Diagnostic imaging of salivary glands has been revolutionized with the advent of cross-sectional imaging modalities like CT and MR imaging. In the era before CT, imaging of the salivary glands was relatively unrewarding and was used uncommonly by ear-nose-throat surgeons. Early diagnostic tests like plain films and sialography evaluated dilated parotid ducts and calculus disease within ducts or glands. Full evaluation of salivary glands, especially deep lobes of parotid gland and masses of minor salivary glands, was not possible by these methods, however. Imaging of the parotid glands has developed significantly since that time. CT and MR imaging greatly compliment physical and endoscopic examinations (and previous favorites like sialography) by direct visualization of previously blind areas of the salivary glands and extension of the disease process in surrounding tissue planes.

Freezing of gait (FOG) is arguably the most severe symptom associated with Parkinson's disease (PD), and often occurs while performing dual tasks or approaching narrowed and cluttered spaces. While it is well known that visual cues alleviate FOG, it is not clear if this effect may be the result of cognitive or sensorimotor mechanisms. Nevertheless, the role of vision may be a critical link that might allow us to disentangle this question. Gaze behaviour has yet to be carefully investigated while freezers approach narrow spaces, thus the overall objective of this study was to explore the interaction between cognitive and sensory-perceptual influences on FOG. In experiment #1, if cognitive load is the underlying factor leading to FOG, then one might expect that a dual-task would elicit FOG episodes even in the presence of visual cues, since the load on attention would interfere with utilization of visual cues. Alternatively, if visual cues alleviate gait despite performance of a dual-task, then it may be more probable that sensory mechanisms are at play. In compliment to this, the aim of experiment#2 was to further challenge the sensory systems, by removing vision of the lower-limbs and thereby forcing participants to rely on other forms of sensory feedback rather than vision while walking toward the narrow space. Spatiotemporal aspects of gait, percentage of gaze fixation frequency and duration, as well as skin conductance levels were measured in freezers and non-freezers across both experiments. Results from experiment#1 indicated that although freezers and non-freezers both walked with worse gait while performing the dual-task, in freezers, gait was relieved by visual cues regardless of whether the cognitive demands of the dual-task were present. At baseline and while dual-tasking, freezers demonstrated a gaze behaviour that neglected the doorway and instead focused primarily on the pathway, a strategy that non-freezers adopted only when performing the dual-task. Interestingly, with the combination of visual cues and dual-task, freezers increased the frequency and duration of fixations toward the doorway, compared to non-freezers. These results suggest that although increasing demand on attention does significantly deteriorate gait in freezers, an increase in cognitive demand is not exclusively responsible for freezing (since visual cues were able to overcome any interference elicited by the dual-task). When vision of the lower limbs was removed in experiment#2, only the freezers' gait was affected. However, when visual cues were present, freezers' gait improved regardless of the dual-task. This gait behaviour was accompanied by greater amount of time spent looking at the visual cues irrespective of the dual-task. Since removing vision of the lower-limbs hindered gait even under low attentional demand, restricted sensory feedback may be an important factor to the mechanisms underlying FOG.

Most systems of interest in today's world are highly structured and highly interactive. They cannot be reduced to simple components without losing a great deal of their system identity. Network thermodynamics is a marriage of classical and non-equilibrium thermodynamics along with network theory and kinetics to provide a practical framework for handling these systems. The ultimate result of any network thermodynamic model is still a set of state vector equations. But these equations are built in a new informative way so that information about the organization of the system is identifiable in the structure of the equations. The domain of network thermodynamics is all of physical systems theory. By using the powerful circuit simulator, the Simulation Program with Integrated Circuit Emphasis (SPICE), as a general systems simulator, any highly non-linear stiff system can be simulated. Furthermore, the theoretical findings of network thermodynamics are important new contributions. The contribution of a metric structure to thermodynamics compliments and goes beyond other recent work in this area. The application of topological reasoning through Tellegen's theorem shows that a mathematical structure exists into which all physical systems can be represented canonically. The old results in non-equilibrium thermodynamics due to Onsager can be reinterpreted and extended using these new, more holistic concepts about systems. Some examples are given. These are but a few of the many applications of network thermodynamics that have been proven to extend our capacity for handling the highly interactive, non-linear systems that populate both biology and chemistry. The presentation is carried out in the context of the recent growth of the field of complexity science. In particular, the context used for this discussion derives from the work of the mathematical biologist, Robert Rosen.

BACKGROUND

The monoclonal antibodies (mAbs) that target the epidermal growth factor receptor (EGFR) had expanded the range of treatment options for metastatic colorectal cancer. However, such type of treatment was shown to be ineffective if there is K-ras mutation. In most previous studies K-ras gene mutation was mainly assessed by PCR.

OBJECTIVE

Our work is designed to detect K-ras protein expression by immunohistochemistry (IHC) aiming to reach a preliminary method that could be confirmed by PCR and considered an alternative way for the detection of K-ras aberration. We are also aiming to find a relation between K-ras protein expression and K-ras gene mutation.

METHODS

Paraffin embedded tissue samples from 26 metastatic colorectal cancer (mCRC) patients were analyzed for K-ras protein expression by IHC using Rap1A polyclonal antibody. Staining patterns were subjectively assessed and correlated with clinicopathological features. The results were statistically evaluated using the Chi-square test.

RESULTS

K-ras cytoplasmic positivity was observed in 42.3% of cases. The positivity was either strong in 26.9% or moderate in 15.4%. With respect to adenocarcinoma variants, 50% of cases were positive for K-ras protein expression while all mucinous and signet ring types were negative. The positivity was noted in 50% of moderately differentiated GII colorectal carcinomas as compared with 38.9% in poorly differentiated GIII. Positive staining was observed in 40% of cases with positive lymph node metastasis while in the absence of nodal metastasis the positivity was 45.5%. No significant correlation was found between clinicopathological parameters and K-ras staining results.

CONCLUSIONS

IHC may compliment PCR in the detection of K-ras mutation.

Brain tumours are a diverse group of neoplasms that continue to present a formidable challenge in our attempt to achieve curable intervention. Our conceptual framework of human brain cancer has been redrawn in the current decade. There is a gathering acceptance that brain tumour formation is a phenotypic outcome of dysregulated neurogenesis, with tumours viewed as abnormally differentiated neural tissue. In relation, there is accumulating evidence that brain tumours, similar to leukaemia and many solid tumours, are organized as a developmental hierarchy which is maintained by a small fraction of cells endowed with many shared properties of tissue stem cells. Proof that neurogenesis persists throughout adult life, compliments this concept. Although the cancer cell of origin is unclear, the proliferative zones that harbour stem cells in the embryonic, post-natal and adult brain are attractive candidates within which tumour-initiation may ensue. Dysregulated, unlimited proliferation and an ability to bypass senescence are acquired capabilities of cancerous cells. These abilities in part require the establishment of a telomere maintenance mechanism for counteracting the shortening of chromosomal termini. A strategy based upon the synthesis of telomeric repeat sequences by the ribonucleoprotein telomerase, is prevalent in approximately 90% of human tumours studied, including the majority of brain tumours. This review will provide a developmental perspective with respect to normal (neurogenesis) and aberrant (tumourigenesis) cellular turnover, differentiation and function. Within this context our current knowledge of brain tumour telomere/telomerase biology will be discussed with respect to both its developmental and therapeutic relevance to the hierarchical model of brain tumourigenesis presented by the cancer stem cell paradigm.

The arsenic (As) solid-state speciation (i.e., oxidation state, precipitates, and adsorption complexes) is one of the most important factors controlling dissolved As concentrations at As contaminated sites. In this case study, two representative subsurface samples (i.e., oxidized and semi-reduced sites) from former lead arsenate contaminated soils in the northeastern United States were chosen to investigate the effects of aging on As retention mechanisms using multiscale spectroscopic techniques. X-ray powder diffraction (XRD), synchrotron based microfocused (micro) XRD, in situ micro-synchrotron based X-ray fluorescence spectroscopy (SXRF), and micro-X-ray absorption near edge structure (XANES) spectroscopy were used to compliment the final bulk X-ray absorption spectroscopy (XAS) analyses. In the sample from an oxic area, As is predominantly (approximately 71%) present as As(V) adsorbed onto amorphous iron oxyhydroxides with a residue (approximately 29%) of an original contaminant, schultenite (PbHAsO4). Contrarily, there is no trace of schultenite in the sample from a semi-reduced area. Approximately 25% of the total As is present as adsorbed phases on amorphous iron oxyhydroxide and amorphous orpiment (As2S3). The rest of the fractions (approximately 46%) were identified as As(V)-Ca coprecipitates. This study shows that aging effects can significantly alter the original chemical constituent (schultenite) in soils, resulting in multi and site-specific As solid-state speciation. The variability in spatial and temporal scale may be important in assessing the environmental risk and in developing in situ remediation technologies.

Two genetic models that could explain all of the current data are depicted in Figure 4, although it should be stressed that proof of any model will require additional genetic analyses. The first model (Model A) indicates that one or more loci controlling responsiveness to TPA are also responsible for directly controlling responsiveness to other classes of skin tumor promoters such as BzPo and Chr. We have called this locus the Pms locus (for skin tumor promotion sensitivity). The differences between compounds in the magnitude of their promoting ability may reside in the inability to activate a full set or compliment of Pms loci. Genetic differences may reside in a critical Pms locus that is necessary for tumor promotion by all chemical promoters. Alternatively, the current data could be interpreted as showing that different genes responsible for high sensitivity to promotion by diverse promoting agents act on a pathway(s) common to promotion in mouse epidermis (Model B). In this case, the Pms locus would represent a common biochemical/molecular pathway where different responses mediated by different types of promoters ultimately converge and lead to the process of tumor promotion in mouse skin. Directly testing either of the above models will require analyses of progeny from appropriate segregating crosses among the various stocks and strains used in the present study. Model B could help explain several experimental observations. First, SSIn mice, while still retaining a fairly high sensitivity to skin tumor promotion with Chr relative to other inbred strains (i.e., DBA/2, C57BL/6), have lost their increased sensitivity to this anthrone derivative relative to SENCAR mice. SSIn were developed through a process of inbreeding starting with the current outbred SENCAR and employing a selection scheme using DMBA initiation and TPA promotion similar to that originally devised by Boutwell (1964). Second, C57BL/6 mice, although relatively resistant to TPA, chrysarobin and BzPo, are somewhat peculiar in their high resistance to standard promotion protocols using TPA (DiGiovanni et al., 1991). Indirectly, these observations suggest that different genes may regulate some responses to particular types of promoting agent. For example, perhaps the induction of a oxidant response by phorbol esters would represent a specific response to this class of tumor promoters. A testable prediction from these observations is that it may be possible to selectively breed for mouse lines more sensitive and/or resistant to specific classes of promoting agents.

Several strains of Corynebacterium and Brevibacterium are known for their ability to secrete large amounts of amino acids, especially L-glutamate. We focused on the mechanism of L-glutamate secretion triggered by a detergent, namely polyoxyethylenesorbitan monopalmitate (PESP). A mutant strain, AJ11060, derived from Brevibacterium lactofermentum ATCC 13869 indicates the sensitivity to PESP. A multicopy suppresser gene that compliments the sensitivity of AJ11060 to the detergent was derived from a gene library of B. lactofermentum AJ12036. A 2855-bp DNA fragment was cloned and sequenced. An open reading frame was found that coded for the rescuer gene of the sensitivity to PESP of AJ11060 and was designated dtsR. The expression of the dtsR gene in B. lactofermentum was confirmed by using anti-DtsR antibody. The deduced DtsR protein indicated significant homology with some biotin enzymes such as the beta chain of propionyl-CoA carboxylase from rat (48.3%) and human (48.7%), or a 12S chain of methylmalonyl-CoA carboxyltransferase from Propionibacterium freudenreichii (43.1%).

1. The present study assessed the potential antidepressant action of gepirone hydrochloride, an azapirone serotonin (5-HT1A) partial agonist in patients with major depression. 2. Overall, gepirone demonstrated a significant antidepressant activity within the entire patient group (p less than 0.001). However, when subjects were stratified based upon the presence or absence of DSM III-R melancholic features, the melancholic depressives showed little change in weekly depression ratings compared to patients without melancholic symptoms (p less than 0.001). 3. Similarly, patients who were more severely ill at the pretreatment period had less improvement compared to those with more modest illness severity (p less than 0.001). 4. These observations compliment those of prior studies suggesting antidepressant activity for gepirone. 5. However, a consistent efficacy comparable to conventional neuronal reuptake inhibitor antidepressants remains to be established in patients with more severe depression characterized by melancholic features.

OBJECTIVE

Situation awareness (SA) is a vital construct for decision making in intense, dynamic environments such as trauma resuscitation. Human patient simulation (HPS) allows for a safe environment where individuals can develop these skills. Trauma resuscitation is performed by multidisciplinary teams that are traditionally difficult to globally assess. Our objective was to create and validate a novel tool to measure SA in multidisciplinary trauma teams using a HPS--the Team Situation Awareness Global Assessment Technique (TSAGAT).

METHODS

Memorial University Simulation Centre.

METHODS

Using HPS, 4 trauma teams completed 2 separate trauma scenarios. Student, junior resident, senior resident, and attending staff teams each had 3 members (trauma team leader, nurse, and airway manager). Individual SAGATs were developed by experts in each respective field and contained shared and complimentary knowledge questions. Teams were assessed with SAGAT in real time and with traditional checklists using video review. TSAGAT was calculated as the sum of individual SAGAT scores and was compared with the traditional checklist scores.

RESULTS

Shared, complimentary, and TSAGAT scores improved with increasing team experience. Differences between teams for TSAGAT and complimentary knowledge were statistically significant (p < 0.05). Mean checklist differences between teams also reached statistical significance (p < 0.05). TSAGAT scores correlated strongly with traditional checklist scores (Pearson correlation r = 0.996). Interrater reliability for the checklist tool was high (Pearson correlation r = 0.937).

CONCLUSIONS

TSAGAT is the first valid and reliable assessment tool incorporating SA and HPS for multidisciplinary team performance in trauma resuscitation. TSAGAT could compliment or improve on current assessment methods and curricula in trauma and critical care and provides a template for team assessment in other areas of surgical education.

The current study compared the effects of reward anticipation on task performance in children and adolescents (8-16 years old) using monetary and various social rewards. Eighty-five typically developing children undertook the Monetary Incentive Delay (MID) task. Of these 44 also undertook the Social Incentive Delay (SID-basic) task where social reward was operationalized as a smiling face and spoken compliments. Forty-one children participated in the SID-plus where points were added to a pictogram with written compliments. In a preparatory validation study participants were asked howmuch they liked the SID-basic rewards.Results showed that there was an effect of reward size on accuracy and RT in both the MID task and SID-plus, but not SID-basic. Subjective value of the SID-basic rewards was rated higher with hypothesized increasing reward intensity. In conclusion, although the social rewards in SID-basic were liked by children andadolescents in the validation study, they had no effect on the behaviour. Only when points were added (SID-plus), anticipated social reward affected task performance. Thus our results highlight (i) the difference between likeability andreinforcing quality and (ii) the need for a quantifiable element to rewards for themto be reinforcing for children.

BACKGROUND

We showed that subjects with cerebral palsy had greater transverse and frontal plane hip and knee motion, increased duration of muscle activity, increased cocontraction, and decreased efficiency during recumbent cycling than subjects with typical development. However, it is also important to understand the forces exerted on the pedals. The purpose of this report was to compare pedal forces during cycling between adolescents with and without cerebral palsy.

METHODS

Ten subjects (3 male, 7 female) with spastic diplegic or quadriplegic cerebral palsy (15.6 years, SD 1.8) and 10 subjects (3 male, 7 female) with typical development (14.9 years, SD 1.4) cycled on a stationary recumbent cycle at 30 and 60 revolutions per minute if able. Three-dimensional piezoelectric force transducers measured pedal forces. Data were analyzed using two-way ANOVAs.

RESULTS

Subjects with cerebral palsy spent a smaller percentage (P<.001, r2=.09, power=1.0) of the revolution applying positive force (pushing into the pedal during the extension phase) and a greater percentage (P<.001, r2=.09, power=1.0) of the revolution applying negative force (pulling away from the pedal during the flexion phase). There was no effect of cadence and no interaction effect.

CONCLUSIONS

These findings compliment our earlier findings of altered joint kinematics and muscle activity indicating that subjects with cerebral palsy and typical development have different cycling strategies. Methods to increase the duration of the positive force may allow subjects with CP to cycle more successfully and cycle vigorously enough to reach a heart rate necessary for improving fitness.

Previously thought "junk" DNA, short tandem repeats consisting of (GATA)n, or its compliment, were found in varied metazoan eukaryotic genomes but were rare in yeast and bacterial genomes. The (GATA)n sequence was found in cDNAs encoding mRNAs with known functions. At least 16 of 18 such transcripts encode membrane-associated proteins including: plasma membranes, synapses, mitochondrial membranes, nuclear envelopes, and brush border membranes. Flanking sequences were diverse but (GATA)n sequences clustered around 500 bases from stop codons. The (GATA)n sequences occurred in both orientations and showed constrained polymorphism. In sets of splice variants with and without (GAUA)n, the STR containing transcripts were the most abundant. These observations suggest that (GATA)n sequences probably function. In many cases, the function may be to encode post-transcriptional signals for mRNAs encoding membrane-associated proteins.

Color duplex ultrasound testing has evolved to be a clinically useful modality to diagnose chronic mesenteric ischemia caused by visceral artery origin atherosclerosis. Testing requires expertise in ultrasound imaging, visceral artery hemodynamics, and duplex scan interpretation. Patient can be accurately screened for severe stenosis or occlusion involving celiac, superior mesenteric, or inferior mesenteric arteries. Duplex testing can also evaluate functional patency following visceral bypass grafting procedures or endovascular stent-angioplasty. The focus of duplex surveillance after visceral artery intervention is to identify severe repair site stenosis, which can develop with symptoms of gut ischemia. Visceral duplex testing of a bypass graft or stent-angioplasty site that shows peak systolic velocities >300 cm/s with end-diastolic velocities >50 to 70 cm/s, or a decreased graft velocity peak systolic velocity <40 cm/s should be considered for interrogation using angiography to confirm or exclude severe (>70%) stenosis. Duplex testing after surgical or endovascular visceral interventions is a screening study, which compliments clinical follow-up by aiding the vascular surgeon in timely identification of visceral repairs that have developed a progressive, high-grade stenosis.

Military experience and recent in vitro laboratory data provide a biological rationale for whole-blood use in the treatment of exsanguinating hemorrhage and have renewed interest in the reintroduction of fresh whole blood and cold-stored whole blood to patient care in austere environments. There is scant evidence to support, in a field environment, that a whole blood-based resuscitation strategy is superior to a crystalloid/colloid approach even when augmented by a limited number of red blood cell (RBC) and plasma units. Recent retrospective evidence suggests that, in this setting, resuscitation with a full compliment of RBCs, plasma, and platelets may offer an advantage, especially under conditions where evacuation is delayed. No current evacuation system, military or civilian, is capable of providing RBC, plasma, and platelet units in a prehospital environment, especially in austere settings. As a result, for the vast minority of casualties, in austere settings, with life-threatening hemorrhage, it is appropriate to consider a whole blood-based resuscitation approach to provide a balanced response to altered hemostasis and oxygen debt, with the goal of reducing the risk of death from hemorrhagic shock. To optimize the successful use of fresh whole blood/cold-stored whole blood in combat field environments, proper planning and frequent training to maximize efficiency and safety will be required. Combat medics will need proper protocol-based guidance and education if whole-blood collection and transfusion are to be successfully and safely performed in austere environments. In this article, we present the Norwegian Naval Special Operation Commando unit-specific remote damage control resuscitation protocol, which includes field collection and transfusion of whole blood. This protocol can serve as a template for others to use and adjust for their own military or civilian unit-specific needs and capabilities for care in austere environments.

Emerging evidence suggests that central synaptic inputs onto motor neurons (MNs) play an important role in developmental regulation of the final number of MNs and their muscle innervation for a particular motor pool. Here, we describe the effect of genetic deletion of glycinergic neurotransmission on single MN structure and on functional excitatory and inhibitory inputs to MNs. We measured synaptic currents in E18.5 hypoglossal MNs from brain slices using whole-cell patch-clamp recording, followed by dye-filling these same cells with Neurobiotin, to define their morphology by high-resolution confocal imaging and 3D reconstruction. We show that hypoglossal MNs of mice lacking gephyrin display increased dendritic arbor length and branching, increased spiny processes, decreased inhibitory neurotransmission, and increased excitatory neurotransmission. These findings suggest that central glycinergic synaptic activity plays a vital role in regulating MN morphology and glutamatergic central synaptic inputs during late embryonic development.

UNASSIGNED

MNs within the brainstem and spinal cord are responsible for integrating a diverse array of synaptic inputs into discrete contractions of skeletal muscle to achieve coordinated behaviors, such as breathing, vocalization, and locomotion. The last trimester in utero is critical in neuromotor development, as this is when central and peripheral synaptic connections are made onto and from MNs. At this time-point, using transgenic mice with negligible glycinergic postsynaptic responses, we show that this deficiency leads to abnormally high excitatory neurotransmission and alters the dendritic architecture responsible for coherently integrating these inputs. This study compliments the emerging concept that neurodevelopmental disorders (including autism, epilepsy, and amyotrophic lateral sclerosis) are underpinned by synaptic dysfunction and therefore will be useful to neuroscientists and neurologists alike.

Stem cells provide a continuous supply of committed progenitor cells for the process of spermatogenesis. In rodents, stem cells have been identified as single, undifferentiated type A spermatogonia. The rate of stem cell division has not been definitively determined because of difficulty in locating stem cells among a normal compliment of germ cells. The testicular toxicant 2,5-hexanedione (2,5-HD) induces irreversible testicular atrophy with only Sertoli cells and spermatogonia remaining after injury. Stem cell kinetics could be assessed in this toxicant model because of the absence of most mature germ cells. It is also not known if 2,5-HD-exposed rats possess an active stem spermatogonia population. Charles River CD rats were exposed to 1% 2,5-HD in drinking water for 5 wk. At 7 or 35 wk following toxicant exposure, rats were exposed to bromodeoxycytidine continuously via Alzet mini-pumps for 1-28 days. Serial cross sections of testis were used to identify single stem spermatogonia and to determine whether the cells were positive or negative for bromodeoxyuridine incorporation. We obtained a continuous labeling index for stem cells from rats 7 and 35 wk after 2,5-HD exposure and found that stem cells had a cell cycle time of approximately 8-14 days at both time points after toxicant exposure. In conclusion, we have developed a method for the assessment of stem cell kinetics and verified the presence of an actively dividing stem cell population in irreversibly injured testes.

The epithelial sodium channel (ENaC) is a principal site for sodium reabsorption and as such may participate importantly in blood pressure (BP) regulation. Amiloride, a direct inhibitor of ENaC, characteristically has mild antihypertensive properties, consistent with ENaC having more minor influences on BP regulation. Counter-regulatory influences may, however, prevent amiloride from effectively lowering BP. Aldosterone secretion is known to increase in response to the reduced sodium reabsorption that follows amiloride inhibition of ENaC, and because aldosterone upregulates ENaC function, we considered the possibility that secondary hyperaldosteronism mitigates the ability of amiloride to reduce BP. In the present study, the BP responses to amiloride (5 mg per day), spironolactone (25 mg per day), the combination of the 2 drugs, and placebo were studied in healthy normotensive subjects. Over 4 weeks of treatment, the combination of amiloride and spironolactone lowered systolic BP by 4.6+/-1.6 (mean+/-SEM) mm Hg (P=0.022) and diastolic BP by 2.2+/-1.2 mm Hg (P=0.30), whereas either drug alone had no significant effect on BP. The findings suggest that the 2 drugs with different modes of action-amiloride, a direct inhibitor of ENaC, and spironolactone, a mineralocorticoid receptor antagonist-may compliment each other's ability to inhibit ENaC and thereby reduce sodium reabsorption to a point at which BP decreases. On the other hand, we cannot rule out that the BP response resulted from the greater dose of total drug. The lowering of BP with small doses of inhibitors of ENaC serves as additional evidence for the importance of ENaC to the tonic maintenance of BP.

OBJECTIVE

Clinicians identify seizure onset zones (SOZs) for resection in an attempt to localize the epileptogenic zone (EZ), which is the cortical tissue that is indispensible for seizure generation. An automated system is proposed to objectively localize this EZ by identifying regions of interest (ROIs).

METHODS

Intracranial electroencephalogram recordings were obtained from seven patients presenting with extratemporal lobe epilepsy and the interaction between neuronal rhythms in the form of phase-amplitude coupling was investigated. Modulation of the amplitude of high frequency oscillations (HFOs) by the phase of low frequency oscillations was measured by computing the modulation index (MI). Delta- (0.5-4 Hz) and theta- (4-8 Hz) modulation of HFOs (30-450 Hz) were examined across the channels of a 64-electrode subdural grid. Surrogate analysis was performed and false discovery rates were computed to determine the significance of the modulation observed. Mean MI values were subjected to eigenvalue decomposition (EVD) and channels defining the ROIs were selected based on the components of the eigenvector corresponding to the largest eigenvalue. ROIs were compared to the SOZs identified by two independent neurologists. Global coherence values were also computed.

RESULTS

MI was found to capture the seizure in time for six of seven patients and identified ROIs in all seven. Patients were found to have a poorer post-surgical outcome when the number of EVD-selected channels that were not resected increased. Moreover, in patients who experienced a seizure-free outcome (i.e., Engel Class I) all EVD-selected channels were found to be within the resected tissue or immediately adjacent to it. In these Engel Class I patients, delta-modulated HFOs were found to identify more of the channels in the resected tissue compared to theta-modulated HFOs. However, for the Engel Class IV patient, the delta-modulated HFOs did not identify any of the channels in the resected tissue suggesting that the resected tissue was not appropriate, which was also suggested by the Engel Class IV outcome. A sensitivity of 75.4% and a false positive rate of 15.6% were achieved using delta-modulated HFOs in an Engel Class I patient.

CONCLUSIONS

LFO-modulated HFOs can be used to identify ROIs in extratemporal lobe patients. Moreover, delta-modulated HFOs may provide more accurate localization of the EZ. These ROIs may result in better surgical outcomes when used to compliment the SOZs identified by clinicians for resection.

BACKGROUND

From the 1970s till the mid 1990s, hepatitis B was the most common etiological factor for hepatocellular carcinoma (HCC) in Pakistan. Afterwards, a shift in HCC etiology was observed with a steady rise in hepatitis C virus (HCV) related HCC cases. HCV-3a, which is the most prevalent genotype, is also most frequent in HCV related HCC. There was an increase in the proportion of non-B non-C (NBNC) HCC cases as well, which might be attributed to an increase in non-alcoholic fatty liver disease.

METHODS

The age-standardized rate for HCC is 7.64/100 000 in males and 2.8/100 000 in females. Male to female ratio is 3.6:1. Usual age of presentation is in the fifth and sixth decade. Most patients present with advanced disease, as they are not in a regular surveillance program. This is more so for patients with NBNC chronic liver disease. As many sonologists in Pakistan are practicing without sufficient training to pick up early lesions, alpha-fetoprotein is still recommended to compliment ultrasound in the surveillance of HCC.

RESULTS

Majority of HCC patients present with nonresectable disease. Interventions such as transarterial chemoembolization, radiofrequency ablation, resection and chemotherapy including sorafenib are available in selected centers. Pakistan appears to be in an area of intermediate endemicity for HCC. There is a need for population based epidemiological studies to estimate the exact disease burden.

CONCLUSIONS

Measures to prevent the spread of hepatitis C and B can slow down the epidemic rise in the incidence of HCC in the coming decades. There is a need to implement a proper surveillance program to identify HCC cases at an early stage.

The practical application of rigid, macro-porous organic polymer and silica based monolithic stationary phases as separation media has been described in the literature since 1992 and 1996, respectively. Today these materials are extensively used in chromatography and electrochromatography and several detailed reviews appear annually describing these materials, their synthesis and application. To compliment these publications, this review focuses upon the less commonly utilised materials for monolith synthesis, both those that have already been applied within separation science, and those that have found applications elsewhere, such as catalysis and water filtration, but have the clear potential to be explored as novel stationary phases in the near future. For the purpose of the review monoliths formed from these various alternative materials will be termed 'Exotic Monoliths', as these new substrates in many cases have only just begun to be explored for chromatographic separations, and in many instances have unusual and highly selective surface chemistries, which are attractive in terms of broadening the choice of monolithic materials for separation science. An extensive range of monolithic materials based on the following elements and their compounds (mostly oxides) are covered: Zr, Ti, Al, Hf, C, Au, Ag, Ce, Ge and hydroxyapatite, together with their relevant properties, methods of synthesis, and current and potential applications in separation science.

Recognition of gastric epithelial dysplasia, although a key to cancer prevention, can be challenging. In this study, we evaluated whether Lgl2 can serve as a marker of gastric foveolar-type dysplasia. Since atypical protein kinase C (aPKC) is a partner of Lgl2 in the control of apical-basal polarity we also investigated whether aPKC-zeta can compliment Lgl2 as a marker of dysplasia. Routinely processed specimens included 64 normal mucosa, 35 reactive gastropathies, 31 chronic gastritides, 65 gastric dysplasias (25 foveolar; 40 adenomatous), and 34 gastric adenocarcinomas. Twenty (80%) foveolar-type dysplasias showed absence of Lgl2 immunoreactivity, while normal basolateral expression of Lgl2 was consistently seen in normal gastric epithelium (n=20) and chronic gastritis (n=22; p<0.00001). Loss of Lgl2 was similar in the groups with low-grade and high-grade foveolar-type dysplasia, 79% and 83%, respectively. Linear apical anti-aPKC-zeta immunoreactivity was consistently present in the normal epithelium and was preserved in 91% of reactive gastropathies and 87% of chronic gastritides. In contrast, loss of apical aPKC-zeta staining was observed in 47% and 65% of low-grade dysplasias of foveolar and adenomatous types, respectively (p<0.005) and in nonsignificantly higher percentage of high-grade dysplasias. Apical aPKC-zeta staining was lost in 97% of gastric adenocarcinomas. Our data suggest a role of Lgl2 immunohistochemistry as an adjunct in the diagnosis of foveolar-type gastric dysplasia. aPKC-zeta had moderate sensitivity as a marker of gastric dysplasia and additional studies are needed to establish its role in the diagnosis of dysplasia.

High-resolution manometry (HRM) allows nuanced evaluation of esophageal motor function, and more accurate evaluation of lower esophageal sphincter (LES) function, in comparison with conventional manometry. Pathophysiologic correlates of gastroesophageal reflux disease (GERD) and esophageal peristaltic performance are well addressed by this technique. HRM may alter the surgical decision by assessment of esophageal peristaltic function and exclusion of esophageal outflow obstruction before antireflux surgery. Provocative testing during HRM may assess esophageal smooth muscle peristaltic reserve and help predict the likelihood of transit symptoms following antireflux surgery. HRM represents a continuously evolving new technology that compliments the evaluation and management of GERD.

The N-terminal domain of phosphoglycerate kinase (N-PGK) and domain 1 of the T-cell adhesion protein CD2 (CD2.d1) fold through rapidly formed and transiently populated intermediate states in reactions which have no kinetic complications arising from proline isomerization or disulfide bonding. We have evaluated the thermodynamic parameters (DeltaCp, change in heat capacity; DeltaS, entropy change; DeltaH, enthalpy change) for each experimentally accessible step in these folding reactions. Despite their different topologies and amino acid compositions, the individual steps [U-I (unfolded to intermediate state), I-t (intermediate to major transition state), and t-F (transition state to the fully folded state)] have closely similar qualitative properties in the two proteins. For both, the heat capacity changes are proportional to m-value changes (Deltam) for every step in the reaction, but the ratio DeltaCp/Deltam is lower for N-PGK, presumably owing to a much larger compliment of aromatic amino acids in the core. According to measurements of DeltaCp and Deltam, the I-states are highly condensed (65-70% for N-PGK and 40-45% dehydrated for CD2.d1), yet the changes in entropy in the U-to-I transition are small, showing that the entropy gained from desolvation must be balanced by that lost in ordering the chain. The high degree of conformational order in the I-state, implied by these measurements, is mirrored by the extensive, native secondary structure revealed by amide exchange measurements [Hosszu, L. L. P., et al. (1997) Nat. Struct. Biol. 4, 801-804; Parker, M. J., et al. (1997) Biochemistry 36, 13396-13405]. At 25 degreesC the transition state barrier has an entirely enthalpic origin, the entropic contribution being favorable. The latter observation implies that, during the consolidation of structure occurring in the I-to-F step, further dehydration (positive DeltaS) precedes side-chain locking (negative DeltaS). Only after the transition state is surmounted do we see a net entropic penalty arising from the widespread ordering of side chains.