Fairness in Ancillary Relief

This article stems from setting student projects. It describes in detail the outcome of a project designed to ascertain the views of the public in relation to ancillary relief and what they consider to be a 'fair' outcome. The rationale for undertaking student projects has been discussed at length in another article and is therefore only alluded to here. The discussion centres around the law, findings and outcome of the project. Students studying the Family Law course at Sheffield University were required to survey members of the public in order to gather their views on the division of assets on divorce and then to analyse the public's response in light of the seminal decision of the House of Lords in White v White [2001] 1 AC 596.

PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma

Summary Bortezomib (formerly PS-341) has significant activity in patients with relapsed multiple myeloma (MM), its efficacy is increased with the addition of dexamethasone and it demonstrates synergy with doxorubicin, thus providing the rationale for combination therapy with bortezomib, doxorubicin and dexamethasone (PAD). Patients with untreated MM received four 21-d cycles of PAD, comprising bortezomib 1·3 mg/m2 on days 1, 4, 8 and 11, along with dexamethasone 40 mg on days 1–4, 8–11 and 15–18 during cycle 1 and days 1–4 during cycles 2–4. During days 1–4, patients also received 0, 4·5 or 9 mg/m2 of doxorubicin at dose levels 1, 2, and 3 respectively. Following peripheral blood stem cell (PBSC) collection, patients received high-dose melphalan (MEL200) with PBSC transplantation (PBSCT). After PAD induction alone, 20 of 21 patients (95%) achieved at least a partial response (PR), including complete response (CR) in five patients (24%). Twenty of 21 had PBSC mobilized, and 18 of 20 received MEL200/PBSCT. In an intention-to-treat analysis, response rates were: CR 43%, near CR 14%, very good PR 24%, PR 14% and stable disease 5%. PAD was effective, did not prejudice subsequent PBSC collection, and should be further evaluated in prospective randomized trials.

UKCP: A Collaborative network of cerebral palsy registers in the United Kingdom

Cerebral palsy (CP) is a relatively rare condition with enormous social and financial impact. Information about CP is not routinely collected in the United Kingdom. We have pooled non-identifiable data from the five currently active UK CP registers to form the UKCP database: birth years 1960–1997. This article describes the rationale behind this collaboration and the creation of the database. Data about 6910 children with CP are currently held. The mean annual prevalence rate was 2.0 per 1000 live births for birth years 1986–1996. Where type is known, 91 per cent have spastic CP. Where data are available, nearly one-third of children have severely impaired lower limb function, and nearly a quarter have severely impaired upper limb function. As well as describing the range and complexity of motor and associated impairments, the pooled data from the UKCP database provide a platform for studies of aetiology, long-term outcomes, participation and service needs. The UKCP database is an important national resource for the surveillance of CP and the study of its epidemiology in the United Kingdom.

The PD-1/PD-L1 Axis: An Immune-Mediated Mechanism of Chemoresistance in Cancer

The ability of tumour cells to avoid immune destruction (immune escape) and their acquired resistance to anti-cancer drugs constitute important barriers to the successful management of cancer. The interaction between specific molecules on the surface of tumour cells with their corresponding receptors on immune effector cells can result in inhibition of these effector cells, consequently allowing tumour cells to evade the host’s anti-tumour immune response. The interaction of the Programmed Death Ligand 1 (PD-L1) on the surface of tumour cells with the Programmed Death-1 (PD-1) receptor on cytotoxic T lymphocytes leads to inactivation of these immune effectors, and is a specific example of an immune escape mechanism tumour cells use to avoid immune destruction. Clinically, antibodies capable of blocking the PD-1/PD-L1 interaction have demonstrated significant therapeutic benefit, and are currently being used to help bolster patients’ immune response against malignant cells in a variety of cancer types. Here we show that the PD-1/PD-L1 interaction also leads to tumour cell resistance to conventional chemotherapeutic agents. Incubation of PD-L1-expressing human and mouse tumour cells with PD-1-expressing Jurkat T cells or purified recombinant PD-1 resulted in tumour cell resistance to doxorubicin and docetaxel. Interference with the PD-1/PD-L1 interaction using blocking anti-PD-1 or anti-PD-L1 antibody or shRNA-mediated gene silencing resulted in attenuation of PD-1/PD-L1-mediated drug resistance. Moreover, inhibition of the PD-1/PD-L1 signalling axis using anti-PD-1 antibody enhanced the effect of doxorubicin chemotherapy to inhibit 4T1 tumour cell metastasis in an in vivo mouse model of mammary carcinoma. These findings indicate that blockade of the PD-1/PD-L1 axis may be a useful approach to immunosensitize and chemosensitize tumours in cancer patients and provide a rationale for the use of anti-PD-1/PD-L1 antibodies as adjuvants to chemotherapy.

Detection of Anaerobic Bacteria in High Numbers in Sputum from Patients with Cystic Fibrosis

Rationale: Pulmonary infection in cystic ?brosis (CF) is polymicrobial and it is possible that anaerobic bacteria, not detected by routine aerobic culture methods, reside within infected anaerobic airway
mucus.
Objectives: To determine whether anaerobic bacteria are present in the sputum of patients with CF.
Methods: Sputum samples were collected from clinically stable adults with CF and bronchoalveolar lavage ?uid (BALF) samples from children with CF. Induced sputum samples were collected from healthy volunteers who did not have CF. All samples were processed using anaerobic bacteriologic techniques and bacteria within the samples were quanti?ed and identi?ed.
Measurements and Main Results: Anaerobic species primarily within the genera Prevotella,Veillonella, Propionibacterium, andActinomyces were isolated in high numbers from 42 of 66 (64%) sputum samples from adult patients with CF. Colonization with Pseudomonas aeruginosa signi?cantly increased the likelihood that anaerobic bacteria would be present in the sputum. Similar anaerobic species were identi?ed in BALF from pediatric patients with CF. Although anaerobes were detected in induced sputum samples from 16 of 20 volunteers, they were present in much lower numbers and were
generally different species compared with those detected in CF sputum. Species-dependent differences in the susceptibility of the anaerobes to antibiotics with known activity against anaerobes were apparent with all isolates susceptible to meropenem.
Conclusions: A range of anaerobic species are present in large numbers in the lungs of patients with CF. If these anaerobic bacteria are contributing signi?cantly to infection and in?ammation in the CF
lung, informed alterations to antibiotic treatment to target anaerobes, in addition to the primary infecting pathogens, may improve management.

Pathophysiology of anemia and erythrocytosis.

An increasing understanding of the process of erythropoiesis raises some interesting questions about the pathophysiology, diagnosis and treatment of anemia and erythrocytosis. The mechanisms underlying the development of many of the erythrocytoses, previously characterised as idiopathic, have been elucidated leading to an increased understanding of oxygen homeostasis. Characterisation of anemia and erythrocytosis in relation to serum erythropoietin levels can be a useful addition to clinical diagnostic criteria and provide a rationale for treatment with erythropoiesis stimulating agents (ESAs). Recombinant human erythropoietin as well as other ESAs are now widely used to treat anemias associated with a range of conditions, including chronic kidney disease, chronic inflammatory disorders and cancer. There is also heightened awareness of the potential abuse of ESAs to boost athletic performance in competitive sport. The discovery of erythropoietin receptors outside of the erythropoietic compartment may herald future applications for ESAs in the management of neurological and cardiac diseases. The current controversy concerning optimal hemoglobin levels in chronic kidney disease patients treated with ESAs and the potential negative clinical outcomes of ESA treatment in cancer reinforces the need for cautious evaluation of the pleiotropic effects of ESAs in non-erythroid tissues.

The L Pack: Addressing the Sexual Health Needs of Young Lesbians

Concerns about the sexual health of women who identify as other than heterosexual have been highlighted in numerous research reports, yet access to information, advice and services remains limited within Northern Ireland. In response to this, a group of young women have produced a sexual health resource (‘‘The L Pack’’) specifically for those who identify as lesbian or bisexual. This article discusses the issue of lesbian sexual health and the rationale for the production of The L Pack. Drawing upon discussions with the young women involved and the various partners, it outlines the participatory process of producing information for young women by young women, the meaning and value of this and the nature of learning for all involved. Illustrating feminist and related principles through practice examples, the article outlines how the project moved from a focus on individual learning to one where the young women involved gained the knowledge, skills and confidence to take their learning to their peers and others.

Dipeptidyl peptidase IV (DPP IV) and related molecules in type 2 diabetes

Dipeptidyl peptidase IV (DPP IV) is a widely distributed physiological enzyme that can be found solubilized in blood, or membrane-anchored in tissues. DPP IV and related dipeptidase enzymes cleave a wide range of physiological peptides and have been associated with several disease processes including Crohn's disease, chronic liver disease, osteoporosis, multiple sclerosis, eating disorders, rheumatoid arthritis, cancer, and of direct relevance to this review, type 2 diabetes. Here, we place particular emphasis on two peptide substrates of DPP IV with insulin-releasing and antidiabetic actions namely, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The rationale for inhibiting DPP IV activity in type 2 diabetes is that it decreases peptide cleavage and thereby enhances endogenous incretin hormone activity. A multitude of novel DPP IV inhibitor compounds have now been developed and tested. Here we examine the information available on DPP IV and related enzymes, review recent preclinical and clinical data for DPP IV inhibitors, and assess their clinical significance.

The prevalence of nonadherence in difficult asthma

Rationale: With the advent of new and expensive therapies for severe refractory asthma, targeting the appropriate patients is important. An important issue is identifying nonadherence with current therapies. The extent of nonadherence in a population with difficult asthma has not been previously reported.

Objectives: To examine the prevalence of nonadherence to corticosteroid medication in a population with difficult asthma referred to a Specialist Clinic and to examine the relationship of poor adherence to asthma outcome.

Methods: General practitioner prescription refill records for the previous 6 months for inhaled combination therapy and short-acting ß-agonists were compared with initial prescriptions and expressed as a percentage. Blood plasma prednisolone and cortisol assay levels were used to examine the utility of these measures in assessing adherence to oral prednisolone. Patient demographics, hospital admissions, lung function, oral prednisolone courses, and quality of life data were analyzed to indentify the variables associated with reduced medication adherence.

Measurements and Main Results: A total of 182 patients were assessed. Sixty-three patients (35%) filled 50% or fewer inhaled medication prescriptions; 88% admitted poor adherence with inhaled therapy after initial denial. Twenty-one percent of patients filled more than 100% of presciptions, and 45% of subjects filled between 51 and 100% of prescriptions. Twenty-three of 51 patients (45%) prescribed oral steroids were found to be nonadherent.

Conclusions: A significant proportion of patients with difficult-to-control asthma remained nonadherent to corticosteroid therapy. Objective surrogate and direct measures of adherence should be performed as part of a difficult asthma assessment and are important before prescibing expensive novel biological therapies.

British drugs policy: Problematizing the distinction between legal and illegal drugs and the definition of the ‘drugs problem’.

This article draws upon an extensive literature review of the social and medical sciences, official documents and various websites to critically re-evaluate the basis of British drugs policy. The article problematizes the rationale for criminalizing certain substances and questions the distinctions created between legal and illegal drugs; in so doing, the article argues that the definition of the `drugs problem' is the real problem. It shows that the debate on illegal drugs is filled less with factual truths and more with misinformation which creates public fear and provides a questionable basis for public policy. The article questions current thinking regarding the drugs/crime relationship and concludes by exploring some implications for policy and practice.

Working with a child Exposed to Community and Domestic violence in Northern Ireland: An Illustrated Case Example.

The focus of this paper is on the author’s multi-modal therapeutic practice with a 7-year-old boy referred to the Family Trauma Centre, following paramilitary assaults on his father. The work also addresses the boy’s experience of domestic violence. The work is contextualised in terms of the ‘Peace Process’ in Northern Ireland, including the establishment of the Family Trauma Centre as a response to the needs of victims of the Troubles. A rationale for working with children using a multi-modal approach is presented.

‘Doing it with men’: feminist research practice and patriarchal inheritance practices in Welsh family farming

Internationally, the gender relations of the family farming ‘way of life’ have beenshown to be stubbornly persistent in their adherence to patriarchal inheritancepractices. This article demonstrates how such ‘agri-cultural’ practices are situated bothwithin the subjective sphere of farming individuals’ and within global agri-economics,bringing new challenges to patrilineal farm survival. It is suggested here that the recenttendency for post-structuralist theorisation in rural studies has underestimated theexistence and impact of patrilineal patterns in family farming. Such patterns mean thatwomen are shown to largely occupy relational gender identities as the ‘helper’, whilstmen are strongly identified as the ‘farmer’. Drawing on repeated life-history interviewsconducted with farming men and women from Powys, Mid Wales, the aim of thisarticle is to generate debate as to the extent to which men can be brought into feministresearch practice in order to reveal patriarchy to a greater degree. The article begins bysituating the near-exclusion of men from feminist research practice within theoreticaldevelopments in feminist geography. This discussion also assists in deriving issues ofresearch methods, positionality and interpretive power which focus the integration ofempirical material in the methodological reflections provided in section three. In sectiontwo, the rationale for the epistemological stance taken in the research is provided. Thearticle provides an example of the successful integration of men into a feminist researchframe, suggests avenues for theoretical development and identifies future researchdirections which can be informed by ‘doing it with men’.

Keywords: epistemology; family farming; feminist res

Simvastatin Decreases Lipopolysaccharide-induced Pulmonary Inflammation in Healthy Volunteers

RATIONALE:
Simvastatin inhibits inflammatory responses in vitro and in murine models of lung inflammation in vivo. As simvastatin modulates a number of the underlying processes described in acute lung injury (ALI), it may be a potential therapeutic option.
OBJECTIVES:
To investigate in vivo if simvastatin modulates mechanisms important in the development of ALI in a model of acute lung inflammation induced by inhalation of lipopolysaccharide (LPS) in healthy human volunteers.
METHODS:
Thirty healthy subjects were enrolled in a double-blind, placebo-controlled study. Subjects were randomized to receive 40 mg or 80 mg of simvastatin or placebo (n = 10/group) for 4 days before inhalation of 50 microg LPS. Measurements were performed in bronchoalveolar lavage fluid (BALF) obtained at 6 hours and plasma obtained at 24 hours after LPS challenge. Nuclear translocation of nuclear factor-kappaB (NF-kappaB) was measured in monocyte-derived macrophages.
MEASUREMENTS AND MAIN RESULTS:
Pretreatment with simvastatin reduced LPS-induced BALF neutrophilia, myeloperoxidase, tumor necrosis factor-alpha, matrix metalloproteinases 7, 8, and 9, and C-reactive protein (CRP) as well as plasma CRP (all P < 0.05 vs. placebo). There was no significant difference between simvastatin 40 mg and 80 mg. BALF from subjects post-LPS inhalation induced a threefold up-regulation in nuclear NF-kappaB in monocyte-derived macrophages (P < 0.001); pretreatment with simvastatin reduced this by 35% (P < 0.001).
CONCLUSIONS:
Simvastatin has antiinflammatory effects in the pulmonary and systemic compartment in humans exposed to inhaled LPS.

Analytical Elastic Stiffness Model for 3D Woven Orthogonal Interlock Composites

This research presents the development of an analytical model to predict the elastic stiffness performance of orthogonal interlock bound 3D woven composites as a consequence of altering the weaving parameters and constituent material types. The present approach formulates expressions at the micro level with the aim of calculating more representative volume fractions of a group of elements to the layer. The rationale in representing the volume fractions within the unit cell more accurately was to improve the elastic stiffness predictions compared to existing analytical modelling approaches. The models developed in this work show good agreement between experimental data and improvement on existing predicted values by models published in literature.

An exploration of knowledge and attitudes related to pre-pregnancy care in women with diabetes

Aims: Pre-pregnancy care optimizes pregnancy outcome in women with pre-gestational diabetes, yet most women enter pregnancy unprepared. We sought to determine knowledge and attitudes of women with Type 1 and Type 2 diabetes of childbearing age towards pre-pregnancy care.

Methods: Twenty-four women (18 with Type 1 diabetes and six with Type 2 diabetes) aged 17–40 years took part in one of four focus group sessions: young nulliparous women with Type 1 diabetes (Group A), older nulliparous women with Type 1 diabetes (Group B), parous women with Type 1 diabetes (Group C) and women with Type 2 diabetes of mixed parity (Group D).

Results: Content analysis of transcribed focus groups revealed that, while women were well informed about the need to plan pregnancy, awareness of the rationale for planning was only evident in parous women or those who had actively sought pre-pregnancy advice. Within each group, there was uncertainty about what pre-pregnancy advice entailed. Despite many women reporting positive healthcare experiences, frequently cited barriers to discussing issues around family planning included unsupportive staff, busy clinics and perceived social stereotypes held by health professionals.

Conclusions: Knowledge and attitudes reported in this study highlight the need for women with diabetes, regardless of age, marital status or type of diabetes, to receive guidance about planning pregnancy in a motivating, positive and supportive manner. The important patient viewpoints expressed in this study may help health professionals determine how best to encourage women to avail of pre-pregnancy care