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PubMed2004

Long-term mobility monitoring of older adults using accelerometers in a clinical environment.

OBJECTIVE: To assess the accuracy of accelerometer-based mobility monitoring during extended measurements on older adults in a clinical setting and to evaluate two different approaches to thresholding. DESIGN: The monitoring device consisted of two Analog Devices ADXL202 accelerometers, an ambulatory data-logger and associated cabling. The monitoring system used custom-designed analysis software to detect activities of daily living, namely duration of sitting, standing, lying and moving during the period monitored. An investigator shadowed the subjects throughout the recording period. SUBJECTS AND SETTING: This study monitored five older adults, with varying degrees of mobility, resident in a rehabilitation clinic, over four days. INTERVENTIONS: The accelerometer data were analysed using a MATLAB program that allowed trunk and thigh threshold angles to be set to distinguish between sitting, standing, lying and moving. Two different approaches to setting these thresholds were investigated: (1) using a midpoint tolerance value of 45 degrees and (2) using a 'best estimate' tolerance value. The analysis program generates a summary of activities, which is then compared line-by-line with the manual summary created by the observer. The result was a hit/miss ratio representative of the system's accuracy. RESULTS: The detection accuracies for sitting and lying using a mid-point tolerance value were poor, with an average detection accuracy of 75% obtained. The 'best estimate' approach improved the detection accuracies for sitting and lying by approximately 18% to an average value of 93%. CONCLUSION: In a population of older adults, the static activities of sitting, standing and lying and dynamic activities can be distinguished using the technique and threshold values outlined here to a degree of accuracy of 92% and higher.

Activities of Daily Living↗

PubMed1994

On the scoring of FISH-"painted" chromosome-type exchange aberrations.

The effectiveness of FISH painting for easy detection of radiation-induced chromosome aberrations lies, principally, in the fact that only part of any exchange event is highlighted. However, this partial detection imposes certain limitations when the technique is applied to fundamental studies with primary aberrations, particularly at higher doses, when Complex exchanges are present. Some of these limitations are discussed in this paper.

Animals↗

PubMed2006

Does shade improve light interception efficiency? A comparison among seedlings from shade-tolerant and -intolerant temperate deciduous tree species.

Here, we tested two hypotheses: shading increases light interception efficiency (LIE) of broadleaved tree seedlings, and shade-tolerant species exhibit larger LIEs than do shade-intolerant ones. The impact of seedling size was taken into account to detect potential size-independent effects on LIE. LIE was defined as the ratio of mean light intercepted by leaves to light intercepted by a horizontal surface of equal area. Seedlings from five species differing in shade tolerance (Acer saccharum, Betula alleghaniensis, A. pseudoplatanus, B. pendula, Fagus sylvatica) were grown under neutral shading nets providing 36, 16 and 4% of external irradiance. Seedlings (1- and 2-year-old) were three-dimensionally digitized, allowing calculation of LIE. Shading induced dramatic reduction in total leaf area, which was lowest in shade-tolerant species in all irradiance regimes. Irradiance reduced LIE through increasing leaf overlap with increasing leaf area. There was very little evidence of significant size-independent plasticity of LIE. No relationship was found between the known shade tolerance of species and LIE at equivalent size and irradiance.

Microclimate↗

PubMed1978

The control region of the F sex factor DNA transfer cistrons: restriction mapping and DNA cloning.

A restriction endonuclease map of EcoRI fragment f6 of F sex factor DNA was constructed and aligned with pre-existing physical and genetic maps. Results of genetic complementation tests and analysis of proteins synthesized in minicells from PstI and BglII sub-fragment clones, or from a specific BglII fragment deletion, have allowed mapping of the locations of the origin of DNA transfer and many of the transfer genes known to lie on f6. The proteins detected account for 78% of the coding capacity of fragment f6.

Chromosome Mapping↗

PubMed2004

Use of tomographic nuclear medicine procedures, SPECT and pinhole SPECT, with cationic lipophilic radiotracers for the evaluation of axillary lymph node status in breast cancer patients.

Scintimammography with the cationic lipophilic (99m)Tc-tetrofosmin and (99m)Tc-methoxyisobutylisonitrile (MIBI) is one of the most widely available non-invasive imaging methods employed in the preoperative evaluation of breast cancer axillary lymph node status, for which, at present, axillary lymph node dissection (ALND) is still considered the method of choice. Comparative studies have demonstrated that single-photon emission computed tomography (SPECT) acquisition significantly improves the sensitivity and accuracy achieved with planar scintimammography, particularly when lymph nodes are non-palpable, small in size and limited in number. Thus, SPECT should be preferred to planar imaging, particularly in those patients without clinical suspicion of axillary metastatic involvement, given its high negative predictive value; however, false negative results have been reported due to the small size of lymph nodes and/or to partial or micrometastatic involvement. SPECT could also find clinical application in combination with radioguided sentinel lymph node (SLN) biopsy, providing additional useful information in selected cases. The performance of SPECT can be improved by using a pinhole collimator (pinhole SPECT), as recently demonstrated in comparative studies, and this method also determines the number of lymph nodes, thus delivering important prognostic information. Moreover, pinhole SPECT, the principal limitation of which (as with imaging methods) lies in its inability to detect micrometastases, has also proved capable of increasing the accuracy of radioguided SLN biopsy. However, only limited data relating to pinhole SPECT are available as yet, and clinical trials are necessary to validate its potential value.

Axilla↗

PubMed2004

FDG-PET for axillary lymph node staging in primary breast cancer.

Management of the axilla in patients with operable breast cancer is still one of the most controversial areas in clinical oncology. The best procedure to examine the lymph nodes is still standard axillary lymph node dissection; nevertheless, the morbidity associated with this procedure is well known. Based on these considerations, it is important for progress in the treatment of operable breast cancer that strategies are found that permit a less invasive method of axillary sampling which does not impair the patient's quality of life. The technique of sentinel lymph node (SLN) biopsy has recently been proposed for this purpose, with very important results. SLN has now become routine practice in the surgical management of breast cancer, and in many institutions patients with a negative SLN biopsy are spared axillary dissection, while those with a positive SLN biopsy are submitted to axillary node dissection. The good accuracy of SLN biopsy represents a significant advance in the management of primary breast cancer; however, false negative axillary results can occur in a variable percentage of patients, and the contribution of the SLN procedure to the detection of metastases in the internal mammary and supraclavicular lymph nodes is not clear. Among the recently developed imaging modalities, positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) has in particular been applied to the study of lymph node metastases in cancer patients. Several clinical studies have been carried out to evaluate the accuracy of PET in the axillary staging of operable primary breast cancer. These studies have sometimes provided conflicting results, either supporting the possibility of using FDG-PET to select patients who need axillary dissection or questioning whether FDG-PET can accurately assess the axillary status in primary breast cancer. All the limitations and the advantages of FDG-PET are discussed in this paper, by examining the performance of scanner technology and the possible causes of the false negative results. In the experience of the authors, comparing FDG-PET with SLN biopsy in the same series of patients, the results seem to indicate that the lower sensitivity of PET is restricted to micrometastases. Of course, this limitation of PET has to be analysed in relation to the importance of such small axillary metastases for the outcome of patients with breast cancer. The added value offered by PET in breast cancer staging in comparison with intraoperative detection of the sentinel node lies in the fact that FDG-PET is a non-invasive procedure that allows, within a single examination, the biological characterisation of breast cancer and viewing of the entire body.

Axilla↗

PubMed2001

Immunomagnetic enrichment of CD138 positive cells from weakly infiltrated myeloma patients samples enables the determination of the tumor clone specific IgH rearrangement.

In multiple myeloma, the polymerase chain reaction (PCR) of the Ig heavy chain with allele-specific oligonucleotide (ASO) primers is a common and well-described method of identifying the tumor clone in peripheral blood (PB), bone marrow (BM) or leukapheresis products (LA). A factor which is crucial to the detection of clonal Ig rearrangements lies in the 'purity' of the tumor tissue used for the consensus PCR. We describe the application of a method to enrich CD138 positive myeloma cells derived from weakly infiltrated PB-, BM- and LA-samples. These are subjected to immunomagnetic enrichment with the MACS system, using an CD138 antibody directly conjugated to magnetic beads to obtain an enriched tumor cell population and the subsequent amplification of tumor specific IgH rearrangements. We investigated 29 samples (ten PB, ten BM, nine LA) with a median myeloma cell content of 0.5%. The approach led to a median enrichment factor of 118. Tumor-specific rearrangements could be amplified reproducibly from samples containing less than 0.1% myeloma cells.

Consensus Sequence↗

PubMed1997

The determination of metals (antimony, bismuth, lead, cadmium, mercury, palladium, platinum, tellurium, thallium, tin and tungsten) in urine samples by inductively coupled plasma-mass spectrometry.

OBJECTIVE: An analytical method has been established to determine the concentration of antimony (Sb), bismuth (Bi), lead (Pb), cadmium (Cd), mercury (Hg), Palladium (Pd), platinum (Pt), tellurium (Te), tin (Sn), thallium (Tl) and tungsten (W) in urine. The aim was to develop a method which is equally suitable for the determination of environmentally as well as occupationally caused metal excretion. METHODS: Inductively coupled plasma-mass spectroscopy (ICP-MS) was used for the determination of metals. Calibration was done using aqueous solutions and standard addition respectively. RESULTS: Urine samples of 14 persons occupationally non-exposed to metals were analysed. With the exception of Pt and Bi all the metals were found in these urine samples. The detection limits for these metals lie between 5 and 50 ng/l. CONCLUSIONS: For some metals, which are important from an occupational as well as an environmental viewpoint, ICP-MS is more sensitive than atomic absorption spectrometry (AAS). ICP-MS, moreover, is welcome as a reference method for AAS with the additional advantage of multi-element measurement.

Adult↗

PubMed1981

Determination of apolipoprotein A-I by kinetic nephelometry.

Apolipoprotein A-I concentration in human serum was determined by kinetic nephelometry. Under optimal reaction conditions and within the normal physiological range the relation between apolipoprotein A-I concentration and measured rate units it approximately linear. The detection limit of the assay lies at 2 micrograms/ml. The coefficient of variation within one series is 1.44%. The correlation coefficient with alpha-cholesterol, as determined by agarose electrophoresis followed by polyanion precipitation, is better than 0.94. Addition of detergent to serum dilutions increases the reaction rate, suggesting that delipidation changes the antigenic expression of apolipoprotein A-I. The magnitude of this change is constant in normal controls, but not in special pathological cases. The described technique can be recommended for routine use in clinical chemistry for measurement of apolipoprotein A-I.

Animals↗

PubMed1981

Protein component from Drosophila larval nuclei showing sequence specificity for a short region near a major heat-shock protein gene.

Using a nitrocellulose filter binding assay we have detected a protein component in extracts prepared from the nuclei of D. melanogaster third instar larvae which shows sequence-specific binding to a short region on a cloned D. melanogaster DNA segment containing a copy of the major heat-shock protein gene. The specificity of binding was confirmed by direct visualization of the protein DNA complexes in the electron microscope. Protein blotting experiments demonstrated that three polypeptides in the extract were capable of such sequence-specific binding. The protein binding site detected in this cloned sequence lies 800-1000 bp upstream from the presumptive transcription start.

Animals↗

PubMed1988

The importance of resolution in the clinical application of breast sonography.

Although in use for over thirty years, breast ultrasound continues a steady evolution both in technological development and in clinical application. It is now firmly established as a first line diagnostic modality to be used in conjunction with x-ray mammography. Its ability to provide qualitatively different parenchymal information in a slice-type, or tomographic format with excellent resolution makes it a clinically important instrument. The ultimate goal, however, still lies ahead. This is the detection and characterization of small masses within the breast, coupled with the ability to determine whether these foci are benign or malignant. This will likely involve not only scanners with better resolution, but also those, such as doppler, with the ability to obtain functional information as well.

Adult↗

PubMed1989

Differential distribution of acetylcholinesterase activity among vasopressin- and oxytocin-containing supraoptic magnocellular neurons.

Acetylcholinesterase activity was demonstrated histochemically at light- and electron-microscopic levels, in Vibratome sections of the supraoptic nucleus of fixed hypothalami derived from osmotically stimulated and unstimulated Long Evans rats, from homozygous Brattleboro rats with hypothalamic diabetes insipidus, from lactating rats, from normal adult male house mice (Mus musculus) and from mice with hereditary nephrogenic diabetes insipidus (di/di). Reaction product was located in supraoptic magnocellular neurons; in dorsal and rostral aspects of the supraoptic nuclei lightly stained cells predominate, whereas in ventral and caudal regions densely staining perikarya predominate. Pre- and post-embedding immunocytochemical detection of oxytocin-neurophysin or vasopressin-neurophysin, combined with acetylcholinesterase histochemistry, showed that the lightly staining cells are oxytocinergic, and the densely staining cells vasopressinergic. Osmotic stimulation of the animals, either by substitution of drinking water for 3 days with 2.5% saline or reason of genetic defects which result in diabetes insipidus, enhanced the acetylcholinesterase activity of the vasopressin neurons but had little effect on the weekly acetylcholinesterase-reactive oxytocin cells. Acetylcholinesterase activity was particularly marked in the hypertrophied abnormal magnocellular neurons of homozygous Brattleboro rats which do not release significant amounts of vasopressin. The increased acetylcholinesterase activity in osmotically stimulated animals cannot, therefore, be a function of vasopressin. Acetylcholinesterase activity was also detected in large multipolar neurons lying dorsolateral to the supraoptic nucleus, and in their fine axonal processes which project towards the supraoptic nucleus. A very few synaptic boutons surrounded by acetylcholinesterase reaction product were found in contact with magnocellular neuron basal dendrites. However, much of the punctate acetylcholinesterase reactivity observed at the light microscopic level and previously interpreted as representing the loci of cholinergic synaptic boutons was shown to be intracellular, and probably caused by acetylcholinesterase activity in some large, secondary lysosomes.

Acetylcholinesterase↗

PubMed2004

Gynecologic ultrasound in emergency medicine.

The true value of ultrasound in acute abdominal pain lies in its ability to detect gynecologic disorders and effectively rule out other causes of acute abdominal pain that require surgical repair. Although the emergent gynecologic indications discussed in this article are few in number, this does not suggest that the nonpregnant patient presenting to the ED with abdominal pain should not receive an ultrasound examination. On the contrary, the author believes that in a "perfect world," ultrasound should be the initial imaging study in most of these patients. The reality is that it is difficult to convince radiology colleagues to call in a sonologist in the middle of the night for any indication other than ovarian torsion when CT scans can diagnose ovarian cysts and tubo-ovarian abscess. As was pointed out in the section on ovarian torsion, even adequate ovarian blood flow does not rule out this diagnosis.Ideally, an ultrasound of the pelvis could be undertaken at the time of the pelvic examination, adding as little as 5 to 10 minutes. If a gynecologic disorder could be confirmed, other imaging studies might be unnecessary,thereby reducing cost (potential savings on laboratory tests, cervical cultures, or CT scans), length of stay, and adverse complications of CT(contrast material reactions, and radiation exposure).Emergency medicine ultrasound continues to grow at a rapid pace. We are working toward a time when most EPs will be competent and comfortable performing bedside ultrasound examinations in a limited number of applications. The gynecologic application of ultrasound,however, requires skill beyond the level of the primary applications of emergency medicine ultrasound-specifically, mastering Doppler ultra-sound. Although ultrasound has proved to be a valuable imaging modality in the nonpregnant patient with acute abdominal pain when performed by a seasoned sonographer, the role of ED ultrasound has been limited to those EPs with significantly more training. The author believes that even limited expertise in gynecologic ultrasound is valuable in helping direct the management of these patients. Further research by skilled EP sonographers eventually will help define the role of EPs in this particular application of ultrasound. EPs should not be discouraged from developing expertise in this examination when a confirmatory study in radiology will be performed. Miles on the "ultrasound odometer" will not only sharpen sonographic skills but also will help the EP to better communicate with nonpregnant patients presenting with abdominal pain. There is a fairly specific barometer already in place to gauge one's gynecologic ultrasound skills: a seasoned EP sonographer never skips over the chart of a young woman with right lower quadrant pain.

Abscess↗

PubMed1989

Padé-Laplace method for analysis of fluorescence intensity decay.

This novel approach to the analysis of multiexponential functions is based on the combined use of the Laplace transform and Padé approximants (Yeramian, E., and P. Claverie. 1987. Nature (Lond.). 326:169-174). It is similar in principle to the well-known Isenberg method of moments (Isenberg, I. 1983. Biophys. J. 43:141-148) traditionally applied to the analysis of fluorescence decay. The advantage of the Padé-Laplace method lies in its ability to detect the number of components in a multiexponential function as well as their parameters. In this paper we modified the original method so that it can be applied to the analysis of multifrequency phase/modulation measurements of fluorescence decay. The method was tested first on simulated data. It afforded recovery up to four distinct lifetime components (and their fractional contributions). In the case of simulated data corresponding to continuous lifetime distributions (nonexponential decay), the results of the analysis by the Padé-Laplace method indicated the absence of discrete exponential components. The method was also applied to real phase/modulation data gathered on known fluorophores and their mixtures and on tryptophan fluorescence in phospholipase A2. The lifetime and fraction recoveries were consistent with those obtained from standard methods involving nonlinear least-square fitting.

Mathematics↗

PubMed1993

Child protection in schools: a survey of the training needs of Fife schoolteachers.

Teachers have an important role to play in child protection. This lies not only in the detection and reporting of possible cases of child abuse but also in multi-disciplinary teamwork, and in contributing to the ongoing support and monitoring of the abused child. Their role can only be properly carried out if teachers are equipped with the relevant skills. Appropriate in-service training in child protection for teachers is of key importance in both emphasising child protection issues and in promoting these skills in teachers. In order to guide the development of a training course for teachers in child protection, a survey of Fife teachers was carried out to investigate the knowledge, attitudes and practices of teachers with respect to a range of child protection issues. This confirmed that teachers consider child protection to be an important subject of direct relevance to their work as teachers. In-service training on this issue was almost unanimously welcomed. The study showed that although the knowledge of teachers regarding the signs of child abuse was reasonably good, in practice 40% of teachers did not feel confident in handling these issues. This has important implications for the design of training courses. Very few schools had established school child protection policies although the majority of teachers stated that such policies would be useful.

Child↗

PubMed2006

Effects of surface chemical composition on the early growth stages of alpha-sexithienyl films on silicon oxide substrates.

In organic field effect transistors, charge transport is confined to a narrow region next to the organic/dielectric interface. It is thus extremely important to determine the morphology and the molecular arrangement of the organic films at their early growth stages. On a substrate of technological interest, such as thermally grown silicon oxide, it has been recently found that alpha-sexithienyl aggregates made of flat-lying molecules can simultaneously nucleate besides islands made of molecules standing vertical. In this paper, we investigate the effects due to variations in surface chemical composition on alpha-sexithienyl ultrathin film formation. Flat-lying molecules are no longer detected when Si-OH groups present at the surface are chemically removed but also when the Si-OH or Si-H group density is maximized. This gives evidence that variations in the surface chemical composition can largely affect the nucleation and growth processes of organic/dielectric interfaces. We hypothesize that isolated OH groups can interact with alpha-sexithienyl molecules and anchor them down flat with respect to the surface.

Journal Article↗

PubMed2004

Methods for generating protein molecular ions in ToF-SIMS.

One of the greatest challenges in mass spectrometry lies in the generation and detection of molecular ions that can be used to directly identify the protein from the molecular weight of the molecular ion. Typically, proteins are large (MW > 1000), nonvolatile, and/or thermally labile, but the vaporization process produced by many mass spectrometry techniques including time-of-flight secondary ion mass spectrometry (ToF-SIMS) is inherently limited to generating ions from smaller compounds or fragments of the parent molecule, making the identification of proteins complex. The application of specific molecules to aid in the generation of high molecular weight ions in ToF-SIMS has been recognized for some time. In this study we have developed a matrix-SAM substrate preparation technique based on the self-assembly of a matrix-like molecule, mercaptonicotinic acid (MNA), on gold. We then compare this substrate with two existing ToF-SIMS sample preparation techniques, cationized alkane thiol and matrix-enhanced SIMS (MESIMS). The results of this study illustrate that while there is a range of methods that can be used to improve the molecular ion yield of proteins in ToF-SIMS, their efficacy and reproducibility vary considerably and crucially are linked to the sample preparation and/or protein application methods used. Critically, the MNA modified substrate was able to simultaneously induce molecular ions for each protein present in a multicomponent solution, suggesting that this sample preparation technique may have future application in proteomics and DNA analysis.

Gold↗

PubMed2000

Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome.

Griscelli syndrome (GS, MIM 214450), a rare, autosomal recessive disorder, results in pigmentary dilution of the skin and the hair, the presence of large clumps of pigment in hair shafts and an accumulation of melanosomes in melanocytes. Most patients also develop an uncontrolled T-lymphocyte and macrophage activation syndrome (known as haemophagocytic syndrome, HS), leading to death in the absence of bone-marrow transplantation. In contrast, early in life some GS patients show a severe neurological impairment without apparent immune abnormalities. We previously mapped the GS locus to chromosome 15q21 and found a mutation in a gene (MYO5A) encoding a molecular motor in two patients. Further linkage analysis suggested a second gene associated with GS was in the same chromosomal region. Homozygosity mapping in additional families narrowed the candidate region to a 3.1-cM interval between D15S1003 and D15S962. We detected mutations in RAB27A, which lies within this interval, in 16 patients with GS. Unlike MYO5A, the GTP-binding protein RAB27A appears to be involved in the control of the immune system, as all patients with RAB27A mutations, but none with the MYO5A mutation, developed HS. In addition, RAB27A-deficient T cells exhibited reduced cytotoxicity and cytolytic granule exocytosis, whereas MYO5A-defective T cells did not. RAB27A appears to be a key effector of cytotoxic granule exocytosis, a pathway essential for immune homeostasis.

B-Lymphocytes↗