Objective analysis of gait coordination for total knee arthroplasty outcome

Introduction: Coordination is a strategy chosen by the central nervous system to control the movements and maintain stability during gait. Coordinated multi-joint movements require a complex interaction between nervous outputs, biomechanical constraints, and pro-prioception. Quantitatively understanding and modeling gait coordination still remain a challenge. Surgeons lack a way to model and appreciate the coordination of patients before and after surgery of the lower limbs. Patients alter their gait patterns and their kinematic synergies when they walk faster or slower than normal speed to maintain their stability and minimize the energy cost of locomotion. The goal of this study was to provide a dynamical system approach to quantitatively describe human gait coordination and apply it to patients before and after total knee arthroplasty. Methods: A new method of quantitative analysis of interjoint coordination during gait was designed, providing a general model to capture the whole dynamics and showing the kinematic synergies at various walking speeds. The proposed model imposed a relationship among lower limb joint angles (hips and knees) to parameterize the dynamics of locomotion of each individual. An integration of different analysis tools such as Harmonic analysis, Principal Component Analysis, and Artificial Neural Network helped overcome high-dimensionality, temporal dependence, and non-linear relationships of the gait patterns. Ten patients were studied using an ambulatory gait device (Physilog®). Each participant was asked to perform two walking trials of 30m long at 3 different speeds and to complete an EQ-5D questionnaire, a WOMAC and Knee Society Score. Lower limbs rotations were measured by four miniature angular rate sensors mounted respectively, on each shank and thigh. The outcomes of the eight patients undergoing total knee arthroplasty, recorded pre-operatively and post-operatively at 6 weeks, 3 months, 6 months and 1 year were compared to 2 age-matched healthy subjects. Results: The new method provided coordination scores at various walking speeds, ranged between 0 and 10. It determined the overall coordination of the lower limbs as well as the contribution of each joint to the total coordination. The difference between the pre-operative and post-operative coordination values were correlated with the improvements of the subjective outcome scores. Although the study group was small, the results showed a new way to objectively quantify gait coordination of patients undergoing total knee arthroplasty, using only portable body-fixed sensors. Conclusion: A new method for objective gait coordination analysis has been developed with very encouraging results regarding the objective outcome of lower limb surgery.

NAVA enhances tidal volume and diaphragmatic electro-myographic activity matching: a Range90 analysis of supply and demand.

Neurally adjusted ventilatory assist (NAVA) is a ventilation assist mode that delivers pressure in proportionality to electrical activity of the diaphragm (Eadi). Compared to pressure support ventilation (PS), it improves patient-ventilator synchrony and should allow a better expression of patient's intrinsic respiratory variability. We hypothesize that NAVA provides better matching in ventilator tidal volume (Vt) to patients inspiratory demand. 22 patients with acute respiratory failure, ventilated with PS were included in the study. A comparative study was carried out between PS and NAVA, with NAVA gain ensuring the same peak airway pressure as PS. Robust coefficients of variation (CVR) for Eadi and Vt were compared for each mode. The integral of Eadi (ʃEadi) was used to represent patient's inspiratory demand. To evaluate tidal volume and patient's demand matching, Range90 = 5-95 % range of the Vt/ʃEadi ratio was calculated, to normalize and compare differences in demand within and between patients and modes. In this study, peak Eadi and ʃEadi are correlated with median correlation of coefficients, R > 0.95. Median ʃEadi, Vt, neural inspiratory time (Ti_ ( Neural )), inspiratory time (Ti) and peak inspiratory pressure (PIP) were similar in PS and NAVA. However, it was found that individual patients have higher or smaller ʃEadi, Vt, Ti_ ( Neural ), Ti and PIP. CVR analysis showed greater Vt variability for NAVA (p < 0.005). Range90 was lower for NAVA than PS for 21 of 22 patients. NAVA provided better matching of Vt to ʃEadi for 21 of 22 patients, and provided greater variability Vt. These results were achieved regardless of differences in ventilatory demand (Eadi) between patients and modes.

Chirality in the new generation of antidepressants: stereoselective analysis of the enantiomers of mirtazapine, N-demethylmirtazapine, and 8-hydroxymirtazapine by LC-MS.

Mirtazapine is an antidepressant that acts specifically on noradrenergic and sertonergic receptors. A LC-MS method was developed that allows the simultaneous analysis of the R-(-)- and S-(+)-enantiomers of mirtazapine (MIR), demethylmirtazapine (DMIR), and 8-hydroxymirtazapine (8-OH-MIR) in plasma of MIR-treated patients. The method involves a 3-step liquid-liquid extraction, an HPLC separation on a Chirobiotic V column, and MS detection in electrospray mode. The limit of quantification (LOQ) for all enantiomers was 0.5 ng/mL, and the intra- and interday CVs were within 3.3% to 11.7% (concentration ranges 5-50 ng/mL). A method is also presented for the quantitative analysis of glucuroconjugated MIR and 8-OH-MIR. S-(+)-8-OH-MIR is present in plasma mainly as its glucuronide. Preliminary data suggest that in all patients, except in those comedicated with CYP2D6 inhibitors such as fluoxetine and thioridazine, R-(-)-MIR concentrations were higher than those of S-(+)MIR. Moreover, fluvoxamine seems also to inhibit the metabolism of MIR. Therefore, this method seems to be suitable for the stereoselective assay of MIR and its metabolites in plasma of patients comedicated with MIR and other drugs for routine and research purposes.

Genome-wide association analysis identifies 20 loci that influence adult height.

Adult height is a model polygenic trait, but there has been limited success in identifying the genes underlying its normal variation. To identify genetic variants influencing adult human height, we used genome-wide association data from 13,665 individuals and genotyped 39 variants in an additional 16,482 samples. We identified 20 variants associated with adult height (P < 5 x 10(-7), with 10 reaching P < 1 x 10(-10)). Combined, the 20 SNPs explain approximately 3% of height variation, with a approximately 5 cm difference between the 6.2% of people with 17 or fewer 'tall' alleles compared to the 5.5% with 27 or more 'tall' alleles. The loci we identified implicate genes in Hedgehog signaling (IHH, HHIP, PTCH1), extracellular matrix (EFEMP1, ADAMTSL3, ACAN) and cancer (CDK6, HMGA2, DLEU7) pathways, and provide new insights into human growth and developmental processes. Finally, our results provide insights into the genetic architecture of a classic quantitative trait.

Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa.

Autosomal recessive cutis laxa type I (ARCL type I) is characterized by generalized cutis laxa with pulmonary emphysema and/or vascular complications. Rarely, mutations can be identified in FBLN4 or FBLN5. Recently, LTBP4 mutations have been implicated in a similar phenotype. Studying FBLN4, FBLN5, and LTBP4 in 12 families with ARCL type I, we found bi-allelic FBLN5 mutations in two probands, whereas nine probands harbored biallelic mutations in LTBP4. FBLN5 and LTBP4 mutations cause a very similar phenotype associated with severe pulmonary emphysema, in the absence of vascular tortuosity or aneurysms. Gastrointestinal and genitourinary tract involvement seems to be more severe in patients with LTBP4 mutations. Functional studies showed that most premature termination mutations in LTBP4 result in severely reduced mRNA and protein levels. This correlated with increased transforming growth factor-beta (TGFβ) activity. However, one mutation, c.4127dupC, escaped nonsense-mediated decay. The corresponding mutant protein (p.Arg1377Alafs(*) 27) showed reduced colocalization with fibronectin, leading to an abnormal morphology of microfibrils in fibroblast cultures, while retaining normal TGFβ activity. We conclude that LTBP4 mutations cause disease through both loss of function and gain of function mechanisms.

Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts.

BACKGROUND: American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but without specifying the impact of different thyroid-stimulation hormone (TSH) levels. Limited prospective data exist on the association between subclinical thyroid dysfunction and heart failure events. METHODS AND RESULTS: We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of heart failure events. Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L, subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L, and subclinical hyperthyroidism as TSH <0.45 mIU/L, the last two with normal free thyroxine levels. Among 25 390 participants, 2068 (8.1%) had subclinical hypothyroidism and 648 (2.6%) had subclinical hyperthyroidism. In age- and sex-adjusted analyses, risks of heart failure events were increased with both higher and lower TSH levels (P for quadratic pattern <0.01); the hazard ratio was 1.01 (95% confidence interval, 0.81-1.26) for TSH of 4.5 to 6.9 mIU/L, 1.65 (95% confidence interval, 0.84-3.23) for TSH of 7.0 to 9.9 mIU/L, 1.86 (95% confidence interval, 1.27-2.72) for TSH of 10.0 to 19.9 mIU/L (P for trend <0.01) and 1.31 (95% confidence interval, 0.88-1.95) for TSH of 0.10 to 0.44 mIU/L and 1.94 (95% confidence interval, 1.01-3.72) for TSH <0.10 mIU/L (P for trend=0.047). Risks remained similar after adjustment for cardiovascular risk factors. CONCLUSION: Risks of heart failure events were increased with both higher and lower TSH levels, particularly for TSH ≥10 and <0.10 mIU/L.

Microfacies analysis of the lower paleocene beda formation in Western Concession 59 and Block 59F, Sirte Basin, Libya /

The rock sequence of the Tertiary Beda Formation of S. W. concession 59 and 59F block in Sirte Basin of Libya has been subdivided into twelve platformal carbonate microfacies. These microfacies are dominated by muddy carbonates, such as skeletal mudstones, wackestones, and packstones with dolomites and anhydrite. Rock textures, faunal assemblages and sedimentary structures suggest shallow, clear, warm waters and low to moderate energy conditions within the depositional shelf environment. The Beda Formation represents a shallowing-upward sequence typical of lagoonal and tidal flat environments marked at the top by sabkha and brackish-water sediments. Microfossils include benthonic foraminifera, such as miliolids, Nummulites, - oerculina and other smaller benthonics, in addition to dasycladacean algae, ostracods, molluscs, echinoderms, bryozoans and charophytes. Fecal pellets and pelloids, along with the biotic allochems, contributed greatly to the composition of the various microfacies. Dolomite, where present, is finely crystalline and an early replacement product. Anhydrite occurs as nodular, chickenwire and massive textures indicating supratidal sabkha deposition. Compaction, micr it i zat ion , dolomit izat ion , recrystallization, cementation, and dissolution resulted in alteration and obliteration of primary sedimentary structures of the Beda Formation microfacies. The study area is located in the Gerad Trough which developed as a NE-SW trending extensional graben. The Gerad trough was characterized by deep-shallow water conditions throughout the deposition of the Beda Formation sediments. The study area is marked by several horsts and grabens; as a result of extent ional tectonism. The area was tectonically active throughout the Tertiary period. Primary porosity is intergranular and intragranular, and secondary processes are characterized by dissolution, intercrystalline, fracture and fenestral features. Diagenesis, through solution leaching and dolomitization, contributed greatly to porosity development. Reservoir traps of the Beda Formation are characterized by normal fault blocks and the general reservoir characteristics/properties appear to be facies controlled.

Secretory immunity in overweight and obese versus normal-weight early-and late-pubertal females

Obesity is a condition associated with a wide variety of health problems including hypertension, dyslipidemia, diabetes mellitus, certain forms of cancer, cardiovascular disease, and gallstones (157). TTiere is growing evidence that obesity may also be related to compromised immune function due to altered metabolic, psychological, and physical attributes (93). The aim of this study was to compare: a) immunity-related variables such as frequency of upper respiratory tract infections (URTI) and salivary secretory immunoglobulin A (sIgA) levels between overweight/obese (OB) and normal weight (NW) early-pubertal and late-pubertal girls, and b) stress-related variables such as Cortisol, melatonin, the melatonin/cortisol ratio, testosterone and the testosterone/cortisol ratio. Physical activity levels, stress indicators, and fatigue were used to explain potential differences in the dependent variables. It was hypothesized that the OB females would have lower melatonin (M) and higher Cortisol (C) and testosterone (T) levels compared with NW girls, regardless of maturity status. The altered levels of melatonin, Cortisol, and testosterone, would result in decreased M/C and T/C ratios, despite the increase in testosterone in OB females. It was hypothesized that this altered hormonal status results in a compromised immunity marked by higher frequency of upper respiratory tract infections (URTI) and decreased levels of secretory immunoglobulin A (sIgA). It was also hypothesized that OB girls would participate in less hours of physical activity than their NW counterparts and that this would relate to their stress and immunity levels. Forty (16 early- and 24 late-pubertal) overweight and obese females were compared to fifty-three (27 eariy- and 26 late-pubertal) age-matched normal-weight control subjects. Participants were categorized as early-pubertal (EP) or late-pubertal (LP) using Tanner self-staging of secondary sex characteristics. Subjects were classified into the two adiposity groups according to relative body fat (%BF), where normal weight (NW) subjects had a %BF less than 25%, and overweight and obese (OB) subjects had a %BF greater than 27.5%. Participants completed a number of questionnaires and information was collected on menstrual history, smoking history, alcohol and caffeine consumption, and medical history. Following the determination of maturity status, a complete anthropometric assessment was made including height, body mass, and body composition. All questionnaires and measurements were completed during a one-hour visit between 1 500 and 1900 hours Relative body fat was assessed using bioelectrical impedance analysis. Resting saliva samples were obtained and assayed (ELISA) for testosterone, Cortisol, melatonin and secretory immunoglobulin A. Physical activity was self-reported using the Godin- Shephard Leisure time questionnaire, and quantified using Actigraph GTIM accelerometers, which participants wore for seven consecutive days from the time they woke up in the morning, until the time they went to bed. Late-pubertal girls also completed questionnaires on their perceived stress and fatigue. Finally, all participants also filled out a one-month health log to record frequency of symptoms of upper respiratory tract infections (URTI). Significant age effects were found for testosterone, Cortisol, incidence of sickness, and sIgA when controlling for physical activity, however there were no significant effects of adiposity on any of the variables. There was a trend which neared-significance for an effect of adiposity on sIgA (p=0.01). There were no significant differences between the groups on the total selfreported leisure-time physical activity in METs per week, however EP girls recorded significantly greater levels of moderate, hard, and very hard physical activity from accelerometers. Results of the perceived stress and fatigue questionnaires in late-pubertal girls demonstrated that contrary to what was hypothesized, NW girls reported more stress and more fatigue than OB girls. Results of the present study suggest that excess adiposity in early- and latepubescent girls may not have a negative impact on immunity as hypothesized.

Crystal growth, Raman scattering and optical properties of the superconductor Cd2Re2O7(16O, 18O)/

Using the Physical Vapor Transport method, single crystals of Cd2Re207 have been grown, and crystals of dimensions up to 8x6x2 mm have been achieved. X-ray diffraction from a single crystal of Cd2Re207 has showed the crystal growth in the (111) plane. Powder X-ray diffraction measurements were performed on ^^O and ^^O samples, however no difference was observed. Assigning the space group Fd3m to Cd2Re207 at room temperature and using structure factor analysis, the powder X-ray diffraction pattern of the sample was explained through systematic reflection absences. The temperatiure dependence of the resistivity measurement of ^^O has revealed two structural phase transitions at 120 and 200 K, and the superconducting transition at 1.0 K. Using Factor Group Analysis on three different structiures of Cd2Re207, the number of IR and Raman active phonon modes close to the Brillouin zone centre have been determined and the results have been compared to the temperature-dependence of the Raman shifts of ^^O and ^*0 samples. After scaling (via removing Bose-Einstein and Rayleigh scattering factors from the scattered light) all spectra, each spectrum was fitted with a number of Lorentzian peaks. The temperature-dependence of the FWHM and Raman shift of mode Eg, shows the effects of the two structurjil phase transitions above Tc. The absolute reflectance of Cd2Re207 - '^O single crystals in the far-infrared spectral region (7-700 cm~^) has been measured in the superconducting state (0.5 K), right above the superconducting state (1.5 K), and in the normal state (4.2 K). Thermal reflectance of the sample at 0.5 K and 1.5 K indicates a strong absorption feature close to 10 cm~^ in the superconducting state with a reference temperature of 4.2 K. By means of Kramers-Kronig analysis, the absolute reflectance was used to calculate the optical conductivity and dielectric function. The real part of optical conductivity shows five distinct active phonon modes at 44, 200, 300, 375, and 575 cm~' at all temperatures including a Drude-like behavior at low frequencies. The imaginary part of the calculated dielectric function indicates a mode softening of the mode 44 cm~' below Tc.

The association between body composition and arterial stiffness in peri-pubescent children

The objective of this study was to examine the association between body composition and arterial stiffuess in peri-pubescent boys and girls. Differences in arterial distensibility were measured in 68 children (45 normal weight, 12 overweight, and 11 obese) between the ages of9 to 12 years. Weight classification was based on age and gender-specific body mass index cut-offs, while pubertal maturation was self-reported using Tanner staging. Distensibility was determined using two-dimensional, B-Mode echo Doppler ultrasound to measure changes at the right common carotid artery (CCA) diameter changes, while carotid pulse pressure (cPP) was measured at the left CCA by applanation tonometry. One-way ANOV A analysis revealed significant differences (p<0.001) in all anthropometric measures between the normal weight and overweight children, as well as the normal weight and obese children. Body stature was only higher in obese children compared to normal weight children (p<0.01). No significant differences were found between groups regarding age or Tanner stage. Common carotid artery distensibility showed a significant difference (p<0.01) between normal weight children (0.008 ± 0.002 mmHg-1 ) compared to obese children (0.005 ± 0.002 mmHg-1 ), with a borderline significant difference between the normal and overweight subjects (p=0.06). There was no significant effect for gender between males and females across all independent variables. The strongest determinants of distensibility in children were cPP (r= -0.52, panalysis revealed that cPP alone explained 27% of the variance in distensibility in children. In addition, cPP, diameter difference, systolic and diastolic diameter, as well as waist-to-hip ratio explained 94% of the variance among peri-pubescent children. This study greatly underscores the need for weight management for long-term prevention of cardiovascular disease in overweight and obese children.

A comparison of electrophysiological changes during the sleep onset period of psychophysiological insomniacs, psychiatric insomniacs and normal sleepers

The EEG of the sleep onset period of psychophysiological insomniacs, psychiatric insomniacs and controls was compared using power spectral analysis (FFT). Eighteen drug-free subjects were equally divided into three groups according to their responses in the Brock Sleep and Insomnia Questionnaire, the Minnesota Multiphasic Personality Inventory and the Sleep Disorders Questionnaire. Group 1 consisted of psychophysiological insomniacs, group 2 included insomniacs with an indication of psychiatric disturbances, and group 3 was a control group. EEG, EOG and EMG were recorded for two consecutive nights. Power spectral analysis (FFT) of EEG at C4 from the sleep onset period (defined as lights out to the first five minutes of stage 2) was performed on all standard frequency bands, delta: .5-4 Hz; theta: 4-8 Hz; alpha: 8-12 Hz; sigma: 12-15 Hz beta: 15-25 Hz. Psychophysiological insomniacs had less alpha during wakefulness than the other two groups and did not show the dramatic drop in alpha across the sleep onset period, which characterizes normal sleep. They also had less delta, especially during stage 2 on night 2. They also showed less delta in the last quartile of the chronological analysis of the sleep onset period. Psychiatric insomniacs showed lower relative beta power values overall while psychophysiological insomniacs showed higher relative beta power values during wakefulness. This microanalysis 11 confirms that the sleep onset period is generally similar for psychiatric insomniacs and normal sleepers. This may be due to the sample of psychiatric insomniacs being heterogeneous or may reflect a sleep onset system that is essentially intact. Psychophysiological insomniacs have higher cortical arousal during the sleep onset period than do the psychiatric insomniacs and the controls. Clear differences in the sleep onset period of psychophysiological insomniacs exist. The dramatic changes in power values in these two groups are not seen in the psychophysiological insomniacs, which may make the discrimination between wakefulness and sleep more difficult.

The cloning and reconstitution of a bovine adenovirus type 2 E3 deletion mutant and the sequencing and analysis of the early 4 region

Recombinant Adenoviruses (Ads) have been shown to have potential applications in three areas: gene therapy, high level protein expression and recombinant vaccines.' At least three different locations within the Ad genome can be deleted and subsequently used for the insertion of foreign sequences. These include the Early 3 (E3), Early 1 (E1) and Early 4 (E4) regions. Viral vectors of this type have been well studied in Human Ads 2 and 5, however one has not yet been constructed for Bovine Adenovirus Type 2 (BAV2). The E3 region is located between 76.6 and 86 m.u. on the r-strand and is transcribed in a rightward direction. The gene products of the Early 3 region (E3) have been shown to be non-essential for viral replication, in vitro, but are required for host immunosurveillance. This study represents the cloning and reconstitution of a BAV2 E3 deletion mutant. A deletion of 1800bp was made within the E3 region of BAV2 and the thymidine kinase gene was subsequently inserted in the deleted area . . The plasmid pdlE3-4tk1 (23.4Kbp) was constructed and used to to facilitate homologous recombination with the wild type BAV2 to produce a mutant. Southern Blotting and Hybridization results suggest the presence of a BAV2 E3 deletion mutant with thymidine kinase sequences present. The E4 region of Human Adenovirus types 2 and 5 is located at the extreme right end of the genome (91.3 map units - 99.1 map units) and is transcribed in a leftward direction giving rise to a complicated set of differentially spliced mRNAs. Essentially there are 7 open reading frames (ORFs) encoding for at least 7 polypeptides. The gene products encoded by the E4 region have been shown to be essential for the expression of late viral genes, host cell shutoff and normal viral growth. We have cloned and sequenced the right end segment between 90.5 map units and 100 map units of the BAV2 genome. The results show several open reading frames which encode polypeptides exhibiting homology to three polypeptides encoded by the E4 region of human adenovirus type 2. These include the 14kDa protein encoded by ORF1, the 34kDa protein encoded by ORF6 and the 13kDa protein encoded by ORF3. The nucleotide sequence, restriction enzyme map, and ORF map of the E4 region could be very useful in future molecular manipulation of this region and could possibly explain the slow growth rate of BAV2 in MDBK cells.

The fast atom bombardment mass spectrometric analysis of the carbamate pesticide carbaryl

The carbamate pesticide, carbaryl, was quantitatively studied using fast atom bombardment mass spectrometry (FAB-MS). Mass spectra were obtained in the positive ion-mode using both 2-nitrophenyloctyl ether (NPOE) and 3-nitrobenzyl alcohol (NBA) as matrix liquids. The sample was applied by three different techniques; simple mixing, solvent mixing and surface precipitation. Smaller volumes of matrix liquid were found to produce more favourable ion currents. Detection limits were largely independent of the matrix or application technique used. The relationship between ion current and the mass of analyte was found to be intricately related to the choice of matrix liquid.

Development and characterization of concentric capillary nebulizer used in inductively coupled plasma analysis /

A simple, low-cost concentric capillary nebulizer (CCN) was developed and evaluated for ICP spectrometry. The CCN could be operated at sample uptake rates of 0.050-1.00 ml min'^ and under oscillating and non-oscillating conditions. Aerosol characteristics for the CCN were studied using a laser Fraunhofter diffraction analyzer. Solvent transport efficiencies and transport rates, detection limits, and short- and long-term stabilities were evaluated for the CCN with a modified cyclonic spray chamber at different sample uptake rates. The Mg II (280.2nm)/l\/lg 1(285.2nm) ratio was used for matrix effect studies. Results were compared to those with conventional nebulizers, a cross-flow nebulizer with a Scott-type spray chamber, a GemCone nebulizer with a cyclonic spray chamber, and a Meinhard TR-30-K3 concentric nebulizer with a cyclonic spray chamber. Transport efficiencies of up to 57% were obtained for the CCN. For the elements tested, short- and long-term precisions and detection limits obtained with the CCN at 0.050-0.500 ml min'^ are similar to, or better than, those obtained on the same instrument using the conventional nebulizers (at 1.0 ml min'^). The depressive and enhancement effects of easily ionizable element Na, sulfuric acid, and dodecylamine surfactant on analyte signals with the CCN are similar to, or better than, those obtained with the conventional nebulizers. However, capillary clog was observed when the sample solution with high dissolved solids was nebulized for more than 40 min. The effects of data acquisition and data processing on detection limits were studied using inductively coupled plasma-atomic emission spectrometry. The study examined the effects of different detection limit approaches, the effects of data integration modes, the effects of regression modes, the effects of the standard concentration range and the number of standards, the effects of sample uptake rate, and the effect of Integration time. All the experiments followed the same protocols. Three detection limit approaches were examined, lUPAC method, the residual standard deviation (RSD), and the signal-to-background ratio and relative standard deviation of the background (SBR-RSDB). The study demonstrated that the different approaches, the integration modes, the regression methods, and the sample uptake rates can have an effect on detection limits. The study also showed that the different approaches give different detection limits and some methods (for example, RSD) are susceptible to the quality of calibration curves. Multicomponents spectral fitting (MSF) gave the best results among these three integration modes, peak height, peak area, and MSF. Weighted least squares method showed the ability to obtain better quality calibration curves. Although an effect of the number of standards on detection limits was not observed, multiple standards are recommended because they provide more reliable calibration curves. An increase of sample uptake rate and integration time could improve detection limits. However, an improvement with increased integration time on detection limits was not observed because the auto integration mode was used.

Fitness to stand trial : how discourses of rationality, reasonableness and culpability inform the law and psychiatry to create standards of normal

The objective of this thesis is to demonstrate the importance of the concepts of rationality, reasonableness, culpability and autonomy that inform and support our conception of both the person and the punishable subject. A critical discourse analysis tracing these concepts through both the law and psychological tools used to evaluate the fitness of a person reveals that these concepts and their implied values are inconsistently applied to the mentally disordered who come into conflict with the law. I argue that the result of this inconsistency compromises a person's autonomy which is a contradiction to this concept as a foundational principle of the law. Ultimately, this thesis does not provide a solution to be employed in policy making, but its analysis leaves open possibilities for further exploration into the ways legal and social justice can be reconciled.