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Sudhir Kumar

Publications and source records attributed to Sudhir Kumar.

At least 37 records · Page 2Linked to original sources

Pushing back the expansion of introns in animal genomes.

In a recent paper in Science, surveyed the position of introns in 30 genes of a marine annelid and showed that over 60% of the introns occupy positions identical to those in human homologs. In contrast, both human and marine annelid genes share only 30% of their introns with other invertebrates. These observations suggest that the common ancestor of most animal phyla had intron-rich genes and reinforce the notion that introns proliferated early in the evolutionary history of eukaryotes.

Animals↗

Placing confidence limits on the molecular age of the human-chimpanzee divergence.

Molecular clocks have been used to date the divergence of humans and chimpanzees for nearly four decades. Nonetheless, this date and its confidence interval remain to be firmly established. In an effort to generate a genomic view of the human-chimpanzee divergence, we have analyzed 167 nuclear protein-coding genes and built a reliable confidence interval around the calculated time by applying a multifactor bootstrap-resampling approach. Bayesian and maximum likelihood analyses of neutral DNA substitutions show that the human-chimpanzee divergence is close to 20% of the ape-Old World monkey (OWM) divergence. Therefore, the generally accepted range of 23.8-35 millions of years ago for the ape-OWM divergence yields a range of 4.98-7.02 millions of years ago for human-chimpanzee divergence. Thus, the older time estimates for the human-chimpanzee divergence, from molecular and paleontological studies, are unlikely to be correct. For a given the ape-OWM divergence time, the 95% confidence interval of the human-chimpanzee divergence ranges from -12% to 19% of the estimated time. Computer simulations suggest that the 95% confidence intervals obtained by using a multifactor bootstrap-resampling approach contain the true value with >95% probability, whether deviations from the molecular clock are random or correlated among lineages. Analyses revealed that the use of amino acid sequence differences is not optimal for dating human-chimpanzee divergence and that the inclusion of additional genes is unlikely to narrow the confidence interval significantly. We conclude that tests of hypotheses about the timing of human-chimpanzee divergence demand more precise fossil-based calibrations.

Animals↗

Maximum likelihood outperforms maximum parsimony even when evolutionary rates are heterotachous.

Heterotachy occurs when the relative evolutionary rates among sites are not the same across lineages. Sequence alignments are likely to exhibit heterotachy with varying severity because the intensity of purifying selection and adaptive forces at a given amino acid or DNA sequence position is unlikely to be the same in different species. In a recent study, the influence of heterotachy on the performance of different phylogenetic methods was examined using computer simulation for a four-species phylogeny. Maximum parsimony (MP) was reported to generally outperform maximum likelihood (ML). However, our comparisons of MP and ML methods using the methods and evaluation criteria employed in that study, but considering the possible range of proportions of sites involved in heterotachy, contradict their findings and indicate that, in fact, ML is significantly superior to MP even under heterotachy.

Classification↗

Inferring species phylogenies from multiple genes: concatenated sequence tree versus consensus gene tree.

Phylogenetic trees from multiple genes can be obtained in two fundamentally different ways. In one, gene sequences are concatenated into a super-gene alignment, which is then analyzed to generate the species tree. In the other, phylogenies are inferred separately from each gene, and a consensus of these gene phylogenies is used to represent the species tree. Here, we have compared these two approaches by means of computer simulation, using 448 parameter sets, including evolutionary rate, sequence length, base composition, and transition/transversion rate bias. In these simulations, we emphasized a worst-case scenario analysis in which 100 replicate datasets for each evolutionary parameter set (gene) were generated, and the replicate dataset that produced a tree topology showing the largest number of phylogenetic errors was selected to represent that parameter set. Both randomly selected and worst-case replicates were utilized to compare the consensus and concatenation approaches primarily using the neighbor-joining (NJ) method. We find that the concatenation approach yields more accurate trees, even when the sequences concatenated have evolved with very different substitution patterns and no attempts are made to accommodate these differences while inferring phylogenies. These results appear to hold true for parsimony and likelihood methods as well. The concatenation approach shows >95% accuracy with only 10 genes. However, this gain in accuracy is sometimes accompanied by reinforcement of certain systematic biases, resulting in spuriously high bootstrap support for incorrect partitions, whether we employ site, gene, or a combined bootstrap resampling approach. Therefore, it will be prudent to report the number of individual genes supporting an inferred clade in the concatenated sequence tree, in addition to the bootstrap support.

Animals↗

Behaviour problems in children and adolescents with seizure disorder: associations and risk factors.

PROBLEM: Fifty million people worldwide have epilepsy of whom 33 million are children. Children and adolescents with epilepsy are known to have high rates of behaviour problems and psychiatric co-morbidity. No studies on this topic have been conducted in developing countries, although 90% of such children live in the developing world. METHODS: The current study, set in Vellore in India, assessed the prevalence of psychopathology and its associations in children and adolescents with seizure disorder. One hundred and thirty two children were rated for psychopathology on the Child Behaviours Check List, and those who qualified as psychiatric cases were compared with those who did not. RESULTS: Seizure disorder was associated with significant psychopathology in 53.8% children. Belonging to a higher income group and living in an urban area (OR: 7.61, 95% CI: 2.78-20.8, p=0.0001), having longer than 3 years of illness (OR: 2.39, 95% CI: 2.18-5.67, p=0.03) and being treated by more than one anti-epileptic drug (OR: 3.08, 95% CI: 1.09-8.72, p=0.03) independently predicted psychopathology. CONCLUSIONS: Psychopathology reflected a complex interaction of seizures, socio-demographic factors and treatment related variables, in accord with studies in industrialised countries. Clinicians should be sensitive to identifying psychopathology since this may lead to effective interventions for this group of children.

Adolescent↗

Molecular clocks: four decades of evolution.

During the past four decades, the molecular-clock hypothesis has provided an invaluable tool for building evolutionary timescales, and has served as a null model for testing evolutionary and mutation rates in different species. Molecular clocks have also influenced the development of theories of molecular evolution. As DNA-sequencing technologies have progressed, the use of molecular clocks has increased, with a profound effect on our understanding of the temporal diversification of species and genomes.

Animals↗

Bilateral anterior shoulder dislocation: a case report.

Bilateral anterior shoulder dislocation is a very rare clinical entity. All the cases reported so far highlight a simultaneous bilateral shoulder dislocation. We report an unusual case, where the left shoulder dislocated first due to trauma followed by atraumatic dislocation of the right shoulder. A new manoeuvre--the Spaso Technique was used to reduce the dislocation.

Adult↗

Neglected traumatic hip dislocation in children.

Traumatic dislocation of the hip in children is a rare injury. We report the outcome of open reduction of neglected traumatic posterior hip dislocation in 18 children. All patients had posterior dislocation and no associated fracture. They presented to the hospital because of persisting pain, deformity, and limp that were present for a mean period of 16 weeks after injury (range, 6-52 weeks). Open reduction was done in all patients because none of the hips could be reduced by skeletal traction in abduction. All of the hips had varying degrees of avascular necrosis (osteonecrosis), with preservation of joint space as seen on radiographs. At short term followup, seventeen children had an excellent functional outcome. We suggest that open reduction is a satisfactory treatment for neglected hip dislocation in children because an anatomically placed femoral head maintains the stimulus for growth of the pelvis and the femur. It prevents deformity and maintains limb length.

Bone Wires↗

POSSUM scoring for laparoscopic cholecystectomy in the elderly.

BACKGROUND: Physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) scoring is a validated scoring system in the audit of surgical outcomes; however, evaluation of this system has mostly been applied to open surgical techniques. The present study examines the validity of POSSUM in predicting morbidity and mortality in patients undergoing laparoscopic cholecystectomy (LC) with the recognized risk factor for postoperative mortality of advanced age. METHODS: All patients aged 80 years or over undergoing LC in one surgical unit between January 1993 and December 1999 were identified from the surgical operations database of the hospital. Case-note review was used to collate data in terms of clinical and operative factors as described in POSSUM. Observed/POSSUM estimated (O/E) ratio of morbidity and 30-day mortality were calculated. RESULTS: Laparoscopic cholecystectomy was performed in 76 patients aged 80 years or over during the study period. Of these patients, case notes for 70 patients (92%) were available for review. Median (range) age was 83 years (80-93 years) and median (range) American Society of Anesthesiologists score was 2 (2-4). Twenty-six (34%) of 70 patients underwent cholecystectomy during an acute admission. The mean physiology severity score was 23 and operative severity score, 8. A significant postoperative morbidity was observed in 15 (22%) of 70 patients. There was no 30-day mortality. Using exponential analysis, POSSUM predicted morbidity in 15 patients and mortality in seven patients. Thus, O/E ratios for morbidity and mortality were 1 and 0, respectively. CONCLUSION: POSSUM scoring performs well in predicting morbidity, but overpredicts mortality, after LC in patients aged over 80 years. An assessment of its application to other laparoscopic procedures merits evaluation.

Age Factors↗

Clinical and laboratory features and response to treatment in patients presenting with vitamin B12 deficiency-related neurological syndromes.

AIMS AND OBJECTIVES: To study the clinical and laboratory features of patients admitted with vitamin B12 deficiency-related (B12def) neurological syndromes. SETTINGS AND DESIGN: A hospital-based retrospective and prospective study conducted at a referral teaching hospital. MATERIALS AND METHODS: Consecutive patients admitted with vitamin B12 deficiency-related neurological disorders during a three-year period from June 2000 to May 2003 were included. Data regarding clinical and laboratory features were obtained. Follow-up was done at least six months following treatment with parenteral vitamin B12. Chi-square test was used for statistical analysis. RESULTS: A total of 63 patients (52 males) with a mean age of 46.2 years were studied. The mean duration of symptoms at presentation was 10.3 months. Myeloneuropathy (54%) was the commonest neurological manifestation, followed by myeloneuropathy with cognitive dysfunction (34%), and peripheral neuropathy (9%). Neuropsychiatric manifestations and dementia were observed in 38% and 19% of patients respectively. All the patients had megaloblastic changes in the bone marrow smear. Eleven (17.5%) patients had both hemoglobin and the mean corpuscular volume (MCV) within the normal range. Follow-up after at least six months of therapy with parenteral B12 showed improvement in 54% patients. CONCLUSIONS: A high index of suspicion of B12def is required in patients presenting with myelopathy, cognitive decline, or neuropathy. A normal hemoglobin or MCV does not exclude B12def; therefore, other tests such as bone marrow smear and serum vitamin B12 assay are essential, as the condition is often reversible with treatment.

Adult↗

Positron emission tomography in neurological diseases.

Positron emission tomography (PET) is the study of human physiology by electronic detection of positron-emitting radiopharmaceuticals. It is one of the noninvasive technologies that can measure the metabolic and functional activity of living tissue. Positron emission tomography finds its clinical applications in broadly three specialties--oncology, cardiology, and neurology. The current review focuses on its indications in neurological diseases. Recently published literature on the use of PET in neurology has been thoroughly analyzed. Several reports regarding the usage of PET in epilepsy, stroke, dementia, and movement disorders are available. Positron emission tomography does not appear to be useful as a primary or sole imaging technique in these conditions. On the other hand, it is useful in very specific situations, which have been elaborated in the review. It is also noteworthy that PET is complementary to the computed tomography/magnetic resonance imaging findings and data obtained from combining these modalities can be valuable in situations such as localization of the epileptogenic focus in cases of refractory epilepsy or for prediction of the outcome after thrombolysis in acute ischemic stroke. The major handicaps in widespread use of PET appear to be its lack of availability and its relatively high cost. Nevertheless, a review such as this would be helpful in judiciously selecting those patients who would benefit from undergoing a PET scan, at a time when PET imaging facility is likely to be available soon in the Indian private sector.

Brain Neoplasms↗