected clusters of 26 districts in four defined zones of India. Children 1-9 years of age were subjected to tuberculin testing with ITU PPD RT23 with Tween 80, and the maximum transverse diameter of induration was measured 72 h later. Prevalence of infection was estimated using the cut-off point method (Method I) and the mirror-image technique (Method II) among children without bacille Calmette-Guérin scar. Results from individual zones have been reported earlier, and the results from all four zones are presented here as a consolidated summary. RESULTS: The ARTI computed from estimated prevalence was found to be lowest in the southern zone (Method I: 1.1%, Method II: 1.0%). It was higher in the eastern zone (1.3% by both methods) and highest in the western (Method I: 1.8%, Method II: 1.6%) and northern zones (1.9% by both methods). The proportion of infected children was found to be significantly higher in urban than in rural areas in all zones. CONCLUSION: The intensified tuberculosis control efforts need to be sustained for many years.

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Estimates of the prevalence of tuberculous infection among children 1-9 years of age were available for four defined zones of India from a recently concluded tuberculin survey. These were pooled together and the average annual risk of infection in the country was computed as 1.5%. It was higher in urban areas, at 2.2%, than in rural areas, at 1.3%. The results call for further intensification of tuberculosis control activities, especially in urban areas, greater involvement of private practitioners and information, education and communication (IEC) for high-risk groups, to reduce the diagnostic and treatment delay thereby reducing the transmission of infection in all settings.

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