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A chromium terephthalate-based solid with unusually large pore volumes and surface area.

We combined targeted chemistry and computational design to create a crystal structure for porous chromium terephthalate, MIL-101, with very large pore sizes and surface area. Its zeotype cubic structure has a giant cell volume (approximately 702,000 cubic angstroms), a hierarchy of extra-large pore sizes (approximately 30 to 34 angstroms), and a Langmuir surface area for N2 of approximately 5900 +/- 300 square meters per gram. Beside the usual properties of porous compounds, this solid has potential as a nanomold for monodisperse nanomaterials, as illustrated here by the incorporation of Keggin polyanions within the cages.

Journal Article↗

A novel fluorescent protein-based biosensor for gram-negative bacteria.

Site-directed mutagenesis of enhanced green fluorescent protein (EGFP) based on rational computational design was performed to create a fluorescence-based biosensor for endotoxin and gram-negative bacteria. EGFP mutants (EGFP(i)) bearing one (G10) or two (G12) strands of endotoxin binding motifs were constructed and expressed in an Escherichia coli host. The EGFP(i) proteins were purified and tested for their efficacy as a novel fluorescent biosensor. After efficient removal of lipopolysaccharide from the E. coli lysates, the binding affinities of the EGFP(i) G10 and G12 to lipid A were established. The K(D) values of 7.16 x 10(-7) M for G10 and 8.15 x 10(-8) M for G12 were achieved. With high affinity being maintained over a wide range of pH and ionic strength, the binding of lipid A/lipopolysaccharide to the EGFP(i) biosensors could be measured as a concentration-dependent fluorescence quenching of the EGFP mutants. The EGFP(i) specifically tagged gram-negative bacteria like E. coli and Pseudomonas aeruginosa, as well as other gram-negative bacteria in contaminated water sampled from the environment. This dual function of the EGFP(i) in detecting both free endotoxin and live gram-negative bacteria forms the basis of the development of a novel fluorescent biosensor.

Biosensing Techniques↗

Incremental nature of anterior eye grading scales determined by objective image analysis.

AIM: To use previously validated image analysis techniques to determine the incremental nature of printed subjective anterior eye grading scales. METHODS: A purpose designed computer program was written to detect edges using a 3 x 3 kernal and to extract colour planes in the selected area of an image. Annunziato and Efron pictorial, and CCLRU and Vistakon-Synoptik photographic grades of bulbar hyperaemia, palpebral hyperaemia roughness, and corneal staining were analysed. RESULTS: The increments of the grading scales were best described by a quadratic rather than a linear function. Edge detection and colour extraction image analysis for bulbar hyperaemia (r2 = 0.35-0.99), palpebral hyperaemia (r2 = 0.71-0.99), palpebral roughness (r2 = 0.30-0.94), and corneal staining (r2 = 0.57-0.99) correlated well with scale grades, although the increments varied in magnitude and direction between different scales. Repeated image analysis measures had a 95% confidence interval of between 0.02 (colour extraction) and 0.10 (edge detection) scale units (on a 0-4 scale). CONCLUSION: The printed grading scales were more sensitive for grading features of low severity, but grades were not comparable between grading scales. Palpebral hyperaemia and staining grading is complicated by the variable presentations possible. Image analysis techniques are 6-35 times more repeatable than subjective grading, with a sensitivity of 1.2-2.8% of the scale.

Analysis of Variance↗

Physiotherapy exercises and back pain: a blinded review.

OBJECTIVE: To determine the quality of randomised controlled trials of exercise therapy for back pain. DESIGN: Computer aided search of published papers and blinded assessment of the methods of studies. SUBJECTS: 23 randomised controlled trials, of which 16 studied exercise therapy given by physiotherapists to individual patients with back pain. Other conservative treatments could be included. MAIN OUTCOME MEASURES: Score for quality of methods (based on four main categories: study population, interventions, measurement of effect, and data presentation and analysis) and main conclusion of author(s) with regard to exercise therapy. RESULTS: Only four studies scored more than 50 points (maximum 100), indicating that most were of poor quality. Six studies found that exercise was better than reference treatments and 10 reported it to be no better or worse than the reference treatment. Those reporting positive results tended to have higher methods scores (4/6 positive v 4/10 negative scored greater than or equal to 42). CONCLUSIONS: No conclusion can be drawn about whether exercise therapy is better than other conservative treatments for back pain or whether a specific type of exercise is more effective. Further trials are needed in which greater attention is paid to methods of study.

Back Pain↗

Spinal manipulation and mobilisation for back and neck pain: a blinded review.

OBJECTIVE: To assess the efficacy of spinal manipulation for patients with back or neck pain. DESIGN: Computer aided search for published papers and blinded assessment of the methods of the studies. SUBJECTS: 35 randomised clinical trials comparing spinal manipulation with other treatments. MAIN OUTCOME MEASURES: Score for quality of methods (based on four main categories: study population, interventions, measurement of effect, and data presentation and analysis) and main conclusion of author(s) with regard to spinal manipulation. RESULTS: No trial scored 60 or more points (maximum score 100) suggesting that most were of poor quality. Eighteen studies (51%) showed favourable results for manipulation. In addition, five studies (14%) reported positive results in one or more subgroups. Of the four studies with 50-60 points, one reported that manipulation was better, two reported that manipulation was better in only a subgroup, and one reported that manipulation was no better or worse than reference treatment. Eight trials attempted to compare manipulation with some placebo, with inconsistent results. CONCLUSIONS: Although some results are promising, the efficacy of manipulation has not been convincingly shown. Further trials are needed, but much more attention should be paid to the methods of study.

Acute Disease↗

Choosing the preventive workload in general practice: practical application of the Coronary Prevention Group guidelines and Dundee coronary risk-disk.

OBJECTIVE: To determine the workload implications for general practice of the Coronary Prevention Group and British Heart Foundation action plan for preventing heart disease. DESIGN: Computer simulation of plan, including calculation of Dundee risk scores, with data from OXCHECK trial. SUBJECTS: 4759 patients aged 35-64 who had health checks during 1989-91. MAIN OUTCOME MEASURE: Effect of using different risk scores as thresholds on workload and coverage of patients at known risk. Thresholds of 6-20 were used for cholesterol screening (nearset) and 4-16 for special care (preset). RESULTS: On the basis of workload a nearset of 8 and preset of 12 would be reasonable. This implies cholesterol measurement in 1794 (37.7%) patients and special care in 1074 (22.6%). However, many patients with single risk factors were not allocated to special care at these thresholds: 11 (37.9%) patients with cholesterol concentrations > or = 10 mmol/l, 21 (33.9%) with systolic pressure > or = 180 mm Hg, and 213 (40.7%) heavy smokers (> 20 cigarettes/day) were missed. The distribution of scores was similar in those at established clinical risk, those with family history of heart disease, and others. CONCLUSION: The guidelines may help to make best use of resources within specific age-sex groups but sound protocols for unifactorial risk assessment and modification remain essential.

Adolescent↗

Definition of an immunogenic region within the ovarian tumor antigen stratum corneum chymotryptic enzyme.

PURPOSE: The serine protease stratum corneum chymotryptic enzyme (SCCE) is overexpressed by ovarian tumor cells, but is not expressed by normal tissues, suggesting that SCCE may be an attractive target for immunotherapy. In this study, we tested the hypothesis that dendritic cells loaded with SCCE peptides will induce ovarian tumor antigen-specific CD8+ CTL responses and antigen-specific CD4+ helper T cell responses. EXPERIMENTAL DESIGN: Computer algorithms were used to identify candidate HLA-A2.1-restricted CD8+ CTL epitopes and HLA-DR-binding CD4+ helper T cell epitopes within SCCE. CD8+ CTL stimulated with peptide-loaded dendritic cells were tested against targets expressing endogenous SCCE, including HLA-A2.1-matched ovarian tumor cells. Dendritic cells were also loaded with an extended SCCE peptide, SCCE 110-139, which encompassed a defined CD8+ CTL epitope and multiple candidate CD4+ T helper cell epitopes. RESULTS: CD8+ CTL specific for SCCE 123-131 lysed autologous macrophages infected with an SCCE-expressing recombinant adenovirus, and also lysed HLA-A2.1-matched, SCCE-expressing ovarian tumor cells. Dendritic cells loaded with SCCE 5-13 peptide stimulated an HLA-A2.1-restricted CD8+ CTL response, but with a reduced level of lysis against ovarian tumor cells. Dendritic cells loaded with SCCE 110-139 induced antigen-specific CD4+ T cell and CD8+ T cell responses. Although SCCE 110-139-loaded dendritic cells processed and presented the 123-131 epitope, the dominant CD8+ CTL response was directed against alternative epitopes within SCCE 110-139. CONCLUSIONS: The 110-139 region of SCCE incorporates multiple CD8+ CTL and CD4+ helper T cell epitopes, and represents an attractive target antigen for immunotherapy of ovarian cancer.

Amino Acid Sequence↗

Long-term changes in transperitoneal water transport during continuous ambulatory peritoneal dialysis.

9 patients were observed prospectively during 14-40 months 003 continuous ambulatory peritoneal dialysis (CAPD) treatment. From start of CAPD, each patient recorded dwell time, drained ultrafiltration volume (delta V), initial glucose concentration in dialysate, dialy fluid intake, body weight and blood pressure on a special form. These data, together with monthly values for albumin, urea, creatinin, phosphate, glucose and beta 2-microglobulin in plasma and in instilled dialysate, were later fed into a specially designed computer program to compare changes in the monthly mean (+/- SEM) values. During 5 episodes of peritonitis, daily changes in delta V were also computed. A long-term increase in delta V was found in 4 and a decrease in 5 patients. In all 9 patients delta V changed intermittently. All changes were most pronounced for long dwell times as compared to shorter dwell exchanges. The decrease in delta V started within the first 12 months of treatment. In the daily routine were aware of decreased ultrafiltration capacity in 3 patients only. Intermittent monthly changes in delta V could partly be correlated to changes in daily fluid intake. No correlations were found between long-term changes in delta V and fluid intake. All except 1 patient gained progressively in body weight, but without correlations to fluid balance, blood pressure and plasma albumin concentration. At the start of the observation period, most patients loosing delta V during this study appeared to have a more permeable membrane with a higher absorption rate of glucose and higher equilibration ratios for creatinine and beta 2-microglobulin in 5-hours drained dialysate as compared with the other patients. However, this was not statistically different between the two groups of patients. During the observation period, most patients with decreased delta V also increased transperitoneal solute transport, while the solute transport decreased in patients with increasing delta V, but these changes were only significant for some patients. During peritonitis, delta V decreased significantly 1 day before any other signs of peritonitis. All changes in delta V were most pronounced for long dwell times as compared with short dwell times. It is suggested that changes in ultrafiltration can be related to altered permeability of the peritoneal membrane, which appear earlier and more frequent than suggested by others, and any loss of delta V can be explained by a more permeable ('open') peritoneal membrane. It is also possible that different diseases act differently on the permeability of the peritoneal membrane.

Adult↗

Changing practice and costs of carotid endarterectomy in Toronto, Canada.

BACKGROUND AND PURPOSE: During our annual audits of carotid endarterectomy (CEA) in Toronto metropolitan hospitals, we have been aware of major changes in the practice of this operation in recent years. To evaluate the effect of changing practice on costs of carotid endarterectomy, we have therefore compared the effects of changes in length of stay, complication rates, and other variables on cost during the last 3 years for which we have complete data. METHODS: We evaluated 757 consecutive patients, of whom 600 had CEA procedures in 3 teaching hospitals, and 190 procedures in 2 community hospitals in metropolitan Toronto. We estimated costs using a specially designed computer program, Transitional System Incorporated, including surgical complications, in patients admitted between January 1994 and December 1996. RESULTS: There was a significant decrease in length of stay in both groups of hospitals, mainly due to preoperative outpatient evaluation but also due to lower complication rates, which probably reflect an increase in asymptomatic surgery in both hospital groups. Costs fell from approximately $8000 per procedure to $5000 in asymptomatic patients and from approximately $10,000 to $7000 in symptomatic patients (Can $). CONCLUSIONS: Major changes in the management of patients undergoing CEA have resulted in a significant decrease in both length of hospital stay and utilization of postoperative intensive care. At the same time, complication rates have significantly fallen, although our mortality and morbidity figures remain slightly higher than those from published multicenter trials. Future changes in surgical practice in Canada, including noninvasive carotid imaging, should produce even lower costs within the next few years.

Aged↗

Reducing the lateral force acting on the patella does not consistently decrease patellofemoral pressures.

BACKGROUND: Extensor mechanism procedures that decrease the lateral component of the patellar tendon or quadriceps force acting on the patella do not consistently reduce pain. HYPOTHESIS: Patellofemoral treatments do not consistently decrease patellofemoral pressures because of variations in the moments acting on the patella. STUDY DESIGN: Computer simulation study. METHODS: Computational models of 4 knees were constructed to characterize the patellofemoral pressure distribution during simulated squatting from 40 degrees to 90 degrees. The knees were given an initial Q angle of 25 degrees. Patellofemoral treatments were simulated by increasing the percentage of the quadriceps force applied by the vastus medialis by 50% and by medializing the tibial tuberosity to decrease the Q angle to 15 degrees. RESULTS: Decreasing the Q angle caused a larger decrease in the lateral component of the force applied by the quadriceps and patellar tendon than did increasing the force applied by the vastus medialis and, therefore, was more effective at decreasing patellofemoral pressures and the force needed to resist lateral subluxation. Both treatments also decreased the moments acting to rotate the distal patella laterally and tilt the patella laterally during flexion. Variations in these moments increased patellofemoral pressures for some knees. CONCLUSIONS: Treatments that reduce patellofemoral subluxation can have an unexpected influence on patellofemoral pressures because of the moments acting on the patella. CLINICAL RELEVANCE: Extensor mechanism procedures that restore patellofemoral stability may not provide pain relief.

Biomechanical Phenomena↗

First metatarsal bone: an anatomic study.

BACKGROUND: The purpose of this study was to establish the range of anatomic variations of the first metatarsal bone, including both the angulations of the articular surfaces and the dimensions of the bone in a large sample. METHODS: Four hundred and seventy-eight first metatarsal bones of 239 cadaver specimens were studied. The following parameters were recorded: the distal metatarsal articular angle (DMAA), distal metatarsal articular surface shape, proximal metatarsal articular angle (PMAA), the first metatarsal bone length and width at the mid-region of the shaft, and the existence of a joint between the bases of the first and second metatarsals. These parameters were correlated to the specimen's age, sex, race, height, and weight. The DMAA and PMAA were measured from a digital picture of the first metatarsal bone by a specially designed computer analysis program. RESULTS: Males and African-American race had a longer and wider metatarsal. The joint between the first and second bases was present in 25% of the population. The DMAA ranged from -14 degrees of medial deviation to 30 degrees of lateral deviation with an overall average of 8.21 degrees. The DMAA increased 1 to 3 degrees with every 10 years in age for both right and left bones with a p value of < 0.01 and < 0.001, respectively, and the average increase from 20 to 60 years of age was 4.5 degrees. The PMAA ranged from -13.8 degrees of lateral deviation to 12.7 degrees of medial deviation with an overall average of -1 degrees. PMAA significantly deviated laterally in the presence of a joint between the bases of the first and second metatarsals (p < 0.001). The male and female means for the DMAA and PMAA were nearly equal. CONCLUSIONS: The DMAA had a wider range than reported in the literature, and it increased with age. The first-second metatarsal joint was accompanied by lateral deviation of the PMAA. CLINICAL RELEVANCE: Laterally deviated PMAA could predispose to a varus deformity of the first metatarsal.

Adult↗

Measuring outcome in community-based rehabilitation services for people who have suffered traumatic brain injury: the Community Outcome Scale.

OBJECTIVE: To develop a way of measuring long-term outcomes after traumatic brain injury (TBI) that takes account of individual circumstances. DESIGN: Reports by head-injured people and their families about problems and coping strategies were elicited via semi-structured interviews. Specially designed computer software was used to record problems and strengths and to measure their impact for the individual on four handicap dimensions. SETTING: Interviews took place in the respondents' homes. SUBJECTS: Between 1992 and 1997 the services at 10 rehabilitation centres in England were evaluated. Subjects were men and women aged between 16 and 65 who had suffered TBI and who had been referred for treatment to one of the centres under study. INTERVENTIONS: Head-injured people and their families were interviewed three months, 18 months and in some cases 36 months after recruitment. MAIN OUTCOME MEASURES: The Hospital Anxiety and Depression Scale (HAD) and the Functional Independence/Assessment Measure (FIM/FAM) were used to validate relevant dimensions of the new scale. RESULTS: A measure of long-term outcome was developed and called the Community Outcome Scale. Relevant dimensions of the scale showed significant correlation with the HAD and with items of the FIM/FAM. CONCLUSION: The scale captures information which no other instrument does, and merits further validation.

Adolescent↗

Lung volume, gas mixing, and mechanics of breathing in mechanically ventilated very low birth weight infants with idiopathic respiratory distress syndrome.

We assessed pulmonary function in 14 mechanically ventilated newborn very low birth weight infants with idiopathic respiratory distress syndrome by means of a face-out, volume displacement body plethysmograph and nitrogen washout analyses. Specially designed computer programs were used for calculations of lung volumes, ventilation, gas mixing efficiency, and mechanical parameters. In addition to very low compliance and moderately elevated resistance of the respiratory system, there were considerably impaired gas mixing efficiency and low functional residual capacity (FRC). No correlations between positive end-expiratory pressure and mean airway pressure versus compliance, resistance, or FRC could be found. Neither could correlations be found between FRC and compliance or FRC and the calculated right to left shunt.

Female↗

Decreased basal and stimulated thyrotropin secretion in healthy elderly men.

To delineate the effects of aging on basal and stimulated TSH secretion, we studied the 24-h profile of plasma TSH levels and the TSH response to TRH stimulation (200 micrograms TRH, iv) in eight healthy elderly men, aged 67-84 yr, and eight normal young men, aged 20-27 yr. Subjects with thyroid antibodies against microsomal or thyroglobulin antigens were excluded. During the 24-h study, blood was sampled at 15-min intervals. TSH levels were measured by an ultrasensitive immunoradiometric assay. Sleep was polygraphically monitored, and circadian and pulsatile TSH variations were quantified using specifically designed computer algorithms. In older men, the 24-h mean TSH concentration was approximately 50% lower than that in young men (0.78 +/- 0.37 vs. 1.43 +/- 0.41 microU/mL; P less than 0.01), but basal T3 levels were only slightly lower (93 +/- 12 vs. 115 +/- 16 ng/dL; P less than 0.02), while basal T4 levels were normal. The normal diurnal variation of TSH levels, with a nocturnal acrophase and an afternoon nadir, as well as the pulsatile nature of TSH release were preserved in elderly men. When expressed in microunits per mL, the amplitude of these temporal variations was reduced in elderly men compared to that in younger subjects. However, when expressed in relation to the mean TSH levels, the amplitudes of diurnal and pulsatile variations were similar in both groups of subjects. TRH-induced TSH secretion was lower in old than in young men (area under the curve, 15.9 +/- 6.3 microU/mL.10 min in elderly men vs. 42.0 +/- 16.6 microU/mL.10 min in young men; P less than 0.002). However, the TRH-induced elevations of T3 and T4 were of similar magnitude in both groups. These results indicate that in healthy elderly men, the overall 24-h TSH secretion is decreased, and the pituitary is less responsive to stimulation by TRH. However, the chronobiological modulation is preserved. These alterations could reflect an adaptative mechanism to the reduced need for thyroid hormones in old age. The thyroid keeps an intact capacity to respond to acute increases in TSH concentrations.

Adult↗

Changing patterns of presentations of patients with HIV-related disease at a tertiary referral centre and its implications for physician training.

Highly active antiretroviral therapy (HAART) has been shown to be highly effective in controlling HIV-related disease progression. Our objective was to determine whether HAART had altered the spectrum of HIV-related disease presentations at a tertiary medical referral centre and if a change in the clinical presentations of HIV-infected individuals to the hospital had impacted on physicians' training. A retrospective study which examined all admissions of HIV-infected patients identified between 1 October 1996 to 30 September 1998 using a hospital-designed computer database was undertaken at the Beth Israel Deaconess Medical Center (BIDMC) tertiary medical referral centre. All medical residents were surveyed in order to assess their knowledge of HIV-associated admissions and their confidence treating HIV-infected patients. There were significant changes in the admitting diagnosis for HIV-related illness between 1996 and 1998. Admissions for opportunistic infections (OIs) declined whereas admissions with bacterial infections increased significantly. Use of HAART remained stable between the 2 years of the study. Physicians' overestimated the use of HAART and only 8% of residents felt very comfortable taking care of an HIV-infected patient. In conclusion, the spectrum of presentations with HIV-related disease to a tertiary referral centre continues to change in the HAART era and impacts on physicians' experience of the management of HIV disease.

AIDS-Related Opportunistic Infections↗

Uptake of 99mTc-MDP after uncemented hip arthroplasty: a quantitative analysis of findings around the femoral component in asymptomatic patients.

We studied the pattern of 99mTc-methylene diphosphonate uptake around uncemented femoral components in 44 asymptomatic hip arthroplasties, performing isotope scans at intervals from 4 to 48 months after operation. We used phase-II images obtained with a high-resolution gamma camera and measured the activity in various zones using a specially designed computer program. The components studied at 4, 6, 9 and 12 months were coated with hydroxyapatite (HA) and those studied at 18, 24, 36 and 48 months were not coated. We found a statistically significant fall in activity between four and six months around HA-coated prostheses in all five femoral periprosthetic zones. After six months activity was relatively uniform, but remained higher than that in normal femoral bone at 48 months in non-coated prostheses. We discuss the application of these patterns in the evaluation of painful cementless hip arthroplasties.

Adult↗

Phase calibration of spatially nonuniform spatial light modulators.

A new 512 x 512 pixel phase-only spatial light modulator (SLM) has been found to deviate from being flat by several wavelengths. Also, the retardation of the SLM relative to voltage varies across the device by as much as 0.25 wavelength. The birefringence of each pixel as a function of address voltage is measured from the intensity of the SLM between crossed polarizers. To these responses are added a reference spatial phase measured by phase shifting interferometry for a single address voltage. Fits to the measured data facilitate the compensation of the SLM to a root-mean-square wave-front error of 0.06 wavelength. The application of these corrections to flatten the full aperture of the SLM sharpens the focal plane spot and reduces the distortion of computer-designed diffraction patterns.

Journal Article↗

Design of diffractive optical elements for the fractional Fourier transform domain: phase-space approach.

Phase-space optics is used to relate the problem of designing diffractive optical elements for any first-order optical system to the corresponding design problem in the Fraunhofer diffraction regime. This, in particular, provides a novel approach for the fractional Fourier transform domain. For fractional Fourier transforms of arbitrary order, the diffractive element is determined as the optimum design computed for a generic Fourier transform system, scaled and modulated with a parabolic lens function. The phase-space description also identifies critical system parameters that limit the performance and applicability of this method. Numerical simulations of paraxial wave propagation are used to validate the method.

Journal Article↗