Custom Law: Address to the New Zealand Society for Legal and Social Philosophy

The author was then the Chief Judge of the Māori Land Court and Chairperson of the Waitangi Tribunal. He is of Ngāti Kauwhata, Ngāti Raukawa and Rangitāne descent. The text is a paper delivered to the New Zealand Society for Legal and Social Philosophy at Victoria University of Wellington on 22 July 1994. The author introduces the laws of Māori to a non-Māori audience by providing a framework for a distinctive set of values that collectively constituted the Māori legal order. He begins with the constraints on the development of a custom law study. He then discusses the nature of customary law, noting that it reflects the social and political order of the people. The author also argues that a study of Māori land tenure was more than likely to reveal a substantial religious philosophy due to their long-standing personal connections to their land and whakapapa. The author concludes by lamenting the lack of a comprehensive study of Māori law as a science at the time.&nbsp

Background Paper

The Treaty of Waitangi Act 1975 constitutes the Waitangi Tribunal comprised of the Chief Judge of the Maori Land Court as chairperson and up to 16 additional members appointed by the Crown for terms not exceeding three years

Salmonella enterica biofilm-mediated dispersal by nitric oxide donors in association with cellulose nanocrystal hydrogels

Protected by extracellular polymers, microbes within biofilms are significantly more resistant to disinfectants. Current research has been instrumental in identifying nitric oxide donors and hydrogels as potential disinfectant additives. Nitric oxide (NO) donors are considered a very promising molecule as biofilm dispersal agents and hydrogels have recently attracted a lot of interest due to their biocompatible properties and ability to form stable thin films. When the NO donor MAHMA NONOate was dissolved in phosphate saline buffer, it was able to reduce the biomass of well-established biofilms up to 15% for at least 24 h of contact time. Encapsulation of MAHMA NONOate and molsidomine within a hydrogel composed of cellulose nanocrystals (CNC) has shown a synergistic effect in dispersing well-established biofilms: after 2 h of exposure, moderate but significant dispersion was measured. After 6 h of exposure, the number of cells transitioning from the biofilm to the planktonic state was up to 0.6 log higher when compared with non-treated biofilms. To further explore the transport processes of NO donors within hydrogels, we measured the nitric oxide flux from gels, at 25°C for a composite of 0.1 µM MAHMA NONOate–CNC. Nitric oxide diffuses up to 500 µm from the hydrogel surface, with flux decreasing according to Fick’s law. 60% of NO was released from the hydrogel composite during the first 23 min. These data suggest that the combined treatments with nitric oxide donor and hydrogels may allow for new sustainable cleaning strategies

Other Mechanical Methods for Pre-Induction Cervical Ripening.

Pre-induction cervical ripening is an important part of the labor induction process in women with an unfavorable cervix. This can be achieved either by pharmacologic or mechanical methods of cervical ripening. While the Foley catheter is the most commomly used mechanical method for labor induction, other mechanical methods are also available. This article reviews the safety profiles of osmotic dilators, extra-amniotic saline infusion, double-balloon catheters, and also compares their efficacy to that of other mechanical and pharmacologic cervical ripening methods. While mechanical methods have been shown to be safe and effective for cervical ripening, none of these alternatives has been shown to be superior to the Foley catheter

Voluntary versus ABC breath-hold in the context of VMAT for breast and locoregional lymph node radiotherapy including the internal mammary chain

Background: Deep-inspiration breath-hold (DIBH) reduces radiation dose to the heart in patients undergoing locoregional breast radiotherapy. In the context of tangential irradiation of the breast/ chest wall, a voluntary breath hold (vDIBH) technique has been shown to be as reproducible as a machine-assisted breath hold technique using the active breathing co-ordinator (ABCTM, Elekta, Crawley, UK, ABC_DIBH). This study compares set-up reproducibility for vDIBH versus ABC_DIBH in patients undergoing volumetric-modulated arc radiotherapy (VMAT) for breast cancer, both with and without wax bolus. Method: Patients with breast cancer requiring pan regional lymph node VMAT +/� wax bolus in breathhold were CT scanned in vDIBH and ABC_DIBH. Patients were randomised to receive one technique for fractions 1–7 and the other for fractions 8–15. Daily cone beam computed tomography (CBCT) was performed and registered to planning-CT using bony anatomy. Within-patient comparisons of mean daily chest wall position were made using a paired t-test. Population, systematic (P) and random errors (a) were estimated. Intrafraction reproducibility was assessed by comparing chest wall position and diaphragm movement between consecutive breath holds on CBCT. Results: 16 patients were recruited. All completed treatment with both techniques (9 patients with wax bolus, 7 patients without). CBCT derived P were 2.1–6.4 mm (ABC_DIBH) and 2.1–4.9 mm (vDIBH), a were 1.7–2.6 mm (ABC_DIBH) and 2.2–2.7 mm (vDIBH) and mean daily chest wall displacements (MD) were 0.0–1.5 mm (ABC_DIBH) and - 0.1–1.6 vDIBH (all p non-significant). Chest wall and diaphragm position was equivalent between consecutive breath holds in ABC and vDIBH (median difference 1.0 mm and 0.8 mm respectively, non p significant) demonstrating equivalent intrafraction reproducibility. Conclusion: This study demonstrates that a simple voluntary breath hold technique is feasible in combination with VMAT (+/� bolus) and is as reproducible as ABC_DIBH with VMAT for the irradiation of the breast and axillary and IMC lymph nodes in breast cancer patients

Molecular consequences of cystic fibrosis transmembrane regulator (CFTR) gene mutations in the exocrine pancreas

Background and aims: We tested the hypothesis that the actual or predicted consequences of mutations in the cystic fibrosis transmembrane regulator gene correlate with the pancreatic phenotype and with measures of quantitative exocrine pancreatic function. Methods: We assessed 742 patients with cystic fibrosis for whom genotype and clinical data were available. At diagnosis, 610 were pancreatic insufficient, 110 were pancreatic sufficient, and 22 pancreatic sufficient patients progressed to pancreatic insufficiency after diagnosis. Results: We identified mutations on both alleles in 633 patients (85.3%), on one allele in 95 (12.8%), and on neither allele in 14 (1.9%). Seventy six different mutations were identified. The most common mutation was ΔF508 (71.3%) followed by G551D (2.9%), G542X (2.3%), 621+1G→T (1.2%), and W1282X (1.2%). Patients were categorized into five classes according to the predicted functional consequences of each mutation. Over 95% of patients with severe class I, II, and III mutations were pancreatic insufficient or progressed to pancreatic insufficiency. In contrast, patients with mild class IV and V mutations were consistently pancreatic sufficient. In all but four cases each genotype correlated exclusively with the pancreatic phenotype. Quantitative data of acinar and ductular secretion were available in 93 patients. Patients with mutations belonging to classes I, II, and III had greatly reduced acinar and ductular function compared with those with class IV or V mutations. Conclusion: The predicted or known functional consequences of specific mutant alleles correlate with the severity of pancreatic disease in cystic fibrosis.published_or_final_versio

Analysis of Lymphocyfic Infiltration in Uveal Melanoma

Among 27 uveal melanomas, five were found to contain tumor infiltrating lymphocytes (TILs). Four had high levels of lymphocytes, and the fifth had comparatively low levels but adequate numbers for comprehensive analysis. The TILs were analyzed by flow cytometry to determine the relative proportions of lymphocyte subsets and markers of lymphocyte activation. The results show the predominance of T-suppressor/cytotoxic lymphocytes and insignificant levels of B-cells present in the infiltrate. The T-suppressor/cytotoxic cells were generally activated to a higher degree than the T-helper cells when assayed for levels of the histocompatibility antigen, HLA-DR. T-helper cells expressed more interleukin (IL-2) receptor (Tac) than T-suppressor/cytotoxic cells. Invest Ophthalmol Vis Sci 31: [2106][2107][2108][2109][2110]1990 Uveal melanomas, like their cutaneous counterpart, are considered to be relatively susceptible to immunologic influences because of reports of spontaneous regression, 1 -2 of the development of vitiligo and halo nevi, 5 Such intraocular transplantation can be prevented by prior adoptive transfer of humoral or cellular immunity to the recipient. " 14 Some investigators report the predominance of the T-cytotoxic/suppressor cell subpopulation; 1213 others found a majority of T-helper/inducer cells. 10 " 14 There is, however, no convincing evidence that a more favorable prognosis is associated with lymphocytic infiltration in uveal melanomas, 715 and it remains uncertain whether tumor infiltrating lymphocytes (TILs) play a significant role in tumor immunity. The availability of precisely defined monoclonal-antibody markers and flow-cytometric techniques makes it From the *Department of Biochemistry and the fTennent Institute of Ophthalmology, University of Glasgow, Glasgow, Scotland. Reprint requests: Fiona H. Durie, Department of Biochemistry, University of Glasgow, Glasgow G12 8QQ, UK. possible to do a detailed objective analysis of a large number of lymphocytes in any tumour. We characterized the phenotype of the TILs and studied the expression of the histocompatibility antigen, HLA-DR, and interleukin (IL-2) receptor (Tac), which are markers of activation, on the surface of T-helper and T-suppressor/cytotoxic lymphocytes in ocular melanoma. Materials and Methods Preparation of Cells Tissue was obtained from five choroidal melanomas which were removed either by local resection or by enucleation. Slices were cut from the apical part of the fresh specimen after preliminary examination, and these were transferred to RPMI-1640 medium (Gibco, Grand Island, NY). Spilled cells were teased out using a sterile needle. The cells were then harvested, washed by centrifugation at 1000 rpm for 15 min, counted, and adjusted to 1X10 6 cells/ml. The remaining cell suspensions of TILs and tumor cells were cryopreserved in medium containing 90% fetal calf serum and 10% dimethylsulfoxide and stored in liquid nitrogen until use. Four of the five patients consented to venipuncture, and peripheral blood lymphocytes were separated on a discontinuous ficoll density gradient. 1617 Preparation of Samples Cell suspensions of TILs and tumor cells were washed and resuspended in 1 ml of phosphate-buffered saline. Cells (50 ii\) were incubated on ice with appropriate fluorescein isothiocyanate (FITC)-conjugated leu series monoclonal antibody and phycoerythrin (PE) conjugated antibody (Becton-Dickinson, 2106 Downloaded from iovs.arvojournals.org on 06/28/201

Increased apoptosis of immunoreactive host cells and augmented donor leukocyte chimerism, not sustained inhibition of B7 molecule expression are associated with prolonged cardiac allograft survival in mice preconditioned with immature donor dendritic cells plus anti-CD40L mAb

Background. We previously reported the association among donor leukocyte chimerism, apoptosis of presumedly IL-2-deficient graft-infiltrating host cells, and the spontaneous donor-specific tolerance induced by liver but not heart allografts in mice. Survival of the rejection-prone heart allografts in the same strain combination is modestly prolonged by the pretransplant infusion of immature, costimulatory molecule-(CM) deficient donor dendritic cells (DC), an effect that is markedly potentiated by concomitant CM blockade with anti-CD40L (CD154) monoclonal antibody (mAb). We investigated whether the long survival of the heart allografts in the pretreated mice was associated with donor leukocyte chimerism and apoptosis of graft-infiltrating cells, if these end points were similar to those in the spontaneously tolerant liver transplant model, and whether the pretreatment effect was dependent on sustained inhibition of CM expression of the infused immature donor DC. In addition, apoptosis was assessed in the host spleen and lymph nodes, a critical determination not reported in previous studies of either spontaneous or 'treatment-aided' organ tolerance models. Methods. Seven days before transplantation of hearts from B10 (H-2b) donors, 2 x 106 donor- derived immature DC were infused i.v. into C3H (H-2(k)) recipient mice with or without a concomitant i.p. injection of anti-CD40L mAb. Donor cells were detected posttransplantation by immunohistochemical staining for major histocompatibility complex class II (I-Ab) in the cells of recipient lymphoid tissue. CM expression was determined by two-color labeling. Host responses to donor alloantigen were quantified by mixed leukocyte reaction, and cytotoxic T lymphocyte (CTL) assays. Apoptotic death in graft- infiltrating cells and in areas of T-dependent lymphoid tissue was visualized by terminal deoxynucleotidyltransferase-catalyzed dUTP-digoxigenin nick-end labeling and quantitative spectrofluorometry. Interleukin-2 production and localization were estimated by immunohistochemistry. Results. Compared with control heart transplantation or heart transplantation after only DC administration, concomitant pretreatment with immature donor DC and anti- CD40L mAb caused sustained elevation of donor (I-Ab+) cells (microchimerism) in the spleen including T cell areas. More than 80% of the I-Ab+ cells in combined treatment animals also were CD86+, reflecting failure of the mAb to inhibit CD40/CD80/CD86 up-regulation on immature DC in vitro after their interaction with host T cells. Donor-specific CTL activity in graft-infiltrating cells and spleen cell populations of these animals was present on day 8, but decreased strikingly to normal control levels by day 14. The decrease was associated with enhanced apoptosis of graft-infiltrating cells and of cells in the spleen where interleukin-2 production was inhibited. The highest levels of splenic microchimerism were found in mice with long surviving grafts (> 100 days). In contrast, CTL activity was persistently elevated in control heart graft recipients with comparatively low levels of apoptotic activity and high levels of interleukin-2. Conclusion. The donor-specific acceptance of rejection-prone heart allografts by recipients pretreated with immature donor DC and anti-CD40L mAb is not dependent on sustained inhibition of donor DC CM (CD86) expression. Instead, the pretreatment facilitates a tolerogenic cascade similar to that in spontaneously tolerant liver recipients that involves: (1) chimerism-driven immune activation, succeeded by deletion of host immune responder cells by apoptosis in the spleen and allograft that is linked to interleukin-2 deficiency in both locations and (2) persistence of comparatively large numbers of donor-derived leukocytes. These tolerogenic mechanisms are thought to be generic, explaining the tolerance induced by allografts spontaneously, or with the aid of various kinds of immunosuppression

Role of radiography, MRI and FDG-PET/CT in diagnosing, staging and therapeutical evaluation of patients with multiple myeloma

Multiple myeloma is a malignant B-cell neoplasm that involves the skeleton in approximately 80% of the patients. With an average age of 60 years and a 5-years survival of nearly 45% Brenner et al. (Blood 111:2516–2520, 35) the onset is to be classified as occurring still early in life while the disease can be very aggressive and debilitating. In the last decades, several new imaging techniques were introduced. The aim of this review is to compare the different techniques such as radiographic survey, multidetector computed tomography (MDCT), whole-body magnetic resonance imaging (WB-MRI), fluorodeoxyglucose positron emission tomography- (FDG-PET) with or without computed tomography (CT), and 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy. We conclude that both FDG-PET in combination with low-dose CT and whole-body MRI are more sensitive than skeleton X-ray in screening and diagnosing multiple myeloma. WB-MRI allows assessment of bone marrow involvement but cannot detect bone destruction, which might result in overstaging. Moreover, WB-MRI is less suitable in assessing response to therapy than FDG-PET. The combination of PET with low-dose CT can replace the golden standard, conventional skeletal survey. In the clinical practise, this will result in upstaging, due to the higher sensitivity