Showing papers by "University of Salford published in 1999"

Patient survival after D-1 and D-2 resections for gastric cancer: long-term results of the MRC randomized surgical trial

Abstract: Controversy still exists on the optimal surgical resection for potentially curable gastric cancer. Much better long-term survival has been reported in retrospective/non-randomized studies with D2 resections that involve a radical extended regional lymphadenectomy than with the standard D1 resections. In this paper we report the long-term survival of patients entered into a randomized study, with follow-up to death or 3 years in 96% of patients and a median follow-up of 6.5 years. In this prospective trial D1 resection (removal of regional perigastric nodes) was compared with D2 resection (extended lymphadenectomy to include level 1 and 2 regional nodes). Central randomization followed a staging laparotomy. Out of 737 patients with histologically proven gastric adenocarcinoma registered, 337 patients were ineligible by staging laparotomy because of advanced disease and 400 were randomized. The 5-year survival rates were 35% for D1 resection and 33% for D2 resection (difference -2%, 95% CI = -12%-8%). There was no difference in the overall 5-year survival between the two arms (HR = 1.10, 95% CI 0.87-1.39, where HR > 1 implies a survival benefit to D1 surgery). Survival based on death from gastric cancer as the event was similar in the D1 and D2 groups (HR = 1.05, 95% CI 0.79-1.39) as was recurrence-free survival (HR = 1.03, 95% CI 0.82-1.29). In a multivariate analysis, clinical stages II and III, old age, male sex and removal of spleen and pancreas were independently associated with poor survival. These findings indicate that the classical Japanese D2 resection offers no survival advantage over D1 surgery. However, the possibility that D2 resection without pancreatico-splenectomy may be better than standard D1 resection cannot be dismissed by the results of this trial.

The cortical representation of pain.

Abstract: Anatomical and physiological studies in animals, as well as functional imaging studies in humans have shown that multiple cortical areas are activated by painful stimuli. The view that pain is perceived only as a result of thalamic processing has, therefore, been abandoned, and has been replaced by the question of what functions can be assigned to individual cortical areas. The following cortical areas have been shown to be involved in the processing of painful stimuli: primary somatosensory cortex, secondary somatosensory cortex and its vicinity in the parietal operculum, insula, anterior cingulate cortex and prefrontal cortex. These areas probably process different aspects of pain in parallel. Previous psychophysical research has emphasized the importance of separating pain experience into sensory-discriminative and affective-motivational components. The sensory-discriminative component of pain can be considered a sensory modality similar to vision or olfaction; it becomes more and more evident that it is subserved by its own apparatus up to the cortical level. The affective-motivational component is close to what may be considered 'suffering from pain'; it is clearly related to aspects of emotion, arousal and the programming of behaviour. This dichotomy, however, has turned out to be too simple to explain the functional significance of nociceptive cortical networks. Recent progress in imaging technology has, therefore, provided a new impetus to study the multiple dimensions of pain.

Case-based reasoning is a methodology not a technology

Abstract: This paper asks whether case-based reasoning is an artificial intelligence (AI) technology like rule-based reasoning, neural networks or genetic algorithms or whether it is better described as a methodology for problem solving, that may use any appropriate technology. By describing four applications of case-based reasoning (CBR), that variously use: nearest neighbour, induction, fuzzy logic and SQL, the author shows that CBR is a methodology and not a technology. The implications of this are discussed.

Topical Estrogen Accelerates Cutaneous Wound Healing in Aged Humans Associated with an Altered Inflammatory Response

Abstract: The effects of intrinsic aging on the cutaneous wound healing process are profound, and the resulting acute and chronic wound morbidity imposes a substantial burden on health services. We have investigated the effects of topical estrogen on cutaneous wound healing in healthy elderly men and women, and related these effects to the inflammatory response and local elastase levels, an enzyme known to be up-regulated in impaired wound healing states. Eighteen health status-defined females (mean age, 74.4 years) and eighteen males (mean age, 70.7 years) were randomized in a double-blind study to either active estrogen patch or identical placebo patch attached for 24 hours to the upper inner arm, through which two 4-mm punch biopsies were made. The wounds were excised at either day 7 or day 80 post-wounding. Compared to placebo, estrogen treatment increased the extent of wound healing in both males and females with a decrease in wound size at day 7, increased collagen levels at both days 7 and 80, and increased day 7 fibronectin levels. In addition, estrogen enhanced the strength of day 80 wounds. Estrogen treatment was associated with a decrease in wound elastase levels secondary to reduced neutrophil numbers, and decreased fibronectin degradation. In vitro studies using isolated human neutrophils indicate that one mechanism underlying the altered inflammatory response involves both a direct inhibition of neutrophil chemotaxis by estrogen and an altered expression of neutrophil adhesion molecules. These data demonstrate that delays in wound healing in the elderly can be significantly diminished by topical estrogen in both male and female subjects.

The Economics of Casino Gambling

Abstract: America's casino industry expanded rapidly in the 1990s, spreading from Nevada and Atlantic City to mining towns, riverboats, race tracks and tribal lands, and moving from isolated resort settings to urban and suburban venues. This article examines economic characteristics of the casino industry, including the evolution of major casino markets, pricing of gaming products, market structures, regulatory constraints, and social and economic impacts attributable to casinos. When competitive, casinos show strong economies of scale and scope, but many new jurisdictions limit the number or size of operations, thus creating substantial economic rents. Allocation of these rents are fundamentally politically determined.

A broadened conception of internal marketing

Abstract: Internal marketing has been of interest to practitioners and academics, in marketing and other disciplines of management, for some years, and published papers focus on definitions, the role of internal marketing in organisations, and various empirical investigations. Discusses the elements of a broadened concept on internal marketing, which emerges from: a systematic review and examination of the existing literature; case study material; “expert” opinion from leading academics; and interviews with managers.

Narrative in Virtual Environments - Towards Emergent Narrative

Abstract: In this paper we consider the clash between the pre-scripted character of much narrative and the freedom afforded by a Virtual Environment. We discuss the concept of emergent narrative as a possible way of avoiding this clash. We examine the role of a VE user in a narrative and consider the concept of social presence as a means of reconciling the freedom of the user with the constraints of an emergent narrative.

Factors affecting successful implementation of total productive maintenance

Abstract: Modern manufacturing requires that to be successful organisations must be supported by both effective and efficient maintenance. One approach to improving the performance of maintenance activities is to implement and develop a total productive maintenance (TPM) strategy. However, it is well documented that a number of organisations are failing to successfully implement such strategies. This paper outlines research carried out by the Aeronautical, Mechanical and Manufacturing Engineering Department at Salford University aimed at discovering the factors affecting the successful implementation of TPM. This research has led to the development of a generic model indicating factors affecting the successful implementation of TPM. The validity of the generic model has been tested in a UK manufacturing small‐ to medium‐size enterprise (SME) and the case study research findings further triangulated through a review of documented case study evidence. This research has also led to the development of recommendations to improve the TPM development and implementation program of the case study organisation. Further development of the research has resulted in a step‐wise program or generic roadmap for UK SMEs which is proposed as a tool for the implementation or rejuvenation of an organisation’s TPM program.

The impact of clinical, morphological, psychosocial and work-related factors on the outcome of lumbar discectomy

Abstract: In a prospective controlled trial on 46 patients undergoing lumbar discectomy, three classes of variables (medical data including MRI-identified morphological abnormalities, general psychological factors and psychosocial aspects of work) were analyzed with regard to their predictive value for the outcome of lumbar disc surgery at 2 year follow-up. Multiple regression analyses were used to identify the best predictor variables of four different outcome measures (i.e. pain relief, reduction of disability in daily activities, return to work and surgical outcome). MRI-identified nerve root compromise and social support from the spouse were independent predictors of pain relief 2 years after surgery (R2=0.40, P<0.01). Return to work 2 years after surgery was best predicted by depression and occupational mental stress (R2=0.36, P<0.001). MRI-identified extent of herniation and depression were significant predictors of a good surgical outcome after lumbar discectomy (R2=0.61, P<0.001). This study has demonstrated that the outcome of discectomy is critically dependent on which outcome variables are selected and that different sorts of predictor variables have a distinct influence on the various outcome variables. Obvious morphological alterations (i.e. disc extrusions, nerve root compromise) proved to be significant predictors of postoperative pain relief and improvement of disability in daily activities justifying a surgical treatment approach in these cases. The most important finding of this study was that return to work was not influenced by any clinical findings or MR-identified morphological alterations, but solely by psychological factors (i.e. depression) and psychological aspects of work (i.e. occupational mental stress).

Computer simulation of random packing of unequal particles.

Abstract: A Monte Carlo simulation model for the random packing of unequal spherical particles is presented in this paper. With this model, the particle radii obeying a given distribution are generated and randomly placed within a cubic packing domain with high packing density and many overlaps. Then a relaxation iteration is applied to reduce or eliminate the overlaps, while the packing space is gradually expanded. The simulation is completed once the mean overlap value falls below a preset value. To simulate the random close packing, a ``vibration'' process is applied after the relaxation iteration. For log-normal distributed particles, the effect of particle size standard deviation, and for bidisperse particles, the effects of particle size ratio and the volume fraction of large particles on packing density and on coordination number are investigated. Simulation results show good agreement with that obtained by experiments and by other simulations. The randomness, homogeneity, and isotropy, which have not been evaluated before for packing of distributed particles, are also examined using statistical measures.

Macroprolactinaemia : validation and application of the polyethylene glycol precipitation test and clinical characterization of the condition

Abstract: OBJECTIVE The clinical characteristics and natural history of macroprolactinaemia are yet to be fully established and there is currently no widely accepted simple in vitro test for routine identification of the condition. This study was designed to further validate the polyethylene glycol (PEG) precipitation test with assessment of percentage prolactin recovery (%R), for the detection of macroprolactinaemia and clinically characterize cases identified using the test. DESIGN Analytical validation and application of the PEG precipitation test for diagnosis of macroprolactinaemia and a retrospective case-notes review of some of the patients identified with the condition. PATIENTS Sera from 188 patients with elevated serum prolactin (PRL) concentrations were screened for macroprolactinaemia. Seventeen of the patients who were under follow-up at the local teaching hospital and were identified to have macroprolactinaemia were systematically characterized clinically. MEASUREMENTS Prolactin was measured in sera, fractions from gel filtration chromatography and supernatant obtained after PEG precipitation, by the DELFIA fluoroimmunoassay. CLINICAL ENDPOINTS Initial serum PRL and symptoms and their response to dopamine agonist therapy; imaging of the pituitary gland; serum PRL and symptoms after cessation of dopamine agonist therapy; course of serum PRL and symptoms without dopamine agonist therapy. RESULTS The within-batch coefficient of variation (CV) of the PEG precipitation test ranged between 2.8 and 7.3% while the between-batch CV ranged between 3.4 and 9.7%. Intra-individual variability up to five months was 9.9%. A prolactin recovery ≤ 40% was indicative of macroprolactinaemia, while the condition was unlikely to be present at values > 50%. The prevalence of macroprolactinaemia was 15% without sex difference. Clinical characterization of 17 patients showed modest initial serum PRL concentrations and there was imaging evidence of a coexisting pituitary adenoma in three of them. Dopamine agonist therapy resulted in substantial falls in serum PRL and this was associated with improvement or resolution of symptoms in some patients. Stoppage of dopamine agonist resulted in rebound hyperprolactinaemia in all cases. Spontaneous improvement in symptoms occurred in three patients but hyperprolactinaemia persisted in all those who were not on treatment. CONCLUSIONS The PEG precipitation test with assessment of ‘free’ prolactin has been shown to be reproducible and sensitive for the detection of macroprolactinaemia. Many of the patients who had macroprolactinaemia presented with at least one symptom of the hyperprolactinaemic syndrome. Dopaminergic therapy may influence the course of both serum PRL and symptoms in some of these patients.

Developments in delay time analysis for modelling plant maintenance

Abstract: Delay time (DT) analysis is a pragmatic mathematical concept readily embraced by engineers which has been developed as a means to model maintenance decision problems. Attention is focused upon the maintenance engineering decisions of what to do, as opposed to the logistical decisions of how to do it. This paper reviews the cumulative knowledge and experience of delay time modelling. The decision environment within which delay time (DT) models are intended as decision aids is briefly reviewed, and the initial development of simple DT models for a repairable component and a complex plant presented. Variations on the basic model are outlined and discussed including perfect and non-perfect inspection, steady state and non-steady state conditions, and homogeneous and non-homogeneous Poisson arrival rate of defects. Attention is given to the parameter estimation process, and both subjective and objective estimation techniques are outlined. Case sketches present practical experience in using the DT concept to model actual plant, to assess the benefits obtained, and to validate modelling and parameter assessment.

Recent advances in magnetron sputtering

Abstract: The paper will outline the historical development of sputtering techniques up to the recent development of closed-field unbalanced magnetron sputtering (CFUBMS). Examples will then be given of the use of CFUBMS to develop advanced coatings for industrial applications, including corrosion resistant coatings for aerospace, hard ceramic coatings for wear resistance, and coatings with novel thermal and chemical properties. Finally, current development in the technology and in understanding of the principles of the process will be described.

Nutrient losses in eroded sediment after fire in eucalyptus and pine forests in the wet Mediterranean environment of northern Portugal

Abstract: Nutrients sorbed onto eroded sediment from small bounded plots installed in newly burned and unburned Eucalyptus globulus and Pinus pinaster forests in the Agueda Basin, north-central Portugal were measured over an 18-month period. The data are used to determine: (i) the effects of fire on nutrient loss, (ii) the importance of fire-induced losses on soil fertility, and (iii) temporal variations in nutrient losses. Fire increased losses of total nitrogen, exchangeable potassium and available phosphorus by 3–4 orders of magnitude. This is attributed to increased erosion and high nutrient concentrations at the soil surface in the burned forests, where burning of organic matter and vegetation increased nutrient availability. Enhanced rates of loss were sustained for at least 3 years, resulting in much greater post-fire nutrient losses than reported in drier regions of the Mediterranean. Losses of available P had the greatest potential for reductions in soil fertility.

System dynamics applications to European health care issues

Abstract: Taking a European perspective, a review is made of some system dynamics models which address health care issues. Suggestions are made for the types of role which these models should take, bearing in mind the strategic orientation of system dynamics modelling. Examples are described of qualitative models where influence diagrams are the main analytical tool. Quantitative system dynamics models have a contribution to make in epidemiological studies and have been used to analyse the AIDS epidemic. A detailed example of one aspect of model formulation is given. This concerns the AIDS incubation time distribution and shows how real-world complications arising from virological staging and treatment effects are handled in a model of AIDS spread.

A journey to becoming: the student nurse in transition.

Abstract: The study reported in this paper explored the nature of the transition experienced by student nurses in their journey to becoming qualified nurses. In keeping with the developing relationship between the disciplines of anthropology and nursing, the methodology of choice was ethnography. Data were collected by open-ended questionnaires and interviews with key informants from one English College of Nursing undertaking Diploma level Project 2000 Adult Branch Studies. Thematic analysis of the data revealed an ill-defined transition for the student nurse and this lack of clarity was being perpetuated for many by their dual role as both student nurse and worker. This was also creating a potential role conflict and a blurring of the boundaries between professional nursing and skilled health care work. The data also revealed two 'in limbo' states, a ritualized transition phase, and that the rationale for 'learning to become a nurse' retains the idealized and vocational imagery of nursing as helping and caring for sick people.

History of Sleeping Sickness in East Africa

Abstract: The history of human sleeping sickness in East Africa is characterized by the appearance of disease epidemics interspersed by long periods of endemicity. Despite the presence of the tsetse fly in large areas of East Africa, these epidemics tend to occur multiply in specific regions or foci rather than spreading over vast areas. Many theories have been proposed to explain this phenomenon, but recent molecular approaches and detailed analyses of epidemics have highlighted the stability of human-infective trypanosome strains within these foci. The new molecular data, taken alongside the history and biology of human sleeping sickness, are beginning to highlight the important factors involved in the generation of epidemics. Specific, human-infective trypanosome strains may be associated with each focus, which, in the presence of the right conditions, can be responsible for the generation of an epidemic. Changes in agricultural practice, favoring the presence of tsetse flies, and the important contribution of domestic animals as a reservoir for the parasite are key factors in the maintenance of such epidemics. This review examines the contribution of molecular and genetic data to our understanding of the epidemiology and history of human sleeping sickness in East Africa.

Onchocerciasis modulates the immune response to mycobacterial antigens.

Abstract: Chronic helminth infection induces a type-2 cellular immune response. In contrast to this, mycobacterial infections commonly induce a type-1 immune response which is considered protective. Type-2 responses and diminished type-1 responses to mycobacteria have been previously correlated with active infection states such as pulmonary tuberculosis and lepromatous leprosy. The present study examines the immune responses of children exposed to both the helminth parasite Onchocerca volvulus and the mycobacterial infections, Mycobacterium tuberculosis and M. leprae. Proliferation of peripheral blood mononuclear cells (PBMC) and production of IL-4 in response to both helminth and mycobacterial antigen (PPD) decreased dramatically with increasing microfilarial (MF) density. Although interferon-gamma (IFN-gamma) production strongly correlated with cellular proliferation, it was surprisingly not related to MF density for either antigen. IL-4 production in response to helminth antigen and PPD increased with ascending children's age. IFN-gamma and cellular proliferation to PPD were not related to age, but in response to helminth antigen were significantly higher in children of age 9-12 years than children of either the younger age group (5-8 years) or the older group (13-16 years). Thus, there was a MF density-related down-regulation of cellular responsiveness and age-related skewing toward type 2 which was paralleled in response to both the helminth antigen and PPD. This parasite-induced immunomodulation of the response to mycobacteria correlates with a previous report of doubled incidence of lepromatous leprosy in onchocerciasis hyperendemic regions. Moreover, this demonstration that helminth infection in humans can modulate the immune response to a concurrent infection or immunological challenge is of critical importance to future vaccination strategies.

The role of spatial potential fluctuations in the shape of the PL bands of multinary semiconductor compounds

Abstract: Photoluminescence (PL) measurements of CuIn1-xGaxSe2 (x = 0.5) single crystals grown by the vertical Bridgmann technique were made at temperatures ranging from 11 K to 200 K and with various excitation powers. At low temperatures only one asymmetric PL band (BT-band) is present at 1.23 eV. It has a steeper decline on the high-energy side and nearly temperature independent low-energy side. At higher temperatures (T > 140 K) the BB-band becomes visible at 1.31 eV. We used an asymmetric double sigmoidal function to fit the experimental PL spectra. The results of this fitting can be interpreted to show the presence of spatial potential fluctuations in our samples. Observed dependencies would seem to reveal that the BT band is indeed connected with the recombination of a free electron with a localized hole. It is shown that these relatively deep localized states are probably formed due to potential fluctuations in highly compensated material and are not connected with any particular acceptor defect. We show that this model conforms to most of the discovered dependencies.

An integrated tactile/shear feedback array for stimulation of finger mechanoreceptor

Abstract: VR and telepresence applications have placed increasing demands on the need for effective user interfaces. To date most of the interfaces have emphasised the use of visual and audio effects but tactile feedback has been identified as a leading feature for future systems where there will be an increased desire to truly interact with the virtual/remote world rather than being observational. The paper focuses on the cutaneous aspects of tactile feedback describing the design and construction of pneumatically powered tactile and shear feedback modules. It is shown that by incorporating a range of novel features into this design it is possible to stimulate all the mechano-receptive nerves (SAI, SAII, RAI, and RAII) with localised signals from DC to 400 Hz. All this is shown in a fully integrated, ultra-light and comfortable package. The design control and performance results are all presented.

An extensive ultrasound and serologic study to investigate the prevalence of human cystic echinococcosis in northern Libya.

Abstract: A prevalence study of abdominal cystic echinococcosis (CE) was undertaken in the northwest, north-central, and northeast regions of Libya. A total of 36 villages along the coast were included, in which 20,220 people were screened by portable ultrasound. Three hundred thirty-nine (1.7%) were diagnosed with CE. There was no significant difference between CE prevalence rates in the three regions of Libya (mean = 1.6%); however, intervillage rates were variable, ranging from 0% to 4.5%. The prevalence of CE increased significantly with age (P < 0.0001) and females were significantly more affected (2%) than males (1.3%) (P < 0.0001). Cases of CE were distributed among 3.2% of housewives, 2.6% of farmers, 2.3% of male civil servants, 1.3% of female students, and 1.1% of male students. Housewives (P < 0.0001) and students (P < 0.0001) were significantly more at risk for CE. A statistically significant proportion (62% [210 of 339]) of CE cases kept dogs (P < 0.0001). Of the ultrasound-positive CE cases 69% (233 of 339) were antibody seropositive by ELISA using Echinococcus granulosus hydatid cyst fluid antigen B. Blood samples (n = 10,096) collected onto filter papers were taken randomly from ultrasound-negative people who entered the study, of which 11.2% were found to be seropositive. Seropositivity increased with age (P < 0.0001), with females exhibiting higher seroprevalence than males for all age groups (P < 0.0001). Seroprevalence was distributed occupationally among 17.3% of female students, 11.2% of male students, 8.3% of housewives, 7.3% of farmers, and 6.4% of male civil servants. Housewives and students were more likely to be seropositive (P < 0.0001). Forty-seven percent (526) of the seroreactors kept dogs. All liver hydatid cysts detected by ultrasound during community screening were classified according to morphology and size into six types. Type I (17.5% of all cases) were small univesicular cysts less than 50 mm in diameter with no laminations or daughter cysts. Type II (34%) were univesicular cysts with only laminations. Type IIIa (8.5%) were univesicular cysts with the appearance of laminations and daughter cysts. Type IIIb (13%) were univesicular with laminations and less prominent daughter cysts. Type IV (5.6%) presented as a solid mass. Type V were degenerated calcified or partially calcified cysts (13.2%). Type VI presented as multiple cysts (8% of all cases). The CE cases that exhibited Types II, IIIa, IIIb, IV or VI cysts showed the highest seropositivity (86%, 96%, 95%, 100%, and 96%, respectively), while Types I and V were the least seroreactive (38% and 22%, respectively). Cases of CE occurred in 311 families, with 93% having only one member as a CE case while 7% of the families had two or more cases. However, 25% of the ultrasound-negative persons belonging to families with an index CE case were seropositive for antibodies to Echinococcus. These results confirm the importance of human CE in Libya. They also confirm the usefulness of ultrasound combined with serology as a mass screening approach for CE in north African communities.

Sertraline in stroke-associated lability of mood

Abstract: Objective To assess whether a selective serotonin reuptake inhibitor is effective in the treatment of stroke-associated lability of mood. Methods Twenty-eight non-depressed patients suffering from post-stroke lability of mood took part in an 8-week double-blind randomized placebo-controlled trial of a selective serotonin reuptake inhibitor (50 mg sertraline per day). Results There were statistically significant improvements in a global rating of emotionalism and a specific benefit on tearfulness. The results are discussed in the light of proposed serontonergic mechanisms for emotional lability following stroke. Conclusions 50 mg of sertraline per day may be an effective and well-tolerated treatment for stroke-associated lability of mood in the absence of depression. This is supportive evidence for the serontonergic hypothesis of lability of mood following stroke. Copyright © 1999 John Wiley & Sons, Ltd.

Endothelial expression of nitric oxide synthases and nitrotyrosine in systemic sclerosis skin

Abstract: Although a multisystem disease, systemic sclerosis (SSc) most commonly affects the skin. The skin lesion is characterized by progressive changes, chief amongst which are vascular abnormalities, including endothelial cell (EC) injury and death, and dermal fibrosis. The pathogenesis of the vascular changes, and their relationship to dermal fibrosis, is poorly understood. The purpose of this study was to examine the potential role of nitric oxide (NO)-related free radical production, as part of an assessment of mechanisms leading to endothelial damage. Histologically graded skin biopsies from 33 patients with SSc (ten grade 0, ten grade 1, eight grade 2, and five grade 3) and eight healthy controls were reacted with antibodies against constitutive (eNOS) and inducible (iNOS) forms of nitric oxide synthase and nitrotyrosine. The degree of staining was assessed using a semi-quantitative system and a staining score was developed for the ECs of different vessel types in different areas of dermis at all grades. In biopsies from patients with SSc, superficial microvessel ECs showed a peak of eNOS expression in grade 1 skin which fell as the grade increased. By contrast, iNOS staining increased with the grade of skin lesion, a pattern paralleled by endothelial nitrotyrosine expression. From these findings, it is concluded that a metabolic switch occurs in dermal ECs from endothelial to cytokine inducible forms of NOS during the progression of the skin lesion of SSc. iNOS is a potent inducer of NO production which, in turn, can mediate NO free radical production. At a time of development of the SSc skin lesion when previous studies report evidence of EC damage, the cells express immunodetectable nitrotyrosine, a marker of NO-mediated free radical injury. The data suggest a role for iNOS-induced NO production in EC damage in SSc. Copyright 1999 John Wiley & Sons, Ltd.