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Biomedical subjects

J R Williams

Publications and source records attributed to J R Williams.

At least 19 recordsLinked to original sources

Simulating long-term and residual effects of nitrogen fertilization on corn yields, soil carbon sequestration, and soil nitrogen dynamics.

Soil carbon sequestration (SCS) has the potential to attenuate increasing atmospheric CO2 and mitigate greenhouse warming. Understanding of this potential can be assisted by the use of simulation models. We evaluated the ability of the EPIC model to simulate corn (Zea mays L.) yields and soil organic carbon (SOC) at Arlington, WI, during 1958-1991. Corn was grown continuously on a Typic Argiudoll with three N levels: LTN1 (control), LTN2 (medium), and LTN3 (high). The LTN2 N rate started at 56 kg ha(-1) (1958), increased to 92 kg ha(-1) (1963), and reached 140 kg ha(-1) (1973). The LTN3 N rate was maintained at twice the LTN2 level. In 1984, each plot was divided into four subplots receiving N at 0, 84, 168, and 252 kg ha(-1). Five treatments were used for model evaluation. Percent errors of mean yield predictions during 1958-1983 decreased as N rate increased (LTN1 = -5.0%, LTN2 = 3.5%, and LTN3 = 1.0%). Percent errors of mean yield predictions during 1985-1991 were larger than during the first period. Simulated and observed mean yields during 1958-1991 were highly correlated (R2 = 0.961, p < 0.01). Simulated SOC agreed well with observed values with percent errors from -5.8 to 0.5% in 1984 and from -5.1 to 0.7% in 1990. EPIC captured the dynamics of SOC, SCS, and microbial biomass. Simulated net N mineralization rates were lower than those from laboratory incubations. Improvements in EPIC's ability to predict annual variability of crop yields may lead to improved estimates of SCS.

Biomass↗

What is the achievable effectiveness of the India AIDS Initiative intervention among female sex workers under target coverage? Model projections from southern India.

BACKGROUND: The India AIDS Initiative (Avahan) prevention programme funded by the Bill and Melinda Gates Foundation aims to reduce HIV prevalence in high risk groups such as female and male sex workers and their clients, to limit HIV transmission in the general population. OBJECTIVES: To assess the potential effectiveness of the Avahan intervention at the level of coverage targeted, in different epidemiological settings in India. METHODS: A deterministic compartmental model of the transmission dynamics of HIV and two sexually transmitted infections, and sensitivity analysis techniques, were used, in combination with available behavioural and epidemiological data from Mysore and Bagalkot districts in the Indian state of Karnataka, to evaluate the syndromic sexually transmitted infection (STI) management (STI treatment), periodic presumptive treatment of STI (PPT), and condom components of the Avahan intervention targeted to female sex workers (FSW). RESULTS: If all components of the intervention reach target coverage (that is, PPT, STI treatment and condom use), the intervention is expected to prevent 22-35% of all new HIV infections in FSW and in the total population over 5 years in a low transmission setting like Mysore, and to be half as effective in high transmission settings such as Bagalkot. The results were sensitive to small variations in intervention coverage. The condom component alone is expected to prevent around 20% of all new HIV infections over 5 years in Mysore and around 6% for the STI component alone; compared with 7%-14% for the PPT component alone. Multivariate sensitivity analyses suggested that interventions may be more effective in settings with low FSW HIV prevalence and small FSW populations, whereas HIV prevalence was most influenced by sexual behaviour and condom use parameters for FSW. CONCLUSION: The Avahan intervention is expected to be effective. However, to be able to demonstrate effectiveness empirically in the different settings, it is important to achieve target coverage or higher, which in the case of PPT could take a number of years to achieve. These preliminary model predictions need to be validated with more detailed mathematical models, as better data on sexual behaviour, condom use, STI and HIV trends over time, and intervention coverage data accumulate over the course of the programme.

Acquired Immunodeficiency Syndrome↗

Vascular endothelial growth factor receptors in osteoclast differentiation and function.

Osteoclasts are derived from haematopoietic stem cell precursors of the monocyte/macrophage cell lineage, through interaction with factors that are believed to include M-CSF and RANKL. VEGF is a proangiogenic cytokine that has been shown to promote osteoclast differentiation and survival. In this study, we assessed the role of VEGF and its receptors in osteoclastogenesis, in vitro, by culturing osteoclast precursors in the presence of VEGF, VEGF receptor-specific ligands, and blocking antibodies to VEGF receptors. Activation of VEGFR1 in the presence of RANKL induces osteoclast differentiation. Stimulating the receptors individually induced increased resorption by osteoclasts compared to controls but not to the level observed when stimulating both receptors simultaneously. We have shown that VEGF induces osteoclast differentiation through its action on VEGFR1. The way in which VEGF mediates its effect on mature osteoclast activity, however, may be through its interaction with both receptor subtypes.

Bone Resorption↗

Vascular endothelial growth factor acts as an osteolytic factor in breast cancer metastases to bone.

Vascular endothelial growth factor (VEGF) is a proangiogenic cytokine that is expressed highly in many solid tumours often correlating with a poor prognosis. In this study, we investigated the expression of VEGF and its receptors in bone metastases from primary human breast tumours and further characterised its effects on osteoclasts in vitro. Breast cancer metastases to bone were immunohistochemically stained for VEGF, its receptors VEGFR1 and 2 (vascular endothelial growth factor receptor 1 and 2), demonstrating that breast cancer metastases express VEGF strongly and that surrounding osteoclasts express both VEGFR1 and VEGFR2. RAW 264.7 cells (mouse monocyte cell line) and human peripheral blood mononuclear cells (PBMCs) were cultured with VEGF, RANKL and M-CSF. VEGF and RANKL together induced differentiation of multinucleated, tartrate-resistant acid phophatase (TRAP)-positive cells in similar numbers to M-CSF and RANKL. The PBMCs were also able to significantly stimulate resorption of mineralised matrix after treatment with M-CSF with RANKL and VEGF with RANKL. We have shown that VEGF in the presence of RANKL supports PBMC differentiation into osteoclast-like cells, able to resorb substrate. Vascular endothelial growth factor may therefore play a role in physiological bone resorption and in pathological situations. Consequently, VEGF signalling may be a therapeutic target for osteoclast inhibition in conditions such as tumour osteolysis.

Adult↗

Measles elimination in Italy: projected impact of the National Elimination Plan.

A mathematical model was used to evaluate the impact of the Italian Measles National Elimination Plan (NEP), and possible sources of failure in achieving its targets. The model considered two different estimates of force of infection, and the possible effect on measles transmission of the current Italian demographic situation, characterized by a below-replacement fertility. Results suggest that reaching all NEP targets will allow measles elimination to be achieved. In addition, the model suggests that achieving elimination by reaching a 95 % first-dose coverage appears unlikely; and that conducting catch-up activities, reaching high vaccination coverage, could interrupt virus circulation, but could not prevent the infection re-emerging before 2020. Also, the introduction of the second dose of measles vaccine seems necessary for achieving and maintaining elimination. Furthermore, current Italian demography appears to be favourable for reaching elimination.

Child↗

Impaired forearm rotation after tension-band-wiring fixation of olecranon fractures: evaluation of the transcortical K-wire technique.

The tension-band-wiring technique is a well-accepted method of internal fixation of olecranon fractures. In addition, it is suggested that transcortical placement of the k-wires results in lower rates wire migration. We encountered two clinical cases in which transcortical placement of the k-wires led to impairment of forearm rotation. An anatomic study was conducted to study the effect of transcortical wire placement to avoid similar future complications. Using specimens from 10 embalmed cadavers, we found that transcortical wires inserted in <30 degrees of ulnar angulation in the coronal plane to the medial ridge of the olecranon, impinged on the radial neck, supinator muscle, or biceps tendon. This was avoided in all 10 specimens when the wires were inserted, with the forearm in supination, at 30 degrees of ulnar angulation. We recommend this technique to be adopted to avoid forearm rotation impairment.

Bone Wires↗

In vivo mammary tumourigenesis in the Sprague-Dawley rat and microdosimetric correlates.

Standard methods for risk assessments resulting from human exposures to mixed radiation fields in Space consisting of different particle types and energies rely upon quality factors. These are generally defined as a function of linear energy transfer (LET) and are assumed to be proportional to the risk. In this approach, it is further assumed that the risks for single exposures from each of the radiation types add linearly. Although risks of cancer from acute exposures to photon radiations have been measured in humans, quality factors for protons and ions of heavier atomic mass are generally inferred from animal and/or cellular data. Because only a small amount of data exists for such particles, this group has been examining tumourigenesis initiated by energetic protons and iron ions. In this study, 741 female Sprague-Dawley rats were irradiated or sham irradiated at approximately 60 days of age with 250 MeV protons, 1 GeV/nucleon iron ions or both protons and iron ions. The results suggest that the risk of mammary tumours in the rats sequentially irradiated with 1 GeV/nucleon 56Fe ions and 250 MeV protons is less than additive. These data in conjunction with earlier results further suggest that risk assessments in terms of only mean LETs of the primary cosmic rays may be insufficient to accurately evaluate the relative risks of each type of particle in a radiation field of mixed radiation qualities.

Animals↗

Psychiatric comorbidities in patients with Parkinson disease and psychosis.

OBJECTIVE: To determine the prevalence and impact of comorbid psychiatric disturbances in Parkinson disease (PD) patients with psychosis. METHODS: Subject data were derived from a research database of 116 PD patients participating in standardized motor, cognitive, psychiatric, and caregiver assessments. RESULTS: There were 25 patients (22%) with psychosis manifest as hallucinations (n = 9), delusions (n = 1), or hallucinations and delusions (n = 15) and 25 patients (22%) who had no current or past psychiatric comorbidities (PDN). In the psychotic group, 44% had psychosis only (PSY), and 56% had psychosis plus at least one other comorbid psychiatric disturbance (PSY+), including depressive disorders (71%), anxiety disorders (21%), apathetic syndromes (14%), and delirium (14%). There were no differences in age, sex, education, or age onset or duration of PD among the PSY, PSY+, and PDN groups. Both psychotic groups had greater motor, functional, and frontal cognitive deficits and increased caregiver burden scores relative to PDN. PSY+ showed greater global and selective cognitive deficits compared to PDN. Psychosis was a primary predictor of caregiver burden, whereas depressive symptoms indirectly enhanced motor impairments. CONCLUSIONS: Nonpsychotic psychiatric disturbances, especially affective disturbances, are common comorbidities in PD patients with psychosis and warrant clinical attention to reduce morbidity and caregiver distress.

Activities of Daily Living↗

Intracellular oxidation by human glioma cell populations: effect of arachidonic acid.

Arachidonic acid (AA) and Gamma linolenic acid have been shown to limit glioma cell growth, stimulate apoptosis and lipid peroxidation. However, brain tumours are characterised by cellular heterogeneity and responding cell populations have not been identified. Brain tumour samples from patients were disaggregated. In cell preparations from 7 gliomas, reactive oxygen species (ROS), morphology and plasma membrane integrity were monitored +/-18-36 microM AA for 15-120 min using flow cytometry. Basal oxidative activity related to cell size/morphology, small granular cells showed lower activity. AA stimulation of ROS formation depended on cell size/morphology. Large, less granular cells showed greater AA stimulation. In 17 gliomas, GFAP immunofluorescence was demonstrated in larger cell populations. The large GFAP positive cell population with low side scatter was the highest responding cell population, suggesting selective tumour cell sensitivity to AA induced ROS formation. ROS may have a role in AA induced cell death and anti-tumour activity of AA in glioma.

Antineoplastic Agents↗

Factors influencing atopic dermatitis-a questionnaire survey of schoolchildren's perceptions.

BACKGROUND: Although there is growing knowledge about factors that may predispose to the onset of atopic dermatitis (AD), little is known about factors which may exacerbate existing disease. AD sufferers and those involved in the management of the disease are often aware of factors that influence its course and severity. However, there is little available evidence on the distribution and relative importance of such factors, and what information exists is derived from selected groups such as hospital patients and may not therefore be representative of the AD population as a whole. OBJECTIVES: To determine the distribution and relative importance of 19 potential exacerbating and relieving factors as perceived by a population-based sample of schoolchildren with AD. METHODS: A questionnaire was used to identify all children with AD in years 8 and 9 (12-14-year-olds) from eight comprehensive schools across Wales. These individuals were then requested to complete a supplementary questionnaire which asked them to state for each of 19 factors whether (i) it makes their eczema better, (ii) it makes their eczema worse, (iii) it has no effect, or (iv) they do not know its effects. RESULTS: Almost 10% (250 of 2501) of children surveyed were considered to have AD, and 90% (225 of 250) of these completed the supplementary questionnaire. Most AD sufferers found that none to two factors relieve their symptoms whilst none to five factors exacerbate them. Sweating from exercise, fabrics (especially wool) and hot weather were the three most common exacerbators, affecting 41.8%, 40% and 39.1%, respectively, of AD responders. The three key relievers were steroid creams (22.2% of AD responders), moisturizers/makeup (16.4%) and medicines/tablets (13.8%). Almost 60% of respondents believed foods have no effect on their symptoms. There was also evidence to suggest that 12.4% (28 of 225) of participants may use creams which they are not aware contain steroids. CONCLUSIONS: These findings shed light on the relative perceived importance of factors such as food, aeroallergens, sweat, climate, illness, stress and therapies for the course of AD in a representative population sample of AD sufferers. Such information might be explored during clinical consultations given the increasing participation of sufferers and their carers in the management of this chronic disease. These findings also form the basis of hypothesis generation for future analytical studies.

Adolescent↗

Doctor-patient communication in a musculoskeletal unit: relationship between an observer-rated structured scoring system and patient opinion.

OBJECTIVES: To investigate the ability of consultant rheumatologists and orthopaedic surgeons to communicate well with patients and to determine the validity of a structured proforma used to assess medical students' communication skills. METHODS: Seventy new patient appointments with consultant rheumatologists and orthopaedic surgeons were assessed for communication skills exhibited by the consultants and patient satisfaction. Communication skills were assessed using a proforma previously used to examine medical students, and patient ratings were obtained using visual analogue scales. RESULTS: Median scores attained using the structured proforma for rheumatology, elective orthopaedic and fracture clinic consultations were 17, 15 and 14 out of 20 (P < 0.05). Patient satisfaction scores were high in all three domains measured. Scores were statistically significantly higher for rheumatology appointments than in fracture clinic (median scores 29.5, 29.5 and 28 out of 30). Consultation durations varied, with a median of 23 min for rheumatology and 10.5 and 4 min for orthopaedic surgeons in clinic and fracture clinic, respectively. CONCLUSIONS: Consultant rheumatologists and orthopaedic surgeons demonstrate good communication skills, according to a tool used to assess medical students. These scores correlate with patient views, suggesting that teaching and assessment of communication skills at medical schools may address concerns of patients. Scores and satisfaction correlate with the duration of the consultation.

Clinical Competence↗

Risk assessment of chromium and arsenic in date palm leaves used as livestock feed.

Appreciable levels of total chromium (Cr) and arsenic (As) were found (by emission spectroscopy) in date palm leaves, which form a significant ingredient in livestock feed. The levels in the fruit were considered safe for human consumption. Our work involved evaluation of the distribution of these elements in the leaves during the developmental stages of the fruiting season. Thirty-six leaf specimens of the Fard cultivar were collected 9, 15 and 20 weeks, respectively, after pollination and subjected to a standard digestion procedure. Sample masses of typically 1 g (dry weight) were prepared in 25 ml dilute acid solution and investigated for trace levels of Cr and As by ICP-AES. Eleven soil samples collected at random during the growth stages were subjected to a similar digestion procedure and analysis. According to the literature, the permissible mean levels of Cr and As in plants are 200 and 80 ng/g (dry weight), respectively. We used these values as our guideline to assess the "risk" levels in our samples of interest. In the case of Cr, about 45% of the specimens possessed levels between 250 and 700 ng/g, while a significant number produced levels between 1000 and 5000 ng/g. With regard to As, about 70% of the samples were above the documented permissible mean value. As a result of the unusually high Cr concentrations in some cases, the feasibility of Cr "accumulation" in the leaves was examined. Insects and other organisms subsist on the leaves and an added concern was the accumulation of these elements in the food chain. The study formed an interesting contribution to environmental research, and the impact of our assessment on the environment is discussed.

Animal Feed↗

Monitoring of cadmium in "on" and "off" date palms.

The study demonstrated that the mature dates we investigated were considered safe for human consumption. However, our findings revealed that much of the early fruit and leaves, which appeared at the advent of the fruiting season, possessed elevated levels of cadmium (Cd) that could accumulate in the food chain and thus impact adversely on the environment. In addition, animal feed for livestock contains date leaves, which should be restricted to the mature ones. The monitoring of cadmium in date palms is of considerable interest to environmental science and the thrust of this work, therefore, involved measurement, by ICP, of Cd in dates and corresponding leaf specimens, and evaluation of its distribution during the developmental stages of the fruiting season. Thirty-six date samples and 36 leaf specimens of the Fard cultivar were collected from "on" and "off" date palms during the Kimri, Bisir and Rutab stages of the fruiting season and subjected to suitable digestion procedures. Sample masses of typically 1 g (dry weight) were prepared in 25 ml dilute acid solution and investigated for trace levels of Cd by ICP-AES. Special attention was paid to contamination and the validation of our methodology. The Cd "threshold" in our study was 50 ng/g, in keeping with the levels of tolerance appearing in the literature. For the dates we found elevated levels of Cd [> 50 ng/g] in most of the samples, for both categories of "on" and "off" trees, during the Kimri stage. In the case of the leaves, the "on" samples revealed significant values up to 125 ng/g in Bisir, in some cases, but the trend for the "off" trees remained the same with the highest levels [> 100 ng/g] recorded during Kimri. Safe levels were attained during Rutab for all specimens. The possibility of a connection between Cd toxicity and the alternate-bearing phenomenon is discussed and this could be the subject of future interest.

Cadmium↗

Relative biological effectiveness of light ions in human tumoural cell lines: role of protein p53.

Protons and alpha particles of high linear energy transfer (LET) have shown an increased relative biological effectiveness (RBE) with respect to X/gamma rays for several cellular and molecular endpoints in different in vitro cell systems. To contribute to understanding the biochemical mechanisms involved in the increased effectiveness of high LET radiation, an extensive study has been designed. The present work reports the preliminary result of this study on two human tumoural cell lines, DLD1 and HCT116, (with different p53 status), which indicate that for these cell lines, p53 does not appear to take a part in the response to radiation induced DNA damage, suggesting an alternative p53-independent pathway and a cell biochemical mechanism dependent on the cell type.

Alpha Particles↗

IUdR polymers for combined continuous low-dose rate and high-dose rate sensitization of experimental human malignant gliomas.

Local polymeric delivery enhances IUdR radiosensitization of human malignant gliomas (MG). The combined low-dose rate (LDR) (0.03 Gy/h) and fractionated high-dose rate (HDR) treatments result in cures of experimental MGs. To enhance efficacy, we combined polymeric IUdR delivery, LDR, and HDR for treatments of both subcutaneous and intracranial MGs. In vitro: Cells (U251 MG) were trypsinized and replated in triplicate 1 day prior to LDR irradiation in media either without (control) or with 10 microM IUdR. After 72 hr, LDR irradiation cells were acutely irradiated (1.1 Gy/min) with increasing (0, 1.25, 2.5, 5.0, or 10 Gy) single doses. Implantable IUdR polymers [(poly(bis(p-carboxyphenoxy)-propane) (PCPP): sebaic acid (PCPP:SA), 20:80] (50% loading; 10 mg) were synthesized. In vivo: For flank vs. intracranial tumors, mice had 6 x 10(6) subcutaneous vs. 2 x 10(5) intracranial cells. For intracranial or subcutaneous MGs, mice had intratumoral blank (empty) vs. IUdR polymer treatments. One day after implantation, mice had immediate external LDR (3 cGy/h x 3 days total body irradiation) or HDR (2 Gy BID x 4 days to tumor site) or concurrent treatments. For the in vitro IUdR treatments, LDR resulted in a striking increase in cell-killing when combined with HDR. For the in vivo LDR treatments of flank tumors, the growth delay was greater for the IUdR vs. blank polymer treatments. For the combined LDR and HDR, the IUdR treatments resulted in a dramatic decrease in tumor volumes. On day 60 the log V/V0 were -1.7 +/- 0.22 for combined LDR + HDR + IUdR polymer (P < 0.05 vs. combined LDR + HDR + blank polymer). Survival for the intracranial controls was 22.9 +/- 1.2 days. For the blank polymer + LDR vs. blank polymer + LDR + HDR treatments, survival was 25.3 +/- 1.7 (P = NS) vs. 48.1 +/- 3.5 days (P < 0.05). For IUdR polymer + LDR treatment survival was 27.3 +/- 2.3 days (P = NS). The most striking improvement in survival followed the IUdR polymer + LDR + HDR treatment: 66.0 + 6.4 days (P < 0.05 vs. blank polymer + LDR + HDR). The polymeric IUdR delivery plus combined continuous LDR and HDR treatments results in growth delay and improved survival in animals bearing the MG xenografts. This treatment may hold promise for the treatment of human MGs.

Animals↗

Composition dependence of the nucleation energy of iron antimonides from modulated elemental reactants.

Modulated elemental reactants containing iron and antimony were found to react at low temperature (T < 200 degrees C) forming either FeSb(2) or FeSb(3) depending on both the layer thicknesses and the overall composition of the initial reactant. For films containing 75% antimony and 25% iron, the metastable compound FeSb(3) was observed to nucleate and grow if the layer thickness was below approximately 35 A. Above this critical thickness for the modulation, annealing led to the formation of FeSb(2). This, combined with low-angle diffraction data, suggests that the initial interdiffusion between iron and antimony layers in an elementally modulated reactant results in the formation of an amorphous reaction intermediate if the layering thickness is less than 35 A. For modulated reactants with composition between 70 and 90 atomic % antimony and below this critical layer thickness, the metastable compound FeSb(3) formed. In more iron-rich modulated reactants FeSb(2) nucleates. The nucleation temperature and the nucleation energy of FeSb(3) were found to be a function of the composition of the amorphous intermediate, while those of FeSb(2) were found to be relatively independent of composition.

Journal Article↗

Which primary shoulder and elbow replacement? A review of the results of prostheses available in the UK.

To assist surgeons select a suitable prosthesis, we have undertaken a detailed review of all shoulder and elbow replacements currently marketed in the UK. Twenty shoulder and 8 elbow implants, manufactured by 16 companies, have been identified. Twelve of the shoulder and one of the elbow implants have been introduced or modified in the last 8 years and have no clinical results published in peer-reviewed journals. Only the Biomodular, Bipolar, Copeland, Isoelastic, Neer hemi, Neer II, Roper-Day and Select shoulders accounting for less than 40% of the UK shoulder market, possess published results. The Capitello-condylar, Coonrad-Morrey, GSB III, Kudo, Liverpool, Roper-Tuke and Souter-Strathclyde elbows all have published results. These account for over 95% of all UK elbow replacements. The implications of these findings in an era of evidence-based medicine is discussed. Reviewing the clinical results should be of primary importance in the selection of a suitable prosthesis. Implants with a proven long-term record must represent the 'gold standard'. New or modified implants should only be used if they are part of a properly conducted clinical trial.

Arthroplasty, Replacement↗