Nature of the Spin Liquid Ground State in a Breathing Kagome Compound Studied by NMR and Series Expansion.

In the vanadium oxyfluoride compound (NH_{4})_{2}[C_{7}H_{14}N][V_{7}O_{6}F_{18}] (DQVOF), the V^{4+} (3d^{1}, S=1/2) ions realize a unique, highly frustrated breathing kagome lattice composed of alternately sized, corner-sharing equilateral triangles. Here we present an ^{17}O NMR study of DQVOF, which isolates the local susceptibility of the breathing kagome network. By a fit to series expansion, we extract the ratio of the interactions within the breathing kagome plane, J_{∇}/J_{Δ}=0.55(4), and the mean antiferromagnetic interaction J[over ¯]=60(7) K. Spin lattice (T_{1}) measurements reveal an essentially gapless excitation spectrum with a maximum gap Δ/J[over ¯]=0.007(7). Our study provides new impetus for further theoretical investigations in order to establish whether the gapless spin liquid behavior displayed by DQVOF is intrinsic to its breathing kagome lattice or whether it is due to perturbations to this model, such as a residual coupling of the V^{4+} ions in the breathing kagome planes to the interlayer V^{3+} (S=1) spins.

Structural analysis of IPC zeolites and related materials using positron annihilation spectroscopy and high-resolution argon adsorption.

The advanced investigation of pore networks in isoreticular zeolites and mesoporous materials related to the IPC family was performed using high-resolution argon adsorption experiments coupled with the development of a state-of-the-art non-local density functional theory approach. The optimization of a kernel for model sorption isotherms for materials possessing the same layer structure, differing only in the interlayer connectivity (e.g. oxygen bridges, single- or double-four-ring building units, mesoscale pillars etc.) revealed remarkable differences in their porous systems. Using high-resolution adsorption data, the bimodal pore size distribution consistent with crystallographic data for IPC-6, IPC-7 and UTL samples is shown for the first time. A dynamic assessment by positron annihilation lifetime spectroscopy (PALS) provided complementary insights, simply distinguishing the enhanced accessibility of the pore network in samples incorporating mesoscale pillars and revealing the presence of a certain fraction of micropores undetected by gas sorption. Nonetheless, subtle differences in the pore size could not be discriminated based on the widely-applied Tao-Eldrup model. The combination of both methods can be useful for the advanced characterization of microporous, mesoporous and hierarchical materials.

Developing New Immunosuppression for the Next Generation of Transplant Recipients: The Path Forward.

The development of new immunosuppressive drugs has slowed markedly over the past several years, and the outlook that improved therapy will be available to the next generation of transplant recipients is bleak. In this viewpoint, the authors outline some of important barriers to new drug development and suggest specific steps that the transplant community can take to overcome them.

Understanding the adsorption mechanism of noble gases Kr and Xe in CPO-27-Ni, CPO-27-Mg, and ZIF-8.

An experimental study of Xe and Kr adsorption in metal-organic frameworks CPO-27-Ni, CPO-27-Mg, and ZIF-8 was carried out. In situ synchrotron X-ray powder diffraction experiments allowed precise determination of the adsorption sites and sequence of their filling with increasing of gas pressure at different temperatures. Structural investigations were used for interpretation of gas adsorption measurements.

Gapless spin liquid ground state in the S = 1/2 vanadium oxyfluoride kagome antiferromagnet [NH4]2[C7H14N][V7O6F18].

The vanadium oxyfluoride [NH(4)](2)[C(7)H(14)N][V(7)O(6)F(18)] (DQVOF) is a geometrically frustrated magnetic bilayer material. The structure consists of S = 1/2 kagome planes of V(4+) d(1) ions with S = 1 V(3+) d(2) ions located between the kagome layers. Muon spin relaxation measurements demonstrate the absence of spin freezing down to 40 mK despite an energy scale of 60 K for antiferromagnetic exchange interactions. From magnetization and heat capacity measurements we conclude that the S = 1 spins of the interplane V(3+) ions are weakly coupled to the kagome layers, such that DQVOF can be viewed as an experimental model for S = 1/2 kagome physics, and that it displays a gapless spin liquid ground state.

Aggressive strategic planning for oral health in Kuwait: a decade of post-war successes.

Strategic planning and implementation of oral health care and disease prevention programmes after the 1990/91 Gulf war are discussed. The key concept was to develop access to care and disease prevention for all Kuwaiti children in government kindergarten/primary schools and to eliminate emphasis on extractions and restorations. Resources were restored to pre-war levels and then increased. Prevention programmes for 150 000 children were established. Prevention funds increased from 7% to 20% of the oral health budget. Prevention-based dentists increased from 9.7% to 28.0% of staff. Rising caries trends were stabilized or reduced by up to 36.8%. Percentage of caries-free primary dentition in children increased up to 37.6%, permanent dentition up to 27.0%. A dentistry school was established.

Aggressive strategic planning for oral health in Kuwait: a decade of post-war successes

Strategic planning and implementation of oral health care and disease prevention programmes after the 1990/91 Gulf war are discussed. The key concept was to develop access to care and disease prevention for all Kuwaiti children in government kindergarten/primary schools and to eliminate emphasis on extractions and restorations. Resources were restored to pre-war levels and then increased. Prevention programmes for 150 000 children were established. Prevention funds increased from 7% to 20% of the oral health budget. Prevention-based dentists increased from 9.7% to 28.0% of staff. Rising caries trends were stabilized or reduced by up to 36.8%. Percentage of caries-free primary dentition in children increased up to 37.6%, permanent dentition up to 27.0%. A dentistry school was established

Adsorption properties of HKUST-1 toward hydrogen and other small molecules monitored by IR.

Among microporous systems metal organic frameworks are considered promising materials for molecular adsorption. In this contribution infrared spectroscopy is successfully applied to highlight the positive role played by coordinatively unsaturated Cu2+ ions in HKUST-1, acting as specific interaction sites. A properly activated material, obtained after solvent removal, is characterized by a high fraction of coordinatively unsaturated Cu2+ ions acting as preferential adsorption sites that show specific activities towards some of the most common gaseous species (NO, CO2, CO, N2 and H2). From a temperature dependent IR study, it has been estimated that the H2 adsorption energy is as high as 10 kJ mol(-1). A very complex spectral evolution has been observed upon lowering the temperature. A further peculiarity of this material is the fact that it promotes ortho-para conversion of the adsorbed H2 species.

Use of echocardiography to assess function of hDAF-transgenic pig cardiac xenografts.

The current standard of hand palpation may not be a sensitive method to detect rejection in heterotopic heart xenotransplants (HHTx). We sought to assess the use of echocardiography to detect rejection of pig heart xenografts. Four cynomolgus monkeys received HHTx from hDAF-transgenic pigs. Immunosuppression was cyclophosphamide induction, cyclosporine, steroids, sodium mycophenolate, alphaGal trisaccharide polymer, +/-soluble complement receptor type 1. Echocardiography was performed immediately after HHTx and three times a week postoperatively. Contractility on echo was scored as 1(none), 2(severely impaired), 3(moderate to severely impaired), 4(moderately impaired), 5(mild to moderately impaired), 6(mildly impaired), or 7(normal). Left ventricle wall thickness (LVWT) was measured in the anterior, inferior, posterior, lateral, and septal walls, the average was calculated. Impaired contractility or increase in LVWT were considered rejection and treated with steroids (solumedrol 15 mg/kg IV for 3-5 days). Palpation score (4-strong to 1-none) was recorded daily. Myocardial biopsies were obtained infrequently. At the time of first rejection, all four monkeys had an increase in LVWT and a decrease in contractility on echocardiography. Steroid treatment enhanced contractility in four monkeys and decreased LVWT in three monkeys. Palpation score remained at four of four during initial rejection episodes. Decrease in contractility and increase in LVWT on echocardiography appear to signify graft injury because steroid treatment results in improvement. Compared to palpation, echocardiography is more sensitive for assessing function of heterotopic pig heart xenografts. Echocardiography has, therefore, the potential to detect and treat early rejection episodes of heterotopic heart xenografts in nonhuman primates. This may help to achieve longer graft survival.

Who is not reassured following benign diagnosis of breast symptoms?

UNLABELLED: Many women fail to be reassured about their breast symptom following benign diagnosis. Identification of the factors contributing to this continued anxiety is important in order that appropriate intervention can be incorporated into the care of women undergoing diagnosis. In this study, we measured levels of anxiety, depression, stress, perceived personal risk of breast cancer, fear of breast cancer treatment and general health anxiety along with clinical and demographic variables in women undergoing investigation of breast symptoms. We then assessed if these factors were associated with reassurance about the breast symptom immediately following benign diagnosis. METHODS: Women attending a specialist 'one-stop' breast clinic completed a questionnaire in the clinic prior to diagnosis and a reassurance measure post-benign breast symptom diagnosis. RESULTS: Post-diagnosis, 67% of women were reassured however, 33% were not reassured about their breast symptom despite a benign diagnosis. Women who were not reassured were more likely to be educated only to high school level and have presenting symptoms of a change in breast shape/dimpling of the breast. There was a trend for women who were not reassured to have breast pain and be diagnosed with a benign breast cyst. Examination of the psychological variables showed that women who were not reassured compared to reassured women had higher levels of health anxiety, perceived stress, fear of breast cancer treatment and general anxiety. Logistic regression analysis entering all the predictors suggests that level of education was the strongest predictor of lack of reassurance following benign diagnosis. CONCLUSION: This study found that a significant proportion of women who undergo investigation and receive a benign diagnosis of their breast symptom experience uncertainty. Our finding that women who were not reassured were more likely to be educated only to high school level suggests that this group may benefit from additional information about breast symptoms and benign diagnosis. Additionally, our results indicate that women with high levels of anxiety, perceived stress and general worry about their health may need further reassurance in the immediate diagnosis phase. Further research focussing on how reassurance is interpreted in the context of women's perceptions about breast symptoms and breast disease is important so that appropriate support can be offered for women undergoing diagnosis of breast symptoms.

Community based schoolchildren's oral health programmes, Kuwait 1985--1998.

AIM: To describe the development of children's oral health programmes in Kuwait and present selected results and expected outcomes based on specific markers. To provide a basis for choosing best outcomes to develop public health policy and implement future programmes. METHOD: Assessment of the health, structural, cost and benefit changes in the oral health sector that resulted from policy decisions and implementation through different approaches in the period 1986--1998. RESULTS: Analysis has provided a basis for selection of appropriate methodologies to be implemented in the country. CONCLUSIONS: The regional programme consisting of full immediate prevention coverage with fluoride lozenges, periodic fluoride rinses, multi-operator care teams, flexible and moveable equipment appears to have provided the best potential within the Kuwait context during this period.

Pirfenidone: A novel anti-fibrotic agent and progressive chronic allograft rejection.

UNLABELLED: In our established model of heterotopic tracheal transplantation, at day 28 following transplantation, obliteration of the lumen is observed, which is histologically similar to that seen in Obliterative Bronchiolitis (OB). Pirfenidone (Pir) is a novel anti-fibrotic agent that causes no immunosuppression, but does downregulate the production of TGF-beta and collagen in vitro. We hypothesized that when used in this in vivo model, that Pir may alter the observed luminal fibrosis and obliteration. METHODS: The treatment groups were: CSA, Pir and CSA, Pir only (n=6 each). Luminal supernatants and tissue were obtained from these groups at day 28. H&E staining was completed, as well as MTS proliferation assays, and TGF-beta ELISA on the fluids. RESULTS: The CSA-Pir combined treatment group was the least fibrogenic in vitro (p<0.001). The TGF-beta levels were elevated in all groups (range 203-372 pg/ml). The H&E staining revealed that the luminal obliteration was less organized in the combined CSA-Pir group. CONCLUSIONS: Our study shows that the combination of CSA-Pir results in a less fibrogenic luminal fluid and a less dense fibrous luminal plug. Pir should be further studied in obliterative airways disease (OAD).

In vitro and in vivo activity and cross resistance profiles of novel ruthenium (II) organometallic arene complexes in human ovarian cancer.

Ruthenium complexes offer the potential of reduced toxicity, a novel mechanism of action, non-cross resistance and a different spectrum of activity compared to platinum containing compounds. Thirteen novel ruthenium(II) organometallic arene complexes have been evaluated for activity (in vitro and in vivo) in models of human ovarian cancer, and cross-resistance profiles established in cisplatin and multi-drug-resistant variants. A broad range of IC50 values was obtained (0.5 to >100 microM) in A2780 parental cells with two compounds (RM175 and HC29) equipotent to carboplatin (6 microM), and the most active compound (HC11) equipotent to cisplatin (0.6 microM). Stable bi-dentate chelating ligands (ethylenediamine), a more hydrophobic arene ligand (tetrahydroanthracene) and a single ligand exchange centre (chloride) were associated with increased activity. None of the six active ruthenium(II) compounds were cross-resistant in the A2780cis cell line, demonstrated to be 10-fold resistant to cisplatin/carboplatin by a mechanism involving, at least in part, silencing of MLH1 protein expression via methylation. Varying degrees of cross-resistance were observed in the P-170 glycoprotein overexpressing multi-drug-resistant cell line 2780AD that could be reversed by co-treatment with verapamil. In vivo activity was established with RM175 in the A2780 xenograft together with non-cross-resistance in the A2780cis xenograft and a lack of activity in the 2780AD xenograft. High activity coupled to non cross-resistance in cisplatin resistant models merit further development of this novel group of anticancer compounds.

Identification and characterization of Magmas, a novel mitochondria-associated protein involved in granulocyte-macrophage colony-stimulating factor signal transduction.

OBJECTIVE: The aim of this study was to identify granulocyte-macrophage colony-stimulating factor (GM-CSF) responsive genes. MATERIALS AND METHODS: Potential GM-CSF responsive genes were identified by comparing the mRNA expression pattern of the murine myeloid cell line PGMD1 grown in either interleukin-3 (IL-3) or GM-CSF by differential display. Human and murine cDNA clones of one of the bands having increased expression in GM-CSF were isolated. mRNA expression of the gene was examined by Northern blot. Immunohistochemistry and studies with a green fluorescent fusion protein were used to determine its intracellular location. Growth factor-stimulated proliferation of PGMD1 cells transfected with constitutively expressed sense and anti-sense cDNA constructs of the gene was measured by 3H-thymidine incorporation. RESULTS: A gene, named Magmas (mitochondria-associated granulocyte macrophage CSF signaling molecule), was shown to be rapidly induced when cells were switched from IL-3 to GM-CSF. Analysis of the amino acid sequence of Magmas showed it contained a mitochondrial signal peptide, but not any other known functional domains. The human and murine clones encode nearly identical 13-kDa proteins that localized to the mitochondria. Magmas mRNA expression was observed in all tissues examined. PGMD1 cells that overexpressed Magmas proliferated similarly to untransfected cells when cultured in IL-3 or GM-CSF. In contrast, cells with reduced protein levels grew normally in IL-3, but had impaired proliferation in GM-CSF. CONCLUSION: Magmas is a mitochondrial protein involved in GM-CSF signal transduction.

Hamster cardiac xenografts are protected against antibody mediated damage, early after transplantation to Lewis rats.

Antibodies play a crucial role in the rejection of xenografts. We tested the hypothesis that xenografts are protected against antibody-mediated attack early after transplantation in a concordant model. We investigated the role of xenoreactive antibodies as a stimulus for protection and the effects of a total blockade of the antibody response by the leflunomide analog malononitrilamide 279. Hamster cardiac xenografts were transplanted to Lewis rat recipients. Second transplants and retransplants of xenografts were performed to untreated rats that had a xenograft in place for 3 d. Untreated rats rejected hamster cardiac xenografts after 4.0 +/- 0.0 d. Significant levels of anti-donor IgM, as measured by flowcytometry, were present on day 3 after transplantation (11.2% +/- 2.8 vs. 1.2% +/- 0.0 on day 0, P < 0.001). 'Fresh' second xenografts transplanted to rats that had a first xenograft in place for 3 d and had anti-hamster antibodies, underwent hyperacute rejection. The first xenografts remained functioning. Xenografts that were removed on day 3 from untreated rats and then retransplanted remained functioning. Xenografts that were removed on d 3 from rats that had been treated with malononitrilamide 279, 15 mg/kg/d and were retransplanted underwent hyperacute rejection. IgM levels at the time of removal were 1.1% +/- 0.5 in these rats and not different from baseline (P = 0.96). We conclude that xenografts are protected against antibody-mediated damage early after transplantation. The presence of anti-donor antibodies might be an essential stimulus for the induction of protection. There seems to be a delicate balance between the injurious and protective effects of antibodies. Treatment strategies that are designed to block antibody formation completely might prevent the induction of protection.

Dental caries experience of disabled children and young adults in Kuwait.

OBJECTIVE: The aim of the study was to assess the caries experience of disabled children and young adults in Kuwait, to set baseline data, and to determine their treatment need. METHOD: Dental caries was scored by surface in accordance with WHO criteria. The study population comprised 832 disabled children and young adults (3-29 years; mean age 12.1 years) who were visually impaired, hearing impaired, had physical handicaps or developmental disorders, attending special needs schools. RESULTS: The proportion of caries free subjects in the primary dentition (3-12-year-old children) was 11.2%. The mean dmft was 5.4, and dmfs 15.2, being highest in the Down's syndrome and lowest in the blind. The proportion of caries-free subjects in permanent dentition, over 5 years of age was 24.2%. The smallest percentage of caries-free subjects was found in the hearing impaired (16.4%) and highest percentage in the blind (35.5%). The mean DMFT was 4.5 and the DMFS 8.7, being highest in the Down's syndrome and lowest in the blind. Prevalence of untreated decay was highest in hearing impaired (86%). The caries experience of first permanent molars represented the largest proportion of the DMFT score (53.6%). In the permanent dentition increasing age, impaired hearing, and poor oral hygiene were significantly associated with caries risk. CONCLUSIONS: Caries experience among this disabled population was clearly higher than among the respective age groups in a previous national population survey. The study confirmed the need for strengthening organised preventive and restorative care for this population in Kuwait.

Coadministration of either cyclosporine or steroids with humanized monoclonal antibodies against CD80 and CD86 successfully prolong allograft survival after life supporting renal transplantation in cynomolgus monkeys.

BACKGROUND: Recent studies have shown some efficacy using monotherapy with monoclonal antibodies (mAb) against CD80 and CD86 receptors after life-supporting renal transplantation in non-human primates. Our study was designed to evaluate the efficacy of combinations of the same mAbs with either microemulsion cyclosporine (CsA) or steroids. METHODS: Unilateral renal transplantation was performed in 16 blood group-matched and MLR-mismatched cynomolgus monkeys that were assigned to four different treatment groups. All monkeys in groups I, II, and IV were treated with the combination of a CD80 (h1F1) and CD86 (h3D1) mAb given at 20 mg/kg each preoperatively, then 5 mg/kg at weekly intervals starting postoperative (po) day 0 until poday 56 (9 doses). In group I the animals (n=4) were treated with mAbs only. In group II (n=4) mAbs were combined with a CsA regimen adjusted daily to maintain target 24 hr trough levels of 150-300 ng/ml CsA for poday 0 to poday 56. In group III (n=4) the animals received CsA monotherapy according to the same regimen as group II. In group IV methylprednisone was administered at 2 mg/kg IV on poday 0-2, then at 0.5 mg/kg/day prednisone per gavage that was and tapered to 0.2 mg/kg/day on which they were maintained until poday 56. All animals were off all immunosuppressive treatment after poday 56 and were then followed until poday 119. RESULTS: The mean survival of groups I-IV was 74 (range 9-119 days), 113 (96-119 days), 39 (22-71 days), and 79 days (6 to 119), respectively. All animals in group I showed clinical evidence of acute severe rejection (fever, creatinine increase, anuria) within the first week posttransplant, including those that retained renal function until poday 119. Only one animal in group II had a moderate clinical rejection during the treatment period and three of four animals survived the intended follow-up period. All animals in group III had multiple biopsy proven or severe clinical rejection episodes within the first 21 days and only one animal survived beyond poday 40. Moderate or severe acute rejection was diagnosed in three of four animals of group IV within the first 28 days post transplant and only one animal survived until poday 119. CONCLUSION: Our data show that combining a calcineurin inhibitor or prednisone with mAbs designed to block costimulatory signals does not antagonize the immunosuppressive efficacy of these mAbs. In addition, combining CsA with mAbs directed against the CD80 and CD86 receptors significantly prolongs graft survival when compared to CsA monotherapy. Therefore clinical trials of humanized mAbs to CD80 and CD86 used in combination with conventional immunosuppression can be considered.