Toward biophysical markers of depression vulnerability.

A major difficulty with treating psychiatric disorders is their heterogeneity: different neural causes can lead to the same phenotype. To address this, we propose describing the underlying pathophysiology in terms of interpretable, biophysical parameters of a neural model derived from the electroencephalogram. We analyzed data from a small patient cohort of patients with depression and controls. Using DCM, we constructed biophysical models that describe neural dynamics in a cortical network activated during a task that is used to assess depression state. We show that biophysical model parameters are biomarkers, that is, variables that allow subtyping of depression at a biological level. They yield a low dimensional, interpretable feature space that allowed description of differences between individual patients with depressive symptoms. They could capture internal heterogeneity/variance of depression state and achieve significantly better classification than commonly used EEG features. Our work is a proof of concept that a combination of biophysical models and machine learning may outperform earlier approaches based on classical statistics and raw brain data.

Accuracy of Software-Based Three-Dimensional Root Canal Length Measurements Using Cone-Beam Computed Tomography.

OBJECTIVE: This study aims to evaluate the accuracy of three-dimensional root canal length measurements performed by dentists with different experience levels using a special software based on cone beam com-puted tomography (CBCT). METHODS: A CBCT scan of an artificial resin maxillary molar was used to train dentists (n=65) in using the software (3D Endo, DentsplySirona, Ballaigues, Switzerland) as part of a continuing education course. At the beginning, each participant completed a questionnaire on endodontic and CBCT experiences. After com-prehensive instructions, each participant performed an entire three-dimensional treatment plan by tracing the root canal anatomy between the apical foramen and the center of the canal orifice and simulating a straight-line access. The final root canal length was indicated after the virtual rubber stop of a simulated instrument was adapted to the adjoining cusp. To evaluate the individual accuracy in terms of trueness and precision, differences between the three-dimensional planning and the actual root canal length (ARCL) were calculated, and statistically analyzed. RESULTS: Mean absolute differences between the measurements with the 3D Endo™ software (n=260) and the ARCL were 0.30±0.22 mm. All measurements were within a limit of ±1 mm. The accuracy of root canal length measurements was significantly influenced by the type of root canal (p<0.0001). The smallest devia-tions were observed for the palatal root canal (0.18±0.13 mm), followed by the mesiobuccal (0.26±0.22 mm), the distobuccal (0.32±0.17 mm), and the second mesiobuccal root canal (0.46±0.24 mm). CONCLUSION: Within the limitations of this study, the 3D Endo software enables reproducible and accurate root canal length measurements as part of a three-dimensional endodontic treatment plan. However, mea-surements should always be clinically verified, as root canal morphology has a statistically significant influence.

Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery-VMI): lessons from exploration of cultural variations in visual-motor integration performance of preschoolers.

BACKGROUND: Visual-motor integration (VMI) is important in children's development because it is associated with the performance of many functional skills. Deficits in VMI have been linked to difficulties in academic performance and functional tasks. Clinical assessment experience of occupational therapists in Singapore suggested that there is a potential difference between the VMI performance of Singaporean and American children. Cross-cultural studies also implied that culture has an influence on a child's VMI performance, as it shapes the activities that a child participates in. The purpose of this study was to (1) explore if there was a difference between the VMI performance of Singaporean and American preschoolers, and (2) determine if there were ethnic differences in the VMI performance of Singaporean preschoolers. METHODS: The Beery-VMI, which was standardized in America, is commonly used by occupational therapists in Singapore to assess the VMI ability of children. We administered the Beery-VMI (fifth edition) full form test (excluding the supplemental tests) to 385 preschoolers (mean age = 63.3 months) from randomly selected schools in Singapore. We compared the scores of Singaporean preschoolers with those of the American standardization norms using the one-sample t-test. Scores of different ethnic groups among the Singapore population were also compared using a one-way anova, followed by the Bonferroni post-hoc test. RESULTS: Singaporean preschoolers and the standardization sample of American children performed significantly differently in all age groups (P < 0.05). Among the Singapore population, the scores were also significantly different (P < 0.05) between the (i) Chinese and Malay and (ii) Chinese and Indians ethnic groups. CONCLUSION: Preschoolers from different cultural and ethnic groups had different VMI performance. Certain cultural beliefs and practices may affect VMI performance. Clinicians should exercise caution when using an assessment in communities and cultures outside the ones on which it was standardized.

Perinatal autopsy rates at the University Hospital of the West Indies: 2002-2008.

OBJECTIVES: High perinatal autopsy rates are necessary for institutional management protocols and national policy-making. This study reviews perinatal autopsy rates and factors affecting these rates at the University Hospital of the West Indies. METHOD: All perinatal deaths (stillborn infants > or = 24 weeks gestation or 500 g; early neonatal deaths ie 0-7 days old) at the University Hospital of the West Indies, between January 2002 and December 2008, were reviewed retrospectively, using the annual perinatal audit records. The annual autopsy rates were calculated and the reasons why autopsies were not done examined. RESULTS: The average stillbirth (SB) autopsy rate was 59.6% (range 51.9 - 76.7%), while that for early neonatal deaths (ENDs) was 47.9% (range 34.4 - 63.2), with an overall average perinatal autopsy rate of 54.0% (range 42.2 - 62.2). Autopsies were requested in 79.3% and 51.7% of SBs and ENDs, respectively. Of those requested, 81.7% were done (75.2% stillbirths; 92.5% ENDs). In the ENDs, failure to request an autopsy was predominantly noted in premature infants weighing < 1000 g (75.2% of those not requested). In stillbirths, the reasons for failure to request were largely unknown with failure to gain permission accounting for only 20.3% of these cases. CONCLUSIONS: The average annual perinatal autopsy rate at the University Hospital of the West Indies between 2002 and 2008 was 54.0%. This is below the internationally recommended rate of 75%. Failure to request an autopsy was the most significant factor contributing to this. The reasons for this are not entirely clear and require further study.

Perinatal autopsy rates at the University Hospital of the West Indies: 2002-2008 / Tasas de autopsia perinatal en el Hospital Universitario de West Indies: 2002-2008

OBJECTIVES: High perinatal autopsy rates are necessary for institutional management protocols and national policy-making. This study reviews perinatal autopsy rates and factors affecting these rates at the University Hospital of the West Indies. METHOD: All perinatal deaths (stillborn infants > 24 weeks gestation or 500 g; early neonatal deaths ie 0-7 days old) at the University Hospital of the West Indies, between January 2002 and December 2008, were reviewed retrospectively, using the annual perinatal audit records. The annual autopsy rates were calculated and the reasons why autopsies were not done examined. RESULTS: The average stillbirth (SB) autopsy rate was 59.6% (range 51.9 - 76.7%), while that for early neonatal deaths (ENDs) was 47.9% (range 34.4 - 63.2), with an overall average perinatal autopsy rate of 54.0% (range 42.2 - 62.2). Autopsies were requested in 79.3% and 51.7% of SBs and ENDs, respectively. Of those requested, 81.7% were done (75.2% stillbirths; 92.5% ENDs). In the ENDs, failure to request an autopsy was predominantly noted in premature infants weighing < 1000 g (75.2% of those not requested). In stillbirths, the reasons for failure to request were largely unknown with failure to gain permission accounting for only 20.3% of these cases. CONCLUSIONS: The average annual perinatal autopsy rate at the University Hospital of the West Indies between 2002 and 2008 was 54.0%. This is below the internationally recommended rate of 75%. Failure to request an autopsy was the most significant factor contributing to this. The reasons for this are not entirely clear and require further study.

OBJETIVOS: Las altas tasas autopsia perinatal son necesarias para los protocolos institucionales de tratamiento, y el establecimiento de políticas a nivel nacional. Este estudio examina las tasas de autopsia perinatal y los factores que afectan estas tasas, en el Hospital Universitario de West Indies. MÉTODO: Todas las muertes perinatales (mortinatos > 24 semanas de gestación o 500 g; muertes neonatales tempranas, es decir, 0-7 días de nacido) en el Hospital Universitario de West Indies, entre el 2002 de enero y el 2008 de diciembre, fueron sometidas a examen retrospectivo, usando los registros de auditoría perinatales anuales.Las tasas de autopsia anuales fueron calculadas y se analizaron las razones por las que no se hicieron autopsias. RESULTADOS: La tasa de autopsia promedio de mortinatos (MN) fue 59.6% (rango 51.9-76.7%), mientras que la tasa de autopsia promedio de las muertes neonatales tempranas (MNT) fue 47.9% (rango 34.4-63.2), con una tasa promedio general de autopsia perinatal de 54.0% (rango 42.2-62.2). Se requirieron autopsias en 79.3% y 51.7% de los MN y las MNT respectivamente. De las autopsias requeridas, se realizaron 81.7% (75.2% mortinatos; 92.5% MNT). En relación con las MNT, la no solicitud de autopsia se notó predominantemente en infantes prematuros de peso < 1000 g (75.2% de aquéllos no solicitados). Con respecto a los mortinatos, se desconoce en gran medida las razones por las que no se hizo una solicitud, excepto el no haber obtenido permiso, lo cual explica sólo el 20.3% de los casos. CONCLUSIONES: La tasa de autopsia perinatal promedio anual en el Hospital Universitario de West Indies entre 2002 y 2008 fue 54.0%. Esta cifra se halla por debajo de la tasa internacionalmente recomendada de 75%. La no solicitud de una autopsia fue el factor más significativo que contribuyó a ello. Las razones para esto no están completamente claras y requieren estudio posterior.

In enterovirus 71 encephalitis with cardio-respiratory compromise, elevated interleukin 1ß, interleukin 1 receptor antagonist, and granulocyte colony-stimulating factor levels are markers of poor prognosis.

BACKGROUND: Enterovirus 71 (EV71) causes large outbreaks of hand, foot, and mouth disease (HFMD), with severe neurological complications and cardio-respiratory compromise, but the pathogenesis is poorly understood. METHODS: We measured levels of 30 chemokines and cytokines in serum and cerebrospinal fluid (CSF) samples from Malaysian children hospitalized with EV71 infection (n = 88), comprising uncomplicated HFMD (n = 47), meningitis (n = 8), acute flaccid paralysis (n = 1), encephalitis (n = 21), and encephalitis with cardiorespiratory compromise (n = 11). Four of the latter patients died. RESULTS: Both pro-inflammatory and anti-inflammatory mediator levels were elevated, with different patterns of mediator abundance in the CSF and vascular compartments. Serum concentrations of interleukin 1ß (IL-1ß), interleukin 1 receptor antagonist (IL-1Ra), and granulocyte colony-stimulating factor (G-CSF) were raised significantly in patients who developed cardio-respiratory compromise (P = .013, P = .004, and P < .001, respectively). Serum IL-1Ra and G-CSF levels were also significantly elevated in patients who died, with a serum G-CSF to interleukin 5 ratio of >100 at admission being the most accurate prognostic marker for death (P < .001; accuracy, 85.5%; sensitivity, 100%; specificity, 84.7%). CONCLUSIONS: Given that IL-1ß has a negative inotropic action on the heart, and that both its natural antagonist, IL-1Ra, and G-CSF are being assessed as treatments for acute cardiac impairment, the findings suggest we have identified functional markers of EV71-related cardiac dysfunction and potential treatment options.

Investigation of perfusion in osseous vessels in close vicinity to piezo-electric bone cutting.

Cutting bones by piezosurgery leads to failure of perfusion at the site of the osteotomy, the cause of which cannot be identified immediately. Among other things the formation of vascular thrombi by the transmission of oscillations from the piezoelectric unit to the bone may be responsible. We used three output levels of oscillation that were predefined by the system. The outer cortical bone of the calvaria of rats (n=24) was removed horizontally and the intraosseous vessels exposed at the surface of the osteotomy. The blood flow was then examined repeatedly using intravital fluorescence microscopy. To calculate the transmission of oscillations to the bone, the spatial oscillation frequency of each calvarium and the contact pressure during removal of bone in vitro (n=18) were also examined. After removal of the bone there was constant blood flow at all three levels of oscillation output. In no case did an individual vessel seem to be occluded. The excitation oscillation of the bone was established at 2000 Hz in all spatial directions, irrespective of the predefined oscillation output. The application of piezosurgery does not cause the formation of vascular thrombi in the bone. This probably results from the oscillation damping properties of bone.

The influence of pressure changes on endodontically treated teeth during simulated dives.

AIM: To measure and evaluate pressure changes in the pulp chambers of extracted teeth exposed to hyperbaric conditions during root canal treatment. METHODOLOGY: A pressure sensor was inserted and sealed into the pulp chambers of extracted human molars (n = 6). The teeth were subjected to simulated dives to 4.5 bar in a diving chamber. During the simulated ascents and descents, the pressure within the pulp chamber was measured, and the difference between the pressure inside the pulp chamber and the pressure in the diving chamber was calculated. Each tooth underwent two dives with an intact pulp chamber, with a calcium hydroxide dressing, after root canal filling, and after adhesive sealing of the pulp chamber floor with a composite. Differences were analyzed statistically (P < 0.05) using one-way analysis of variance (anova). RESULTS: There were no significant pressure differences in teeth with an intact pulp chamber and teeth with a calcium hydroxide dressing. After root filling, however, the increase in pressure inside the pulp chamber was significantly lower (P < 0.05) than that in the diving chamber. After adhesive sealing of the pulp chamber floor with a composite, the pressure inside the pulp chamber was significantly lower (P < 0.05) than the pressure in the diving chamber. CONCLUSIONS: In root canal treatment, canal orifices should be sealed with an adhesively bonded composite filling before a dive. The use of a calcium hydroxide dressing after root canal preparation does not disqualify patients from diving.

[Reconstruction of complex midfacial defects with individualized titanium implants]. / Rekonstruktion komplexer Mittelgesichtsdefekte durch individualisierte Titanimplantate.

BACKGROUND: Loss of hard and soft tissue structures of the midface due to resection or trauma is associated with substancial functional and aesthetic deficits. Besides reconstruction of bony contours for preservation of orbit position and facial symmetry, reconstruction often requires simultaneous transplantation of soft tissue flaps for separation of nasal and oral cavities and refilling of soft tissue volume deficits. PATIENTS AND METHODS: A well-established procedure of our institution will be demonstrated in 10 exemplary patients, in which titanium meshes are customized for individual defect situations using computer-assisted techniques in combination with soft tissue transfer if required. RESULTS: According to our experience, this procedure provides satisfactory results in functional as well as in aesthetic respects. Especially in patients with loss of bony structures of the orbit and preservation of orbital contents, this procedure forms optimal preconditions for prevention of enophthalmos and diplopia by preservation of the original orbital volume. CONCLUSION: Individualized titanium implants should be used more frequently in clinical routine for reconstruction of complex midfacial defects.

Patient-reported adverse drug reactions and drug-drug interactions: a cross-sectional study on Malaysian HIV/AIDS patients.

OBJECTIVE: This study aimed to explore the adverse drug reactions (ADRs) reported by patients and to identify drug-drug interactions (DDIs) among human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients. SUBJECTS AND METHODS: This cross-sectional study was conducted at the Medication Therapy Adherence Clinic, Hospital Sungai Buloh, an HIV/AIDS referral centre. The patients were randomly selected and were encouraged to describe ADRs caused specifically by any of the prescribed antiretroviral drugs (ARDs). Sociodemographic characteristics were recorded from the patients' medical records. In addition data on antiretroviral treatment (ART), DDIs and other conventional medication were also documented. RESULTS: A total of 325 randomly selected HIV/AIDS patients with a mean age of 22.94 years participated in the study. The most frequently prescribed ARDs were lamivudine (64.6%), zidovudine (40.6%) and efavirenz (42.5%). Commonly reported ADRs were fatigue (54.8%), allergic reactions (41.5%), weight loss (41.5%), dry mouth (35.1%) and memory loss (35.1%). Female (87.8%), non-complementary and alternative medicine (CAM) users (87.3%) and participants below 50 years old (81.1%) were identified as having a higher prevalence of ADRs compared to males (79.6%), CAM users (78.7%) and participants aged 50 years or more (77.5%). Patient age was found to be significantly associated (p = 0.048) with the ADRs. In addition, a total of 44 cases of DDIs belonging to category D were also found in this study. CONCLUSIONS: This study enabled us to identify the most common ADRs and DDIs associated with the use of ART. Safe and effective treatment depends on the healthcare providers' knowledge of the same.

Sandwich osteotomy for vertical and transversal augmentation of the posterior mandible.

The aim of this study is to describe the treatment outcome after alveolar ridge augmentation in the atrophic posterior mandible by segmental sandwich osteotomy combined with an interpositional autograft prior to placement of endosseous implants. Thirteen consecutive patients (five males, mean age 48 years, and eight females, mean age 61 years) were included in this study. The postoperative course was uneventful in six patients. Sensory disturbances in the mental nerve were found in five patients, all of them with hypoaesthesia. None of these patients complained of permanent sensory disturbances. Vertical gain ranged from 2.0 to 7.8mm (mean value 4.61mm). Horizontal gain ranged from 2.0 to 6.3 (mean value 3.42mm). A total of 41 implants were placed in 22 surgical sites, 12 weeks after bone reconstruction. In conclusion, segmental mandibular sandwich osteotomy is recommended to meet the dimensional requirements of preimplant bone augmentation in atrophic posterior mandible.

Automated identification of diabetes type-2 subjects with and without neuropathy using eigenvalues.

Diabetes is a disorder of metabolism and has been a leading healthcare burden throughout the world. The most typical form of diabetes is type-2 diabetes. It is commonly developed in adults of age 40 and older. The purpose of this study is to identify the plantar pressure distribution in normal subjects, diabetic type-2 subjects with neuropathy, and diabetic type-2 subjects without neuropathy. Foot scan images were obtained using the F-Scan (Tekscan USA) in-shoe measurement system. The eigenvalues were evaluated from principal-component analysis after performing continuous wavelets transformation (CWT). The eigenvalues of CWT in regions 5 and 7 had shown excellent p values of more than 95 per cent confidence level when subjected to an analysis-of-variance test. These parameters were then presented to an artificial neural network (ANN) and a Gaussian mixture model (GMM) for automatic classification. The results show that the ANN classifier performs better than the GMM and is able to identify the unknown class with a sensitivity of 100 per cent and a specificity of 72 per cent.

Comparison of different harvesting methods from the flat and long bones of rats.

Different harvesting methods have been developed for bony augmentation before implantation. The aim of the present study was to assess the viability of endochondral (femoral) and membranous (mandibular) bone cells harvested by different methods under standard conditions in an animal model, and to investigate the surface of the bone in the harvested area. Samples of mandibular and femoral bone were harvested using a drilling burr, a piezoelectrical device, or a Safescraper(®). Blocks of bone that had been harvested with cutting forceps were used as controls. The size of the samples was measured and they were examined by conventional microscopy and immunohistochemical analysis; osteoblast-like cells were also cultured. The surface of the harvested area was analysed with scanning and conventional microscopy. There was no significant difference between mandibular and femoral bone in the size of particles harvested, but bone chips were significantly smaller when a drilling device had been used in both harvesting areas. Viability of cells in these smaller particles was significantly less than among cells harvested with a piezoelectrical device or Safescraper(®). Scanning microscopy showed a smooth bony surface where a drilling burr or piezoelectrical device had been used, whereas small disruptions were observed after the Safescraper(®) had been used. Harvesting of particulate bone is feasible using a drilling burr, piezoelectrical device, or Safescraper(®) from mandibular and femoral bone. The piezoelectrical device and the Safescraper(®) gave comparable results concerning the viability of osteoblast-like cells, and so are preferred to a drilling burr.

Double-grating-structured light microscopy using plasmonic nanoparticle arrays.

Structured illumination increases the spatial bandwidth of optical microscopes. We demonstrate bandwidth extension using a physical grating placed close to the sample. This comprises an array of elongated nanoparticles, whose localized surface plasmon resonance is polarization dependent. By arranging the particle orientation to vary with position the grating can be moved by changing the input polarization. A projected optical grating provides an additional independent mechanism for bandwidth extension. Experimental results showing bandwidth improvement in one direction are presented, and the measures necessary to extend the technique for routine imaging are discussed.

Motexafin gadolinium combined with prompt whole brain radiotherapy prolongs time to neurologic progression in non-small-cell lung cancer patients with brain metastases: results of a phase III trial.

PURPOSE: To determine the efficacy of motexafin gadolinium (MGd) in combination with whole brain radiotherapy (WBRT) for the treatment of brain metastases from non-small-cell lung cancer. METHODS AND MATERIALS: In an international, randomized, Phase III study, patients with brain metastases from non-small-cell lung cancer were randomized to WBRT with or without MGd. The primary endpoint was the interval to neurologic progression, determined by a centralized Events Review Committee who was unaware of the treatment the patients had received. RESULTS: Of 554 patients, 275 were randomized to WBRT and 279 to WBRT+MGd. Treatment with MGd was well tolerated, and 92% of the intended doses were administered. The most common MGd-related Grade 3+ adverse events included liver function abnormalities (5.5%), asthenia (4.0%), and hypertension (4%). MGd improved the interval to neurologic progression compared with WBRT alone (15 vs. 10 months; p = 0.12, hazard ratio [HR] = 0.78) and the interval to neurocognitive progression (p = 0.057, HR = 0.78). The WBRT patients required more salvage brain surgery or radiosurgery than did the WBRT+MGd patients (54 vs. 25 salvage procedures, p < 0.001). A statistically significant interaction between the geographic region and MGd treatment effect (which was in the prespecified analysis plan) and between treatment delay and MGd treatment effect was found. In North American patients, where treatment was more prompt, a statistically significant prolongation of the interval to neurologic progression, from 8.8 months for WBRT to 24.2 months for WBRT+MGd (p = 0.004, HR = 0.53), and the interval to neurocognitive progression (p = 0.06, HR = 0.73) were observed. CONCLUSION: In the intent-to-treat analysis, MGd exhibited a favorable trend in neurologic outcomes. MGd significantly prolonged the interval to neurologic progression in non-small-cell lung cancer patients with brain metastases receiving prompt WBRT. The toxicity was acceptable.

Imaging of the cell surface interface using objective coupled widefield surface plasmon microscopy.

We report on the development and on the first use of the widefield surface plasmon (WSPR) microscope in the examination of the cell surface interface at submicron lateral resolutions. The microscope is Kohler illuminated and uses either a 1.45 numerical aperture (NA) oil immersion lens, or a 1.65 NA oil immersion lens to excite surface plasmons at the interface between a thin gold layer and a glass or sapphire cover slip. Like all surface plasmon microscope systems the WSPR has been proven in previous studies to also be capable of nanometric z-scale resolutions. In this study we used the system to image the interface between HaCaT cells and the gold layer. Imaging was performed in air using fixed samples and the 1.45 NA objective based system and also using live cells in culture media using the 1.65 NA based system. Imaging in air enabled the visualisation of high resolution and high-contrast submicron features identified by vinculin immunostaining as component of focal contacts and focal adhesions. In comparison, imaging in fluid enabled cell surface interfacial interactions to be tracked by time-lapse video WSPR microscopy. Our results indicate that the cell surface interface and thus cell signalling mechanisms may be readily interrogated in live cells without the use of labelling techniques.

Towards the large-scale synthesis of carbon nanotubes in fluidised beds.

Carbon nanotubes (CNTs) are a form of crystalline carbon with extraordinary properties, making them valuable in a broad range of applications. However, the lack of suitable large-scale manufacturing techniques, which we define as being of the order 10000 tonnes per annum, continues to inhibit their widespread use. Of the three established synthesis methods for CNTs: (i) chemical vapour deposition (CVD), (ii) laser ablation, and (iii) arc discharge, CVD techniques show the greatest promise for economically viable, large-scale synthesis. In particular, the fluidised bed CVD (FBCVD) technique, where the CVD reaction occurs within a fluidised bed of catalyst particles, has the potential to produce high quality CNTs, inexpensively, in large quantities. In this work we report on the development of a catalytic chemical vapour deposition process, using batch fluidised bed reactors, for the synthesis of straight and spiral carbon nanotubes at pilot scale (up to 1 kg/hr). We believe this to be the first report of the synthesis of spiral carbon nanotubes using fluidised bed CCVD. Iron, nickel and cobalt transition metal catalysts supported on non-porous alumina substrates were fluidised in a mixture of nitrogen, hydrogen and ethylene at temperatures between 550 and 800 degrees C for between 15 and 90 minutes. Nanotube yield was inferred from thermogravimetric analysis and the quality and size of the CNTs from transmission electron microscopy. Conflicting information in the literature about the influence of synthesis parameters on CNT properties suggests that further investigation is necessary to understand the synthesis process at a fundamental level, i.e., independent of reactor design and operation.

A decade of Japanese encephalitis surveillance in Sarawak, Malaysia: 1997-2006.

Japanese encephalitis virus (JEV) is an important encephalitis virus in Asia, but there are few data on Malaysia. A hospital-based surveillance system for Japanese encephalitis (JE) has been in operation in Sarawak, Malaysia, for the last 10 years. JEV is endemic in Sarawak, with cases occurring throughout the year and a seasonal peak in the last quarter (one-way anova, P < 0.0001). Ninety-two per cent of 133 cases were children aged 12 years or younger; the introduction of JE vaccination in July 2001 reduced the number of JE cases (84 in the four seasons prior to vs. 49 in the six seasons after, McNemar's test, P = 0.0001). After implementation of the programme, the mean age of infected children increased from 6.3 to 8.0 years (Student's t-test, P = 0.0037), suggesting the need for a catch-up programme.

Imaging performance of widefield solid immersion lens microscopy.

We investigate the performance of a widefield imaging system employing an aplanatic solid immersion lens. Off-axis imaging quality is examined theoretically at different radii and thicknesses of the aplanatic solid immersion lens. It is found that field curvature is the major aberration affecting the imaging quality. Aberrations are measured experimentally, and the results are in very good agreement with those obtained from simulations and demonstrate the situations where high quality images can be obtained with the aplanatic solid immersion lens.