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Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence.

CONTEXT: Neuropsychiatric symptoms of dementia are common and associated with poor outcomes for patients and caregivers. Although nonpharmacological interventions should be the first line of treatment, a wide variety of pharmacological agents are used in the management of neuropsychiatric symptoms; therefore, concise, current, evidence-based recommendations are needed. OBJECTIVE: To evaluate the efficacy of pharmacological agents used in the treatment of neuropsychiatric symptoms of dementia. EVIDENCE ACQUISITION: A systematic review of English-language articles published from 1966 to July 2004 using MEDLINE, the Cochrane Database of Systematic Reviews, and a manual search of bibliographies was conducted. Inclusion criteria were double-blind, placebo-controlled, randomized controlled trials (RCTs) or meta-analyses of any drug therapy for patients with dementia that included neuropsychiatric outcomes. Trials reporting only depression outcomes were excluded. Data on the inclusion criteria, patients, methods, results, and quality of each study were independently abstracted. Twenty-nine articles met inclusion criteria. EVIDENCE SYNTHESIS: For typical antipsychotics, 2 meta-analyses and 2 RCTs were included. Generally, no difference among specific agents was found, efficacy was small at best, and adverse effects were common. Six RCTs with atypical antipsychotics were included; results showed modest, statistically significant efficacy of olanzapine and risperidone, with minimal adverse effects at lower doses. Atypical antipsychotics are associated with an increased risk of stroke. There have been no RCTs designed to directly compare the efficacy of typical and atypical antipsychotics. Five trials of antidepressants were included; results showed no efficacy for treating neuropsychiatric symptoms other than depression, with the exception of 1 study of citalopram. For mood stabilizers, 3 RCTs investigating valproate showed no efficacy. Two small RCTs of carbamazepine had conflicting results. Two meta-analyses and 6 RCTs of cholinesterase inhibitors generally showed small, although statistically significant, efficacy. Two RCTs of memantine also had conflicting results for treatment of neuropsychiatric symptoms. CONCLUSIONS: Pharmacological therapies are not particularly effective for management of neuropsychiatric symptoms of dementia. Of the agents reviewed, the atypical antipsychotics risperidone and olanzapine currently have the best evidence for efficacy. However, the effects are modest and further complicated by an increased risk of stroke. Additional trials of cholinesterase inhibitors enrolling patients with high levels of neuropsychiatric symptoms may be warranted.

Algorithms↗

Cold and heat tolerance of drosophilid flies with reference to their latitudinal distributions.

The relation between thermal tolerance and latitudinal distribution was studied with 30 drosophilid species collected from the cool-temperate region (Sapporo), the warm-temperate region (Tokyo and Kyoto) and the subtropical region (Iriomote island) in Japan. In addition, intraspecific variation was examined for five species collected from two localities. The subtropical strains of Scaptodrosophila coracina, Drosophila bizonata and D. daruma were less tolerant to cold than their temperate strains. However, the difference of cold tolerance between these two geographic strains was much smaller than the difference between the species restricted to the subtropical region and those occurring in the temperate region. In D. auraria and D. suzukii, no difference was observed in thermal tolerance between their cool- and warm-temperate strains. Thus, geographic variation in thermal tolerance within species was low or negligible. Interspecific comparisons by phylogenetic independent contrasts revealed that species which had the northern boundaries of their distributions at higher latitudes were generally more tolerant to cold than those which had their boundaries at lower latitudes. However, the data for some species did not agree with this trend. The use of man-protected warm places for overwintering, competition or predation would also affect their distributions. It also appeared that species which had their southern boundaries at higher latitudes were generally more cold-tolerant. The acquisition of cold tolerance may lower a fly's capacity to compete, survive or reproduce in warmer climates. On the other hand, no relation was observed between heat tolerance and latitudinal distribution. Heat tolerance was higher in species inhabiting openlands or the forest canopy than in those inhabiting the forest understorey.

Adaptation, Physiological↗

Effect of exogenous heparin on anchorage-independent growth of fibroblasts induced by transforming cytokines.

Heparin at concentrations below 100 micrograms/ml stimulated anchorage-independent growth of NRK 49F (normal rat kidney fibroblasts, American type culture collection) rat fibroblasts at suboptimal cytokine concentrations but inhibited it at higher heparin concentrations regardless of the cytokine concentration. Heparin did not stimulate growth above that seen at optimal cytokine concentrations, suggesting that it alters the cellular response to the cytokines. These data suggest natural protein-glycosaminoglycan interactions play a role in modulating or mediating the actions of transforming cytokines and suggest they may play a role in acquisition of the transformed phenotype.

Agar↗

Biological basis of sex differences in the propensity to self-administer cocaine.

Women are at greater risk for cocaine addiction than are men, and female rats similarly show a greater propensity to self-administer cocaine than do male rats. This could be due to the intrinsic sex differences in brain organization, to the activational effects of circulating gonadal hormones, or both. For example, estradiol enhances dopamine release in the striatum and nucleus accumbens, and facilitates the behavioral sensitization induced by repeated cocaine exposure. We report here that independent of circulating gonadal hormones, female rats acquire cocaine self-administration behavior more rapidly, and they self-administer more cocaine at a faster rate than do male rats. This indicates that there is an intrinsic difference between male and female subjects in the neural systems mediating drug-seeking behavior due to sexual differentiation of the brain. Furthermore, we find that the administration of estradiol to gonadectomized female subjects greatly facilitates the acquisition of cocaine self-administration. These data demonstrate that both intrinsic sex differences in brain organization and the actions of circulating estradiol contribute to increased vulnerability for cocaine use in female subjects.

Analysis of Variance↗

A Leishmania amazonensis ZIP family iron transporter is essential for parasite replication within macrophage phagolysosomes.

Infection of mammalian hosts with Leishmania amazonensis depends on the remarkable ability of these parasites to replicate within macrophage phagolysosomes. A critical adaptation for survival in this harsh environment is an efficient mechanism for gaining access to iron. In this study, we identify and characterize LIT1, a novel L. amazonensis membrane protein with extensive similarity to IRT1, a ZIP family ferrous iron transporter from Arabidopsis thaliana. The ability of LIT1 to promote iron transport was demonstrated after expression in yeast and in L. amazonensis LIT1-null amastigotes. Endogenous LIT1 was only detectable in amastigotes replicating intracellularly, and its intracellular expression was accelerated under conditions predicted to result in iron deprivation. Although L. amazonensis lacking LIT1 grew normally in axenic culture and had no defects differentiating into infective forms, replication within macrophages was abolished. Consistent with an essential role for LIT1 in intracellular growth as amastigotes, Deltalit1 parasites were avirulent. After inoculation into highly susceptible mice, no lesions were detected, even after extensive periods of time. Despite the absence of pathology, viable Deltalit1 parasites were recovered from the original sites of inoculation, indicating that L. amazonensis can persist in vivo independently of the ability to grow in macrophages. Our findings highlight the essential role played by intracellular iron acquisition in Leishmania virulence and identify this pathway as a promising target for therapeutic intervention.

Amino Acid Sequence↗

Colonization and cross-colonization of nursing home patients with trimethoprim-resistant gram-negative bacilli.

A prospective study of 67 patients in a nursing home and a subpopulation of 31 patients who were stratified according to functional level--a general measure of the amount of nursing care required by the patients--was performed. The goals of this study were (1) to determine whether antibiotic selection of resistant variants from within endogenous flora of hosts or horizontal transmission is more important in the development of colonization with trimethoprim-resistant gram-negative bacilli (TRGNB) in a nursing home; (2) to identify the mode(s) of transmission if horizontal transmission is more important; and (3) to identify risk factors for colonization and cross-colonization with TRGNB. Although a number of variables were associated with colonization, only a decreased functional level appeared to be independently associated with colonization. Isolates from the subpopulation were subtyped by restriction endonuclease digestion of cellular DNA, as were isolates from personnel of the nursing home. Results revealed that 16 of 21 staff members had 48 positive cultures for TRGNB. Of 25 typeable isolates, 12 from seven of the 21 staff members were identical to patient strains. Analysis of acquisition of new strains of TRGNB by members of the subpopulation showed that 67.5% were the result of cross-colonization. Our data are consistent with, but do not prove, the hypothesis that nurses' hands are the primary mode of transmission of TRGNB in this nursing home and suggest that most colonization could be prevented by interdicting horizontal transmission.

DNA, Bacterial↗

Gastric activity on dipyridamole 201Tl myocardial perfusion imaging: a clinically useful finding.

To determine the potential association of increased 201Tl uptake by the stomach with symptoms referable to gastritis, 39 consecutive patients experiencing chest pain syndromes underwent a routine dipyridamole 201Tl pharmacological stress test. With the patient in a fasting state, dipyridamole was infused intravenously (0.56 mg kg-1), shortly followed by 201Tl infusion and subsequent image acquisition for single photon emission tomography (SPET). The original 32 SPET images over 180 degrees of arc were interpreted without knowledge of clinical data, using a 4-point scoring system. Patients with active symptoms of gastro-oesophageal discomfort (n = 17) were found to have significantly greater 201Tl stomach uptake scores, compared to the little or no uptake in the 22 patients without such active symptoms (P = 0.0001). A stepwise logistic regression analysis was used to determine which factor(s) showed independent predictive value of 201Tl gastric uptake. The only two independent variables identified were the presence of active gastritis symptoms and the use of anti-gastritis medications. Elevated gastric 201Tl uptake may be a clinically useful finding indicative of gastric inflammation that may be of value in the differential diagnosis of chest and epigastric discomfort.

Aged↗

Diffusion-weighted imaging with navigated interleaved echo-planar imaging and a conventional gradient system.

PURPOSE: To demonstrate the technical feasibility and precision of a navigated diffusion-weighted (DW) MR imaging method with interleaved echo-planar imaging and test its diagnostic sensitivity for detection of ischemic stroke. MATERIALS AND METHODS: Apparent diffusion coefficient (ADC) measurements were performed in phantoms, and six healthy adult volunteers were examined to determine intrasubject (precision) and intersubject (reference range) variations in absolute ADC and relative ADC (rADC) measurements. DW imaging maps and lesion rADC values were also obtained in 34 consecutive stroke patients to evaluate the sensitivity and reliability of DW-interleaved echo-planar imaging for detection of ischemic brain damage. RESULTS: Phantom and volunteer ADC values were in excellent agreement with published data. The intrasubject variation of rADC was 6.2%. The ADC precision ranged from 6.5% in the subcortical white matter in the frontal lobe to 12.9% in the head of the caudate nucleus. Interleaved echo-planar imaging enabled rapid acquisition of high-quality images of the entire brain without substantial artifacts. Within the 1st week, the sensitivity of DW-interleaved echo-planar imaging for detection of acute infarction was 90% (18 of 20 true-positive studies) and independent of lesion location. CONCLUSION: DW-interleaved echo-planar imaging with phase navigation and cardiac triggering is robust, reliable, and fast. With high sensitivity for detection of early ischemic infarction, it is useful for examining stroke patients by using MR systems with conventional gradient hardware.

Adult↗

Effect of body size, ponderosity, and blood pressure on left ventricular growth in children and young adults in the Bogalusa Heart Study.

BACKGROUND: The measurement of left ventricular mass (LVM) is important because individuals with increased LVM are at increased risk for cardiovascular diseases, including myocardial infarction and congestive heart failure. There are limited longitudinal data on the acquisition of LVM in children and young adults and the relative importance of sex, growth, excess body weight, and blood pressure (BP) on change in LVM. METHODS AND RESULTS: The study cohort consisted of a cross section of 160 healthy children and young adults 9 to 22 years of age at first exam in the biracial community of Bogalusa, La. All had stable BP levels recorded over a 2- to 3-year period. Repeated examinations were performed 4 to 5 years apart. At each exam, 6 BPs were obtained with a mercury sphygmomanometer by trained examiners. The mean of the observations was used, with the fourth Korotkoff phase serving as the measure of diastolic BP. Anthropometric data, including height (HT), weight (WT), and triceps skin fold thickness (TSF), were also obtained, and M-mode echocardiograms were performed. Ponderal index (PI = WT/HT3) was used as a measure of weight-for-height. Tracking of HT (r = .68 to .76), WT (r = .73 to .82), PI (r = .77 to .89), TSF (r = .70 to .80), BP (r = .47 to .60), and LVM (r = .40 to .70) was strong in both sexes (P < .0001). LVM indexed for linear growth (LVM/HT2.7) tracked in females (r = .56, P < .0001) but not in males. In univariate cross-sectional analyses, LVM/HT2.7 correlated with WT, PI, and TSF in both sexes (r = .21 to .60, P < .05) and with systolic BP (SBP) in females (r = .23, P < .05). WT was the only independent correlate of LVM/HT2.7 in both sexes in multivariate cross-sectional analysis in a model containing age, SBP, WT, and TSF as independent variables (r2 = .08 to .28, P < .02). In longitudinal univariate analyses, initial measurements of WT, PI, and TSF predicted final LVM/HT2.7 in both sexes (r = .28 to .56, P < .01), and SBP was significant for females (r = .27, P < .05). In multivariate analyses, initial WT was associated with final LVM and LVM/HT2.7 in both sexes (r2 = .27 to .54, P < .01). Finally, baseline LVM correlated with final SBP in both sexes (r = .21 to .27, P < .05), and initial LVM/HT2.7 correlated with final SBP in females (r = .26, P < .05) with a trend for males (r = .17). CONCLUSIONS: These data indicate that linear growth is the major determinant of cardiac growth in children and that excess weight may lead to the acquisition of LVM beyond that expected from normal growth. Increased mass may also precede the development of increased BP. The development of obesity may therefore be a significant, and possibly modifiable, risk factor for developing left ventricular hypertrophy and hypertension, risk factors for cardiovascular morbidity and mortality.

Adolescent↗

A microscale electrospray interface for on-line, capillary liquid chromatography/tandem mass spectrometry of complex peptide mixtures.

A microcapillary liquid chromatography (HPLC) system designed for the gradient elution of peptide and protein samples at flow rates < 1 microL/min has been coupled to a triple-sector quadrupole mass spectrometer via a simple sheathless electrospray interface (microspray). The microspray interface used a flame-drawn, uncoated, fused silica needle with tip outer diameters in the range of 15-20 microm and an opening less than 5 microm in diameter. Online sample filtration to prevent clogging of the drawn needle was accomplished by using a hydrophilic PVDF membrane filter integrated into the needle assembly. The spray potential (0.5-1 kV) was applied directly to the sample stream through the capillary union. Stable electrospray conditions were obtained over the full range of the gradient (0-90% acetonitrile in water) and was generally independent of flow rate. Both off-line and online analyses of proteins and peptide digest mixtures were performed at sample levels less than 10 fmol. HPLC parameters could be optimized for either rapid LC/MS analysis or enhanced performance in LC/MS/MS experiments by modulation of the eluting peak widths. Additionally, flow could be greatly reduced as selected components pass through the interface to prolong the time available to collect mass spectral data. The reduced spectral background and peak width manipulation facilitated the acquisition of peptide production spectra (MS/MS) using real-time, automated instrument control procedures.

Chromatography, High Pressure Liquid↗

Collision-induced dissociative chemical cross-linking reagents and methodology: Applications to protein structural characterization using tandem mass spectrometry analysis.

Chemical cross-linking combined with mass spectrometry is a viable approach to study the low-resolution structure of protein and protein complexes. However, unambiguous identification of the residues involved in a cross-link remains analytically challenging. To enable a more effective analysis across various MS platforms, we have developed a novel set of collision-induced dissociative cross-linking reagents and methodology for chemical cross-linking experiments using tandem mass spectrometry (CID-CXL-MS/MS). These reagents incorporate a single gas-phase cleavable bond within their linker region that can be selectively fragmented within the in-source region of the mass spectrometer, enabling independent MS/MS analysis for each peptide. Initial design concepts were characterized using a synthesized cross-linked peptide complex. Following verification and subsequent optimization of cross-linked peptide complex dissociation, our reagents were applied to homodimeric glutathione S-transferase and monomeric bovine serum albumin. Cross-linked residues identified by our CID-CXL-MS/MS method were in agreement with published crystal structures and previous cross-linking studies using conventional approaches. Common LC/MS/MS acquisition approaches such as data-dependent acquisition experiments using ion trap mass spectrometers and product ion spectral analysis using SEQUEST were shown to be compatible with our CID-CXL-MS/MS reagents, obviating the requirement for high resolution and high mass accuracy measurements to identify both intra- and interpeptide cross-links.

Amino Acid Sequence↗

Evaluation of imaging performance of a taper optics CCD; FReLoN' camera designed for medical imaging.

The purpose of this work was to assess the imaging performance of an indirect conversion detector (taper optics CCD; FReLoN' camera) in terms of the modulation transfer function (MTF), normalized noise power spectrum (NNPS) and detective quantum efficiency (DQE). Measurements were made with a synchrotron radiation laminar beam at various monochromatic energies in the 20-51.5 keV range for a gadolinium-based fluorescent screen varying in thickness; data acquisition and analysis were made by adapting to this beam geometry protocols used for conventional cone beams. The pre-sampled MTFs of the systems were measured using an edge method. The NNPS of the systems were determined for a range of exposure levels by two-dimensional Fourier analysis of uniformly exposed radiographs. The DQEs were assessed from the measured MTF, NNPS, exposure and incoming number of photons. The MTF, for a given screen, was found to be almost energy independent and, for a given energy, higher for the thinnest screen. At 33 keV and for the 40 (100) microm screen, at 10% the MTF is 9.2 (8.6) line-pairs mm(-1). The NNPS was found to be different in the two analyzed directions in relation to frequency. Highest DQE values were found for the combination 100 microm and 25 keV (0.5); it was still equal to 0.4 at 51.5 keV (above the gadolinium K-edge). The DQE is limited by the phosphor screen conversion yield and by the CCD efficiency. At the end of the manuscript the results of the FReLoN characterization and those from a selected number of detectors presented in the literature are compared.

Diagnostic Imaging↗

Independent acquisition and insertion into different chromosomal locations of the same pathogenicity island in Yersinia pestis and Yersinia pseudotuberculosis.

We show that Yersinia pestis and pesticin-sensitive isolates of Y. pseudotuberculosis possess a common 34 kbp DNA region that has all the hallmarks of a pathogenicity island and is inserted into different asparaginyl tRNA genes at different chromosomal locations in each species. This pathogenicity island (YP-HPI) is marked by IS100, has a G + C content different from its host, is flanked by 24 bp direct repeats, encodes a putative, P4-like integrase and contains the iron uptake virulence genes from the pgm locus of Y. pestis. These findings indicate independent horizontal acquisition of this island by Y. pestis and Y. pseudotuberculosis. The two YP-HPI locations and their possession of an integrase gene support a model of site-specific integration of the YP-HPI into these bacteria.

Aspartate-tRNA Ligase↗

Free breathing 3D balanced FFE coronary magnetic resonance angiography with prolonged cardiac acquisition windows and intra-RR motion correction.

A shortcoming of today's coronary magnetic resonance angiography (MRA) is its low total scan efficiency (<5%), as only small well-defined fractions of the respiratory (50%) and cardiac (10%) cycle are used for data acquisition. These precautions are necessary to prevent blurring and artifacts related to respiratory and cardiac motion. Hence, scan times range from 4 to 9 min, which may not be tolerated by patients. To overcome this drawback, an ECG-triggered, navigator-gated free breathing radial 3D balanced FFE sequence with intra-RR motion correction is investigated in this study. Scan efficiency is increased by using a long cardiac acquisition window during the RR interval. This allows the acquisition of a number of independent k-space segments during each cardiac cycle. The intersegment motion is corrected using a self-guided epicardial fat tracking procedure in a postprocessing step. Finally, combining the motion-corrected segments forms a high-resolution image. Experiments on healthy volunteers are presented to show the basic feasibility of this approach.

Artifacts↗

Development and validation of a home-based, mirrored, gynecologic laparoscopy trainer.

STUDY OBJECTIVE: To develop and evaluate the usefulness of a home-based laparoscopy practice tool in terms of skills acquisition and practice pattern. DESIGN: Six mirrored laparoscopy trainers were designed and built. Participants were enrolled in a prospective randomized controlled trial and performed a series of skills with a video-endoscopic training tower and laparoscopic training box in timed pre- and post-tests over 5 weeks. Control and experimental cohorts practiced skills tests in different settings with different equipment. Data analysis used the t test and Wilcoxon rank-sum test. Analysis of variance/analysis of covariance models were used for independent variables. (Canadian Task Force classification I.) SETTING: Midwestern tertiary care teaching hospital. PARTICIPANTS: Third-year medical students rotating through their obstetrics and gynecology clerkship. INTERVENTIONS: Control cohort participants (n = 13) practiced the skills in the video-endoscopic laboratory while the experimental cohort (n = 13) received mirrored training boxes and practiced at home. MEASUREMENTS AND MAIN RESULTS: Both groups demonstrated significant improvement, with a trend favoring the control group (p = .08). Randomization group and number of practice sessions were significant variables favoring the control group and experimental group, respectively. CONCLUSION: Home-based practice on a mirrored laparoscopy trainer improves hand-eye coordination in inexperienced surgeons and results in more frequent practice.

Adult↗

Prevalence of unruptured intracranial aneurysms according to comorbidities, risk factors, country, and time period: a systematic review and meta-analysis.

BACKGROUND: The incidence of aneurysmal subarachnoid haemorrhage declined between 1980 and 2010, which coincided with a decline in smoking and prevalence of hypertension. We aimed to investigate whether the decrease in subarachnoid haemorrhage incidence is paralleled by declines in unruptured intracranial aneurysm (UIA) prevalence. METHODS: For this systematic review and meta-analysis, we searched Embase, PubMed, and Web of Science for articles published in any language from Jan 1, 2011 to Dec 31, 2025, and reassessed 68 articles published before March 1, 2011 from a 2011 systematic review and meta-analysis. Articles were eligible for inclusion if they used a cross-sectional or case-control design and provided the crude number of participants and those with UIA. We only included studies reporting numbers of UIA separately from ruptured aneurysms and with ten or more patients. Summary data were independently extracted by JD with AZ or CB and conflicts were resolved by GJER. The primary outcome was proportion of participants with UIA. Relative to a hypothetical reference population (mean age 50 years, 50% women, and no comorbidities), age and/or sex-adjusted prevalence ratios (PRs) for regions, comorbidities, and risk ratios (RRs) for female sex, smoking, and hypertension were estimated using generalised linear mixed models. A time trend analysis was done by binomial meta regression using the mid-year of data acquisition. We assessed the certainty of evidence using GRADE. The study was registered with PROSPERO, number CRD420261296728. FINDINGS: Our search screened 4708 studies. 67 reassessed and 95 newly identified articles, reporting on 316&#x2008;131 participants and 11&#x2008;822 people with UIAs, were included in our meta-analysis. In the reference population, the estimated prevalence of UIAs was 3&#xb7;9% (95% CI 3&#xb7;0-5&#xb7;1). The prevalence of UIAs in individuals with atherosclerosis was 5&#xb7;5% (4&#xb7;7-6&#xb7;4; 2229 of 40970 participants) and the adjusted PR was 1&#xb7;3 (95% CI 0&#xb7;8-2&#xb7;0) compared with the reference population. For positive family history of aneurysmal subarachnoid haemorrhage (aSAH) or UIA, the UIA prevalence was 7&#xb7;9% (5&#xb7;6-11&#xb7;1; 412 of 4252 participants) and the adjusted PR was 2&#xb7;4 (0&#xb7;5-11&#xb7;2). For connective-tissue disorder, the UIA prevalence was 10&#xb7;3% (6&#xb7;5-16&#xb7;0; 94 of 879 participants) and the adjusted PR was 3&#xb7;9 (2&#xb7;0-7&#xb7;6). For autosomal dominant polycystic kidney disease (ADPKD), the UIA prevalence was 12&#xb7;8% (9&#xb7;2-17&#xb7;6; 293 of 1990 participants) and the adjusted PR was 4&#xb7;4 (1&#xb7;5-12&#xb7;6). RRs were for current smoking 1&#xb7;4 (1&#xb7;2-1&#xb7;6; 798 of 27911 participants), for having hypertension 1&#xb7;6 (1&#xb7;5-1&#xb7;7, 4043 of 83053 participants), and for female sex 1&#xb7;9 (1&#xb7;8-2&#xb7;0; 3415 of 65020 women and 2122 of 76130 men). In studies on healthy individuals with MR angiography or CT angiography as imaging modality, the prevalence in 2016-2022 was 6&#xb7;6% (6&#xb7;3-6&#xb7;8; 2904 of 41191 participants). The adjusted PR was 1&#xb7;8 (1&#xb7;1-2&#xb7;8) for 2016-2022 versus 2002-2015. Prevalence of UIAs of 5 mm or larger was 0&#xb7;7% (0&#xb7;6-0&#xb7;8) in 2002-2015 and 1&#xb7;4% (1&#xb7;0-1&#xb7;9) in 2016-2022. The UIA prevalence did not differ between countries. &#x3c4;2 showed significant heterogeneity between studies. The certainty of the evidence ranged from very low to moderate. INTERPRETATION: Prevalence of UIA is increasing, particularly over the past two decades. This increase is only in part explained by improved detection of small UIAs and an ageing population, and other factors-such as environmental-are likely involved. Alongside patients with ADPKD and a positive family history of aSAH, patients with connective-tissue disorders had a higher prevalence of UIA than the reference population. Our findings warrant further investigation into the potential benefit of personalised screening and management strategies in groups at high risk for having UIAs. FUNDING: None.

Humans↗

New developments in planar array infrared spectroscopy.

A planar array infrared (PA-IR) spectrograph offers several advantages over other infrared approaches, including high acquisition rate and sensitivity. However, it suffers from some important drawbacks, such as a limited spectral range and a significant curvature of the recorded spectral images, which still need to be addressed. In this article, we present new developments in PA-IR spectroscopy that overcome these drawbacks. First, a data processing method for the correction of the curvature observed in the spectral images has been developed and refined. In addition, a dual-beam instrument that allows the simultaneous recording of two independent spectral images has been developed. These two improvements have been combined to demonstrate the real-time background correction capability of PA-IR instruments. Finally, the accessible spectral range of the PA-IR spectrograph has been extended to cover simultaneously the methylene stretching (3200-2800 cm(-1)) and the finger-print (2000-1000 cm(-1)) spectral regions.

Algorithms↗

A 24-m3 direct heat-sink calorimeter with on-line data acquisition, processing, and control.

The construction and performance of a 24-m3 direct heat-sink calorimeter for continuous measurement of evaporative and sensible heat loss in human subjects are described. Extensive use of real-time processing for compensation of physical time constants and delays made it possible to solve response-time and stability problems associated with the large volume. The performance characteristics of the calorimeter are 1) a linear response between 0 and 320 W (471 g . h-1) for evaporative heat with a precision of 4.0-0.6% in the range 25-100 W, 2) a linear response between 0 and 280 W for sensible heat with a precision of 1.4-0.2% in the range 50-200 W, 3) a stability corresponding to a drift of less than 0.6 W (24 and 72 h) on both evaporative and sensible heat outputs and 24- and 72-h standard deviations (values every 2 min) of 0.3 and 0.4 W for evaporative heat and 0.6 and 0.7 W for sensible heat, 4) response times (95%) of 15 min for both evaporative and sensible heat, 5) independency on the position of the calibration source within the chamber, 6) no measurable "cross talk" between evaporative and sensible heat inputs, 7) negligible dependency of the external air humidity between 14 and 70%, and 8) operating temperature range from 18 to 30 degrees C. More than 40 experiments of 25-h duration with human subjects have been carried out. In no case was any discomfort recorded. An example of the 25-h continuous evaporative and sensible heat output tracing of one experiment is given.

Body Temperature↗