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1.  Optimization of tractography of the optic radiations 
Human brain mapping  2012;35(2):683-697.
Imaging and delineation of the optic radiations (OpR) remains challenging, despite repeated attempts to achieve reliable validated tractography of this complex structure. Previous studies have used varying methods to generate representations of the OpR which differ markedly from one another and, frequently, from the OpR’s known structure. We systematically examined the influence of a key variable that has differed across previous studies, the tractography seed region, in 13 adult participants (9 male; mean age 31 years; sd. 8.7 years; range 16–47). First we compared six seed regions at the lateral geniculate nucleus (LGN) and sagittal stratum based on the literature and known OpR anatomy. Three of the LGN regions seeded streamlines consistent with the OpR’s three ‘bundles’ while a fourth seeded streamlines consistent with each of the three bundles. The remaining two generated OpR streamlines unreliably and inconsistently. Two stratum regions seeded the radiations. This analysis identified a set of optimal ROI for seeding OpR tractography and important inclusion and exclusion ROI. An optimized approach was then used to seed LGN regions to the stratum. The radiations, including streamlines consistent with Meyer’s Loop, were streamlined in all cases. Streamlines extended 0.2±2.4mm anterior to the tip of the anterior horn of the lateral ventricle. These data suggest some existing approaches likely seed representations of the OpR that are visually plausible but do not capture all OpR components, and that using an optimized combination of regions seeded previously allows optimal mapping of this complex structure.
doi:10.1002/hbm.22204
PMCID: PMC4083652  PMID: 23225566
Diffusion-weighted MRI; DWI; tractography; optic radiations; Meyer’s Loop
2.  Impaired Language Pathways in Tuberous Sclerosis Complex Patients with Autism Spectrum Disorders 
Cerebral Cortex (New York, NY)  2012;23(7):1526-1532.
The purpose of this study was to examine the relationship between language pathways and autism spectrum disorders (ASDs) in patients with tuberous sclerosis complex (TSC). An advanced diffusion-weighted magnetic resonance imaging (MRI) was performed on 42 patients with TSC and 42 age-matched controls. Using a validated automatic method, white matter language pathways were identified and microstructural characteristics were extracted, including fractional anisotropy (FA) and mean diffusivity (MD). Among 42 patients with TSC, 12 had ASD (29%). After controlling for age, TSC patients without ASD had a lower FA than controls in the arcuate fasciculus (AF); TSC patients with ASD had even a smaller FA, lower than the FA for those without ASD. Similarly, TSC patients without ASD had a greater MD than controls in the AF; TSC patients with ASD had even a higher MD, greater than the MD in those without ASD. It remains unclear why some patients with TSC develop ASD, while others have better language and socio-behavioral outcomes. Our results suggest that language pathway microstructure may serve as a marker of the risk of ASD in TSC patients. Impaired microstructure in language pathways of TSC patients may indicate the development of ASD, although prospective studies of language pathway development and ASD diagnosis in TSC remain essential.
doi:10.1093/cercor/bhs135
PMCID: PMC3673171  PMID: 22661408
arcuate fasciculus; diffusion tensor imaging; neuroanatomy; tractography; white matter
3.  Diffusion tensor imaging and related techniques in tuberous sclerosis complex: review and future directions 
Future neurology  2013;8(5):583-597.
In this article, the authors aim to introduce the nonradiologist to diffusion tensor imaging (DTI) and its applications to both clinical and research aspects of tuberous sclerosis complex. Tuberous sclerosis complex is a genetic neurocutaneous syndrome with variable and unpredictable neurological comorbidity that includes refractory epilepsy, intellectual disability, behavioral abnormalities and autism spectrum disorder. DTI is a method for modeling water diffusion in tissue and can noninvasively characterize microstructural properties of the brain. In tuberous sclerosis complex, DTI measures reflect well-known pathological changes. Clinically, DTI can assist with detecting the epileptogenic tuber. For research, DTI has a putative role in identifying potential disease biomarkers, as DTI abnormalities of the white matter are associated with neurocognitive morbidity including autism. If indeed DTI changes parallel phenotypical changes related to the investigational treatment of epilepsy, cognition and behavior with mTOR inhibitors, it will facilitate future clinical trials.
doi:10.2217/fnl.13.37
PMCID: PMC3904372  PMID: 24489482
autism spectrum disorders; behavior; cognition; diffusion tensor imaging; epilepsy; MRI; mTOR serine–threonine kinases; tuberous sclerosis complex
4.  Characterizing the DIstribution of Anisotropic MicrO-structural eNvironments with Diffusion-weighted imaging (DIAMOND) 
Diffusion-weighted imaging (DWI) enables investigation of the brain microstructure by probing natural barriers to diffusion in tissues. In this work, we propose a novel generative model of the DW signal based on considerations of the tissue microstructure that gives rise to the diffusion attenuation. We consider that the DW signal can be described as the sum of a large number of individual homogeneous spin packets, each of them undergoing local 3-D Gaussian diffusion represented by a diffusion tensor. We consider that each voxel contains a number of large scale microstructural environments and describe each of them via a matrix-variate Gamma distribution of spin packets. Our novel model of DIstribution of Anisotropic MicrOstructural eNvironments in DWI (DIAMOND) is derived from first principles. It enables characterization of the extra-cellular space, of each individual white matter fascicle in each voxel and provides a novel measure of the microstructure heterogeneity. We determine the number of fascicles at each voxel with a novel model selection framework based upon the minimization of the generalization error. We evaluate our approach with numerous in-vivo experiments, with cross-testing and with pathological DW-MRI. We show that DIAMOND may provide novel biomarkers that captures the tissue integrity.
PMCID: PMC4029840  PMID: 24505801
5.  FOXC1 regulates the functions of human basal-like breast cancer cells by activating NF-κB signaling 
Oncogene  2012;31(45):4798-4802.
Human basal-like breast cancer (BLBC) is an enigmatic and aggressive malignancy with a poor prognosis. There is an urgent need to identify therapeutic targets for BLBC because current treatment modalities are limited and not effective. The forkhead box transcription factor FOXC1 has recently been identified as a critical functional biomarker for BLBC. However, how it orchestrates BLBC cells was not clear. Here we show that FOXC1 activates the transcription factor NF-κB in BLBC cells by increasing p65/RelA protein stability. High NF-κB activity has been associated with estrogen receptor-negative breast cancer, particularly BLBC. The effect of FOXC1 on p65/RelA protein stability is mediated by increased expression of Pin1, a peptidyl-prolyl isomerase. FOXC1 requires NF-κB for its regulation of cell proliferation, migration, and invasion. Notably, FOXC1 overexpression renders breast cancer cells more susceptible to pharmacologic inhibition of NF-κB. These results suggest that BLBC cells may rely on FOXC1-driven NF-κB signaling. Interventions of this pathway may provide modalities for the treatment of BLBC.
doi:10.1038/onc.2011.635
PMCID: PMC3961006  PMID: 22249250
basal-like breast cancer; FOXC1; NF-κB; p65/RelA; Pin1; protein stability
6.  Electrode Localization for Planning Surgical Resection of the Epileptogenic Zone in Pediatric Epilepsy 
Purpose
In planning for a potentially curative resection of the epileptogenic zone in patients with pediatric epilepsy, invasive monitoring with intracranial EEG is often used to localize the seizure onset zone and eloquent cortex. A precise understanding of the location of subdural strip and grid electrodes on the brain surface, and of depth electrodes in the brain in relationship to eloquent areas is expected to facilitate pre-surgical planning.
Methods
We developed a novel algorithm for the alignment of intracranial electrodes, extracted from post-operative CT, with pre-operative MRI. Our goal was to develop a method of achieving highly accurate localization of subdural and depth electrodes, in order to facilitate surgical planning. Specifically, we created a patient-specific 3D geometric model of the cortical surface from automatic segmentation of a pre-operative MRI, automatically segmented electrodes from post-operative CT, and projected each set of electrodes onto the brain surface after alignment of the CT to the MRI. Also, we produced critical visualization of anatomical landmarks, e.g. vasculature, gyri, sulci, lesions or eloquent cortical areas, which enables the epilepsy surgery team to accurately estimate the distance between the electrodes and the anatomical landmarks, which might help for better assessment of risks and benefits of surgical resection.
Results
Electrode localization accuracy was measured using knowledge of the position of placement from 2D intra-operative photographs in ten consecutive subjects who underwent intracranial EEG for pediatric epilepsy. Average spatial accuracy of localization was 1.31±0.69mm for all 385 visible electrodes in the photos.
Conclusions
In comparison to previously reported approaches, our algorithm is able to achieve more accurate alignment of strip and grid electrodes with minimal user input. Unlike manual alignment procedures, our algorithm achieves excellent alignment without time consuming and difficult judgements from an operator.
doi:10.1007/s11548-013-0915-6
PMCID: PMC3955988  PMID: 23793723
Pediatric Epilepsy; Intracranial EEG; Electrode Localization; Epilepsy Surgery Planning
7.  Refractory status epilepticus 
Annals of Indian Academy of Neurology  2014;17(Suppl 1):S32-S36.
Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED), i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs) and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits.
doi:10.4103/0972-2327.128647
PMCID: PMC4001215  PMID: 24791086
Midazolam; pentobarb; propofol; refractory status epilepticus; status epilepticus
8.  Magnetoencephalography: Basic principles 
Annals of Indian Academy of Neurology  2014;17(Suppl 1):S107-S112.
Magnetoencephalography (MEG) is the measurement of the magnetic field generated by the electrical activity of neurons. It is usually combined with a magnetic resonance imaging to get what is called magnetic source imaging. The technology that has helped record these minute magnetic fields is super-conducting quantum interference detector which is like a highly sensitive magnetic field meter. To attenuate the external magnetic noise the MEG is housed inside a magnetically shielded room. The actual sensors recording magnetic fields are magnetometers and/or gradiometers. MEG fields pass through the head without any distortion. This is a significant advantage of MEG over electroencephalography. MEG provides a high spatial and temporal resolution. The recording and identification information should be according to the American Clinical Magnetoencephalography Society guidelines published in 2011. MEG currently has two approved indications in the United States, one is for pre-operative brain mapping and the other is for use in epilepsy surgery. MEG studies have shown functional brain tissue inside brain tumors.
doi:10.4103/0972-2327.128676
PMCID: PMC4001219  PMID: 24791076
Cortical mapping; epilepsy; magnetic source imaging; magnetoencephalography
9.  An MRI Study of Cerebellar Volume in Tuberous Sclerosis Complex 
Pediatric neurology  2013;48(2):105-110.
The cerebellum plays an important role in motor learning and cognition, and structural cerebellar abnormalities have been associated with cognitive impairment. In tuberous sclerosis complex, neurological outcome is highly variable, and no consistent imaging or pathological determinant of cognition has been firmly established. The cerebellum calls for specific attention as mouse models of tuberous sclerosis complex have demonstrated a loss of cerebellar Purkinje cells and cases of human histological data have demonstrated a similar loss in patients. We hypothesized that there might be a common cerebellar finding in tuberous sclerosis complex that could be measured as morphometric changes with magnetic resonance imaging. Using a robust, automated image analysis procedure, we studied 36 patients with tuberous sclerosis complex and age-matched controls and observed significant volume loss among patients in the cerebellar cortices and vermis. Furthermore, this effect was strongest in a subgroup of 19 patients with a known, pathogenic mutation of the tuberous sclerosis 2 gene and impacted all cerebellar structures. We conclude that patients with tuberous sclerosis complex exhibit volume loss in the cerebellum, and this loss is larger and more widespread in patients with a tuberous sclerosis 2 mutation.
doi:10.1016/j.pediatrneurol.2012.10.011
PMCID: PMC3763730  PMID: 23337002
10.  Papillary Carcinoma of the Breast- Case Reports and Review of Literature Regarding Management Guidelines 
The Indian Journal of Surgery  2012;74(6):510-512.
Papillary carcinoma of the breast is a very rare entity accounting for approx 1 % of all breast carcinomas. The diagnosis is difficult due to different clinical and radiological features. Pathological diagnosis is conclusive. Being aware of the diagnostic difficulties and differences in management from the more commonly reported IDC, makes it easier to treat these patients. Because this is an uncommon disease, we report here 2 cases recently diagnosed and treated in our hospital. We have also reviewed the literature regarding the diagnosis, treatment and prognosis of these patients.
doi:10.1007/s12262-012-0524-6
PMCID: PMC3537999  PMID: 24293915
Papillary; Carcinoma; Breast
11.  Effect of Vitamin E Supplementation on Biochemical Parameters in Pesticides Sprayers of Grape Gardens of Western Maharashtra (India) 
The aim of this study was to see the biochemical effects of pesticides on sprayers of grape gardens before and after 15 days of vitamin E supplementations in Western Maharashtra (India), who were occupationally exposed to various pesticides over a long period of time (about 5 to 15 years). Blood samples were collected from all study group subjects for biochemical parameters assays before and after 15 days of vitamin E supplementation. Sprayers of grape gardens were given 400 mg of vitamin E tablet/day for 15 days. After 15 days of vitamin E supplementation to sprayers of grape gardens, we observed significantly decreased aspartate transaminase (10.88 %, P < 0.05, r = 0.88), alanine transaminase (25.92 %, P < 0.01, r = 0.46) and total proteins (3.32 %, P < 0.01, r = 0.33), whereas, no statistically significant change was found in serum acetyl cholinesterase, C-reactive proteins, albumin (ALB), globulins and ALB/globulin ratio as compared to before vitamin E supplementation. Sprayers of grape gardens, who received vitamin E supplementation, showed significantly decreased serum lipid peroxide (LP) (18.75 %, P < 0.001, r = 0.63) and significantly increased RBC-superoxide dismutase (SOD) (12.88 %, P < 0.001, r = 0.85), RBC-Catalase (CAT) (24.49 %, P < 0.001, r = 0.70), plasma ceruloplasmin (CP) (4.6 %, P < 0.01, r = 0.80), serum zinc (4.57 %, P < 0.01, r = 0.83) and serum copper (4.37 %, P < 0.01, r = 0.79) as compared to values before vitamin E supplementation. These results showed that vitamin E supplementation has ameliorating effects on these transaminase enzymes, suggesting that it may have a protective effect on liver, from pesticides induced damage. In this study vitamin E supplementation might have decreased LP levels by breaking chain reaction of lipid peroxidation. Present results indicate that vitamin E plays a crucial role in restoring the antioxidant enzymes such as SOD, CAT and CP, in population exposed to pesticides. This helps to enhance its antioxidant ability. Therefore, it is suggested that farmers, pesticide applicators, workers in the pesticide industry and other pesticide users, who come in regular contact with pesticides, may be benefited by supplementation with vitamin E.
doi:10.1007/s12291-012-0207-x
PMCID: PMC3358367  PMID: 23543683
Acetylcholinesterase; C-reactive proteins; Aspartate transaminase; Alanine transaminase; Lipid peroxidation; Superoxide dismutase; Catalase; Ceruloplasmin; Glutathione-S-transferase
12.  DTI Assessment of the Brainstem White Matter Tracts in Pediatric BSG Before and After Therapy: A Report from the Pediatric Brain Tumor Consortium 
Purpose
To assess changes in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values in brainstem gliomas in children and to observe the temporal evolution of changes in the white matter tracts following therapy using diffusion tensor imaging (DTI) analysis.
Methods
Serial ADC and FA measurements were obtained in 3 patients with newly diagnosed brainstem gliomas on two approved treatment protocols. Values were compared with a set of normative ADC, FA, and eigenvalues of age-matched children of the corticospinal, transverse pontine and medial lemniscal tracts. Fiber tracking of the tracts coursing through the brainstem was performed using standard diffusion tractography analysis.
Results
We found increased ADC values within tumor at baseline compared to age-matched controls, with subsequent drop following treatment and subsequent increase with recurrence. Correspondingly, FA values were reduced at presentation, but transiently recovered during the phase of tumor response to treatment, and finally decreased significantly during tumor progression. These changes were concordant with the tractography analysis of white matter tracts in the brainstem. Based on these results, we suggest that initial changes in ADC and FA values reflects tract infiltration by tumor, but not complete disruption, whereas tumor progression results in complete loss of anisotropy possibly due to tract disruption.
Conclusion
Serial changes in ADC and FA values and tractography data in pediatric brainstem gliomas suggest initial tumor infiltration, with transient improvement on treatment and subsequent loss of tract anisotropy during tumor progression. This technique may have potential use in assessing response to treatment regimens for pediatric brainstem gliomas.
doi:10.1007/s00381-010-1323-7
PMCID: PMC3598014  PMID: 21052693
MRI; diffusion tensor imaging; brainstem glioma; pediatrics
14.  Loss of white matter microstructural integrity is associated with adverse neurological outcome in Tuberous Sclerosis Complex 
Academic Radiology  2012;19(1):17-25.
Rationale and Objectives
Tuberous Sclerosis Complex (TSC) is a genetic neurocutaneous syndrome in which cognitive and social-behavioral outcomes for patients vary widely in an unpredictable manner. The cause of adverse neurological outcome remains unclear. We investigated the hypothesis that disordered white matter and abnormal neural connectivity are associated with adverse neurological outcome.
Materials and Methods
Structural and diffusion magnetic resonance imaging was carried out in 40 subjects with TSC (age range 0.5 – 25 years, mean age 7.2 and median age 5 years), 12 of whom had autism spectrum disorders (ASD), and in 29 age-matched controls. Tractography of the corpus callosum was used to define a 3-dimensional volume of interest. Regional averages of four diffusion scalar parameters of the callosal projections were calculated for each subject. These were the average fractional anisotropy (AFA) and average mean, radial and axial diffusivity (AMD, ARD, AAD).
Results
Subjects with TSC had significantly lower AFA and higher AMD, ARD and AAD values compared to controls. Subjects with TSC and ASD had significantly lower AFA values compared to those without ASD, and compared to controls. TSC subjects without ASD had similar AFA values compared to controls.
Conclusion
Diffusion tensor scalar parameters provided measures of properties of the three-dimensional callosal projections. In TSC, changes in these parameters may reflect microstructural changes in myelination, axonal integrity, or extracellular environment. Alterations in white matter microstructural properties were associated with TSC and larger changes were associated with TSC and ASD, thus establishing a relationship between altered white matter microstructural integrity and brain function.
doi:10.1016/j.acra.2011.08.016
PMCID: PMC3343770  PMID: 22142677
15.  Should Sputum Smear Examination Be Carried Out at the End of the Intensive Phase and End of Treatment in Sputum Smear Negative Pulmonary TB Patients? 
PLoS ONE  2012;7(11):e49238.
Background
The Indian guidelines on following up sputum smear-negative Pulmonary tuberculosis (PTB) patients differ from the current World Health Organization (WHO) guidelines in that the former recommends two follow up sputum examinations (once at the end of intensive phase and the other at the end of treatment) while the latter recommends only one follow up sputum smear microscopy examination, which is done at the end of the intensive phase. This study was conducted to examine if there was any added value in performing an additional sputum smear examination at the end of treatment within the context of a national TB program.
Methods
This study was a descriptive record based review conducted in nine tuberculosis (TB) units in Delhi, India. All consecutive new sputum smear-negative PTB patients registered in these nine TB units from 1st January 2009 to 31st December 2009 were included in the study.
Results
Of 2567 new sputum smear-negative TB patients, 1973 (90%) had sputum specimens examined at the end of the intensive phase, of whom 36 (2%) were smear-positive: the majority (n = 28) successfully completed treatment with either the same or a re-treatment regimen. At treatment completion, 1766 (85%) patients had sputum specimens examined, of whom 16 (0.9%) were smear-positive: all these were changed to a re-treatment regimen. Amongst the sputum-positive patients identified as a result of follow up (n = 52), four were diagnosed with multi-drug resistant TB (MDR-TB), three of whom were detected after smear examination at the end of treatment.
Conclusions
Given the high burden of TB in India, a 0.9% additional yield of smear-positive sputum smears at the end of treatment translates to 3,297 cases of smear-positive PTB. End-of-treatment smear is a low-yield strategy for detection of smear-positive TB cases, although further studies are needed to determine its population-level impact and cost, particularly in relation to other TB control interventions.
doi:10.1371/journal.pone.0049238
PMCID: PMC3494682  PMID: 23152880
16.  Factors influencing consumer adoption of USB-based Personal Health Records in Taiwan 
Background
Usually patients receive healthcare services from multiple hospitals, and consequently their healthcare data are dispersed over many facilities’ paper and electronic-based record systems. Therefore, many countries have encouraged the research on data interoperability, access, and patient authorization. This study is an important part of a national project to build an information exchange environment for cross-hospital digital medical records carried out by the Department of Health (DOH) of Taiwan in May 2008. The key objective of the core project is to set up a portable data exchange environment in order to enable people to maintain and own their essential health information.
This study is aimed at exploring the factors influencing behavior and adoption of USB-based Personal Health Records (PHR) in Taiwan.
Methods
Quota sampling was used, and structured questionnaires were distributed to the outpatient department at ten medical centers which participated in the DOH project to establish the information exchange environment across hospitals. A total of 3000 questionnaires were distributed and 1549 responses were collected, out of those 1465 were valid, accumulating the response rate to 48.83%.
Results
1025 out of 1465 respondents had expressed their willingness to apply for the USB-PHR. Detailed analysis of the data reflected that there was a remarkable difference in the “usage intention” between the PHR adopters and non-adopters (χ2 =182.4, p < 0.001). From the result of multivariate logistic regression analyses, we found the key factors affecting patients’ adoption pattern were Usage Intention (OR, 9.43, 95%C.I., 5.87-15.16), Perceived Usefulness (OR, 1.60; 95%C.I., 1.11-2.29) and Subjective Norm (OR, 1.47; 95%C.I., 1.21-1.78).
Conclusions
Higher Usage Intentions, Perceived Usefulness and Subjective Norm of patients were found to be the key factors influencing PHR adoption. Thus, we suggest that government and hospitals should promote the potential usefulness of PHR, and physicians should encourage patients' to adopt the PHR.
doi:10.1186/1472-6963-12-277
PMCID: PMC3465237  PMID: 22925029
Personal Health Records (PHR); Technology Acceptance Model (TAM); Adoption, Behavior, Taiwan
17.  The biomechanics of fast prey capture in aquatic bladderworts 
Biology Letters  2011;7(4):547-550.
Carnivorous plants match their animal prey for speed of movements and hence offer fascinating insights into the evolution of fast movements in plants. Here, we describe the mechanics of prey capture in aquatic bladderworts Utricularia stellaris, which prey on swimming insect larvae or nematodes to supplement their nitrogen intake. The closed Utricularia bladder develops lower-than-ambient internal pressures by pumping out water from the bladder and thus setting up an elastic instability in bladder walls. When the external sensory trigger hairs on their trapdoor are mechanically stimulated by moving prey, the trapdoor opens within 300–700 μs, causing strong inward flows that trap their prey. The opening time of the bladder trapdoor is faster than any recorded motion in carnivorous plants. Thus, Utricularia have evolved a unique biomechanical system to gain an advantage over their animal prey.
doi:10.1098/rsbl.2011.0057
PMCID: PMC3130236  PMID: 21389013
carnivorous plants; Utricularia; high-speed videography
18.  Does metastasectomy improve survival in patients with Stage IV melanoma? A cancer registry analysis of outcomes 
Journal of surgical oncology  2011;104(2):111-115.
Introduction
Patients with Stage IV melanoma have limited therapeutic options with few long term survivors. Our goal was to study the impact of metastasectomy on survival in these patients.
Methods
Patients with Stage IV melanoma were identified from the Surveillance, Epidemiology and End Results (SEER) database (1988–2006). Those who had metastasectomy performed were compared with patients that did not.
Results
The median age of the study population (n= 4229) was 63 years and median survival was 7 months. Patients who underwent metastasectomy (33.6%) had an improved median and 5-year overall survival as compared to patients who did not; 12 months vs. 5 months and 16% vs. 7%, p <0.001). In patients with M1a disease (n= 1994), this improvement of survival following metastasectomy was enhanced; median survival of 14 months vs. 6 months and 5-year overall survival of 20% vs. 9% (p <0.001). Younger age and diagnosis from 2001–2006 were predictors of metastasectomy. Metastasectomy was an independent and significant predictor of survival for the entire cohort (HR 0.59, 95% CI 0.55– 0.63).
Conclusions
Metastasectomy in patients with Stage IV melanoma may improve long term survival. The true therapeutic benefit, if any, of metastatectomy needs to be determined by a randomized trial.
doi:10.1002/jso.21903
PMCID: PMC3199373  PMID: 21381040
Stage IV melanoma; metastasectomy; survival
19.  Diphtheria, Tetanus, and Pertussis Immunity in Indian Adults and Immunogenicity of Td Vaccine 
ISRN Microbiology  2011;2011:745868.
Rise of diphtheria cases in adults is a cause of concern worldwide. Pertussis is also now affecting adults. We assessed serum levels of tetanus, diphtheria and pertussis antibodies in 62 adults in Pune, India, who had missed their primary immunization. All adults were then given three doses of tetanus-diphtheria (Td) vaccine at 0, 1, and 6 months. All adults were immune to tetanus but 78% had long-term protection. For diphtheria, 88% were protected but only 9% had long term immunity. Only 60% were immune to pertussis. After three doses of the vaccine, long term immunity to both tetanus and diphtheria increased to 87% and 97%, respectively (P < 0.05). Geometric mean titres (GMT) of both antibodies also increased significantly. The vaccine caused minor local reactions and mild fever in a few subjects. There is need of three doses of Td vaccination in those Indian adults, who missed their primary immunization. Susceptibility to pertussis also needs to be further explored.
doi:10.5402/2011/745868
PMCID: PMC3658482  PMID: 23724309
20.  Mayo Clinic Consensus Recommendations for the Depth of Excision in Primary Cutaneous Melanoma 
Mayo Clinic Proceedings  2011;86(6):522-528.
Currently, no data from randomized controlled clinical trials are available to guide the depth of resection for intermediate-thickness primary cutaneous melanoma. Thus, we hypothesized that substantial variability exists in this aspect of surgical care. We have summarized the literature regarding depth of resection and report the results of our survey of surgeons who treat melanoma. Most of the 320 respondents resected down to, but did not include, the muscular fascia (extremity, 71%; trunk, 66%; and head and neck, 62%). However, significant variation exists. We identified variability in our own practice and have elected to standardize this common aspect of routine surgical care across our institution. In light of the lack of evidence to support resection of the deep muscular fascia, we have elected to preserve the muscular fascia as a matter of routine, except when a deep primary melanoma or thin subcutaneous tissue dictates otherwise.
doi:10.4065/mcp.2011.0059
PMCID: PMC3104911  PMID: 21628616
21.  Extra-anatomical bypass grafting – a single surgeon's experience 
INTRODUCTION
Extra-anatomical bypass grafting is a recognised method of lower limb re-vascularisation in high-risk patients who cannot tolerate aortic cross clamping, or in those with a hostile abdomen. We present a single surgeon series of such procedures and determine relevant outcomes.
PATIENTS AND METHODS
A retrospective review was performed on a prospectively maintained database of patients undergoing femoro-femoral or axillo-femoral bypass surgery between 1986 and 2004.
RESULTS
Patency rates for femoral (n = 28; 32%) versus axillary (n = 59; 68%) bypass procedures at 1 month, 1, 3 and 5 years were (92% vs 93%), (69% vs 85%), (60% vs 72%) and (55% vs 67%), respectively. Patient survival rates for the corresponding procedures and time intervals were (96% vs 90%), (96% vs 67%), (85% vs 45%) and (73% vs 38%) and revealed a significantly lower survival rate in those undergoing axillary procedures (P = 0.002). Limb salvage rates were calculated at (100% vs 91%), (96% vs 84%), (96% vs 81%) and (92% vs 81%) with no statistically significant difference found between the two groups (P = 0.124). Two-thirds of the patients who required major amputation died within 12 months of surgery.
CONCLUSIONS
Acceptable 30-day morbidity, long-term primary patency and survival rates are obtainable in patients suitable for extra-anatomical bypass surgery despite having significant co-morbidities. We have shown 5-year patency rates in those that survive axillary procedures to be as good as those undergoing femoral procedures. Furthermore, surviving patients who evade amputation within a year have an excellent chance of long-term limb salvage.
doi:10.1308/003588410X12664192076890
PMCID: PMC3182793  PMID: 20522294
Extra-anatomical bypass grafting; Femoro-femoral; Axillo-femoral; Limb salvage
22.  Antennal regulation of migratory flight in the neotropical moth Urania fulgens 
Biology Letters  2010;6(3):406-409.
Migrating insects use their sensory systems to acquire local and global cues about their surroundings. Previous research on tethered insects suggests that, in addition to vision and cephalic bristles, insects use antennal mechanosensory feedback to maintain their airspeeds. Owing to the large displacements of migratory insects and difficulties inherent in tracking single individuals, the roles of these sensory inputs have never been tested in freely migrating insects. We tracked individual uraniid moths (Urania fulgens) as they migrated diurnally over the Panama Canal, and measured airspeeds and orientation for individuals with either intact or amputated flagella. Consistent with prior observations that antennal input is necessary for flight control, 59 per cent of the experimental moths could not fly after flagella amputation. The remaining fraction (41%) was flight-capable and maintained its prior airspeeds despite severe reduction in antennal input. Thus, maintenance of airspeeds may not involve antennal input alone, and is probably mediated by other modalities. Moths with amputated flagella could not recover their proper migratory orientations, suggesting that antennal integrity is necessary for long-distance navigation.
doi:10.1098/rsbl.2009.1073
PMCID: PMC2880068  PMID: 20181558
insect migration; antenna; flight
23.  Sentinel Node Biopsy in Melanoma 
Journal of surgical oncology  2010;101(8):669-676.
Since its first description in 1990, sentinel node (SN) biopsy has become the standard for accurate staging of a melanoma-draining regional lymphatic basin. This minimally invasive, multidisciplinary technique can detect occult metastases by selective sampling and focused pathologic analysis of the first nodes on the afferent lymphatic pathway from a primary cutaneous melanoma. An understanding of preoperative lymphoscintigraphy, intraoperative lymphatic mapping, and the definition of SN are critical for surgical expertise with SN biopsy.
doi:10.1002/jso.21581
PMCID: PMC2879706  PMID: 20512942
Sentinel node biopsy; lymphoscintigraphy
24.  Optimal surgical technique, use of intra-operative cholangiography (IOC), and management of acute gallbladder disease: the results of a nation-wide survey in the UK and Ireland 
INTRODUCTION
There is debate on optimal techniques that reduce bile duct injury during laparoscopic cholecystectomy (LC). A national survey of Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS) members was carried out to determine current surgical practice for gallstones, including the use of intra-operative cholangiography (IOC) or critical view of safety to reduce the risk of bile duct injury.
SUBJECTS AND METHODS
An anonymous postal survey was sent to all 417 AUGIS members. Data on grade of surgeon, place of work (district general hospital, teaching), subspecialty, number LC per year, use of IOC, critical view of safety, and management of stones detected during surgery were collated.
RESULTS
There was a 36% (152/417) response – 134 (88%) from consultant surgeons (36, HPB; 106,OG; 64, DGH; 88, teaching hospital). Of these, 38% performed > 100 LC per year, 36% 50–100 LC per year, and 22% 25–50 LC per year. IOC was routine for 24%; and selective for 72%. Critical view of Calot's triangle was advocated by 82%. Overall, 55% first clip and divide the cystic artery, whereas 41% first clip and divide the cystic duct. Some 39% recommend IOC and 23% pre-oper-ative MRCP if dilated common bile duct (CBD) is noted on pre-operative ultrasound. When bile duct stones are identified on IOC, 61% perform laparoscopic CBD exploration (LCBDE), 25% advise postoperative ERCP, and 13% perform either LCBDE or ERCP. Overall, 88% (n = 134) recommend index cholecystectomy for acute pathology, and this is more likely in a teaching hospital setting (P= 0.003). Laparoscopic CBD exploration was more likely to be performed in university hospitals (P< 0.05).
CONCLUSIONS
A wide dissection of Calot's triangle to provide a critical view of safety is the technique most commonly recommended by AUGIS surgeons (83%) to minimise risk of bile duct injury, in contrast to 24% that recommend routine IOC. The majority (88%) of AUGIS surgeons advise index admission cholecystectomy for acute gallbladder disease.
doi:10.1308/003588410X12628812458617
PMCID: PMC3025204  PMID: 20501016
Gallbladder disease; Intra-operative cholangiography; Calot's triangle; UK audit
25.  An unusual branching pattern of common and external carotid artery in a human cadaver: a case report 
The Australasian Medical Journal  2011;4(4):180-182.
During a routine dissection in the Department of Anatomy of the Rural Medical College, Loni, we found a rare variation in branching pattern of the common carotid artery (CCA) and external carotid artery (ECA) bilaterally. The knowledge of possible anatomical variations of CCA and ECA are especially important in the surgeries of head, neck and face; and also for the radiologist to understand and interpret carotid system imaging when undertaking cerebral angiography. This case and the clinical significance of this variation are reported in this paper.
doi:10.4066/AMJ.2011.637
PMCID: PMC3562896  PMID: 23393509
Common carotid artery; external carotid artery; superior thyroid artery,; linguo-facial trunk; ascending pharyngeal artery; occipital artery

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