Search

Designing organic saccharide sensors for use in aqueous solution is a nontrivial endeavor. Incorporation of hydrogen bonding groups on a sensor’s receptor unit to target saccharides is an obvious strategy but not one that is likely to ensure analyte-receptor interactions over analyte-solvent or receptor-solvent interactions. Phenylboronic acids are known to reversibly and covalently bind saccharides (diols in general) with highly selective affinity in aqueous solution. Therefore, recent work has sought to design such sensors and understand their mechanism for allowing fluorescence with bound saccharides. In past work, binding orientations of several saccharides were determined to dimethylaminomethylphenylboronic acid (DMPBA) receptors with an anthracene fluorophore; however, the binding orientation of d-fructose to such a sensor could not be determined. In this work, we investigate the potential binding modes by generating 20 possible bidentate and six possible tridentate modes between fructose and DMPBA, a simplified receptor model. Gas phase and implicit solvent geometry optimizations, with a myriad functional/basis set pairs, were carried out to identify the lowest energy bidentate and tridentate binding modes of d-fructose to DMPBA. An interesting hydrogen transfer was observed during selected bidentate gas phase optimizations; this transfer suggests a strong sharing of the hydrogen atom between the boronate hydroxyl and amine nitrogen.

AimsThe Bereiter trochleoplasty has been used in our unit for 12 years to manage recurrent patellar instability in patients with severe trochlea dysplasia. The aim of this study was to document the outcome of a large consecutive cohort of patients who have undergone this operation.Patients and MethodsBetween June 2002 and August 2013, 214 consecutive trochleoplasties were carried out in 185 patients. There were 133 women and 52 men with a mean age of 21.3 years (14 to 38). All patients were offered yearly clinical and radiological follow-up. They completed the following patient reported outcome scores (PROMs): International Knee Documentation Committee subjective scale, the Kujala score, the Western Ontario and McMaster Universities Arthritis Index score and the short-form (SF)-12. ResultsOutcomes were available for 199 trochleoplasties in 173 patients giving a 93% follow-up rate at a mean of 4.43 years (1 to 12). There were no infections or deep vein thromboses. In total, 16 patients reported further patella dislocation, giving an 8.3% rate of recurrence. There were 27 re-operations, giving a rate of re-operation of 14%. Overall, 88% were satisfied with the operation and 90% felt that their symptoms had been improved. ConclusionAll PROMs improved significantly post-operatively except for the mental component score of the SF-12. Trochleoplasty performed using a flexible osteochondral flap is an effective treatment for recurrent patellar instability in patients with severe trochlea dysplasia and gives good results in the medium term.Cite this article: Bone Joint J2017;99-B:344–50.

We explored variables likely to affect health of Agassiz's desert tortoises (Gopherus agassizii) in a 1,183-km2study area in the central Mojave Desert of California between 2005 and 2008. We evaluated 1,004 tortoises for prevalence and spatial distribution of 2 pathogens, Mycoplasma agassiziiand M. testudineum, that cause upper respiratory tract disease. We defined tortoises as test-positive if they were positive by culture and/or DNA identification or positive or suspect for specific antibody for either of the two pathogens. We used covariates of habitat (vegetation, elevation, slope, and aspect), tortoise size and sex, distance from another test-positive tortoise, and anthropogenic variables (distances to roads, agricultural areas, playas, urban areas, and centroids of human-populated census blocks). We used both logistic regression models and regression trees to evaluate the 2 species of Mycoplasmaseparately. The prevalence of test-positive tortoises was low: 1.49% (15/1,004) for M. agassiziiand 2.89% (29/1,004) for M. testudineum. The spatial distributions of test-positive tortoises for the 2 Mycoplasmaspecies showed little overlap; only 2 tortoises were test-positive for both diseases. However, the spatial distributions did not differ statistically between the 2 species. We consistently found higher prevalence of test-positive tortoises with shorter distances to centroids of human-populated census blocks. The relationship between distance to human-populated census blocks and tortoises that are test-positive for M. agassiziiand potentially M. testudineummay be related to release or escape of captive tortoises because the prevalence of M. agassiziiin captive tortoises is high. Our findings have application to other species of chelonians where both domestic captive and wild populations exist. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Body condition score is used as a management tool to predict competency of reproduction in beef cows. Therefore, a retrospective study was performed to evaluate association of BCS at calving with subsequent pregnancy rate, days to first postpartum ovulation, nutrient status (assessed by blood metabolites), and calf BW change in 2- and 3-yr-old cows (n = 351) managed and selected to fit their environment of grazing native range over 6 yr at the Corona Range and Livestock Research Center, Corona, NM. Cows were managed similarly before calving, without manipulation of management, to achieve predetermined BCS at parturition. Palpable BCS (scale of 1 to 9) were determined by 2 experienced technicians before calving. Cows were classified to 1 of 3 BCS groups prior calving: BCS 4 (mean BCS = 4.3 ± 0.02), 5 (mean BCS = 5.0 ± 0.03), or 6 (mean BCS = 5.8 ± 0.06). Cows were weighed weekly after calving and serum was collected once weekly (1 yr) or twice weekly (5 yr) for progesterone analysis to estimate first postpartum ovulation beginning 35 d postpartum. Year effects also were evaluated, with years identified as either above or below average precipitation. Days to first postpartum ovulation did not differ among calving BCS groups (P = 0.93). Pregnancy rates were not influenced by calving BCS (P = 0.83; 92%, 91%, 90% for BCS 4, 5, and 6, respectively). Days to BW nadir was not influenced by BCS at calving (P = 0.95). Cow BW was different at all measuring points (P < 0.01) with BCS 6 cows having the heaviest BW and cows with BCS 4 the lightest. Cows with calving BCS 4 and 5 lost more (P = 0.06) BW from the initiation of the study to the end of breeding than cows with BCS 6. However, cow BW change at all other measurement periods was not different (P ≥ 0.49) among calving BCS groups. Serum glucose and NEFA concentrations were not influenced by calving BCS (P ≥ 0.51). Calf BW at birth (P = 0.60), branding (55-d BW; P = 0.76), and weaning (205-d BW; P = 0.60) were not impacted by cow calving BCS. Body condition score did not influence overall pregnancy rates, indicating that young cows can have a reduced BCS and still be reproductively punctual. Therefore, these results indicate that reproductive performance of young cows with reduced BCS may not be affected when managed in extensive range conditions.

AbstractThis paper explores the application of ERM-style techniques to pension funds. It uses the term ‘entity-wide risk management’ rather than ‘enterprise risk management’, even though both have the same acronym (‘ERM’), because many pension funds do not view themselves as business ‘enterprises’ as such. Some of the techniques that business enterprises have for managing risk (e.g. raising new capital from shareholders or branching into new business areas if existing ones have unattractive risk-reward characteristics) may not be open to many pension funds. The paper argues that the holistic approach to risk management (and governance) that is a hallmark of ERM is as appropriate to pension funds as it is to any other type of entity. This is the case whether the fund is defined benefit or defined contribution in nature, or a hybrid. It is also the case whether the ‘entity’ is deemed to be the fund itself, the sponsor or the two combined. Indeed, there are aspects of pension arrangements, such as the relationship between the fund and its sponsor, that lend added impetus to the use of ERM-style techniques in practical pension fund management.

AbstractThe Management Board of the UK Actuarial Profession is undertaking a thought leadership cross-practice research project on the use of discount rates by UK actuaries. The timing for this research is particularly appropriate as there is a convergence of interest in discount rates from within and outside of the Profession. Discount rates are at the heart of most actuarial calculations and are of significant public interest. As part of this project the Management Board wants a full and open debate on the significant issues and this paper is the next step in stimulating that debate, giving another opportunity to influence the future direction of the project.The Management Board set up a small cross-practice steering committee to drive the project. The Discount Rate Steering Committee identified five areas of work that would be needed to achieve the project's overall objectives:(1)A survey of current practices.(2)A survey of existing research and debate.(3)Developing a common language for communicating discount rates and risk.(4)Developing a common framework for the future where appropriate.(5)Considering the impact of any changes.Although the Profession does not set standards for technical work it still has a significant role for undertaking research in the public interest which supports the competence of its members and the furtherance of actuarial science.Chinu Patel and Chris Daykin were commissioned to undertake the first part of this work and they presented their preliminary output at a forum of thought leaders across the Profession and externally on 23 March 2010. Their report “Actuaries and Discount Rates” was subsequently published in May 2010 and presented the results of their initial research into past and current practice in the setting of discount rates in the UK, and a survey of existing research and debate. A summary of that report is included in Section 2 of this paper.Following consultation both within and outside the Actuarial Profession, this interim paper now takes forward the ideas and initial steps developed by Patel & Daykin and looks at developing a common language and framework for using discount rates in actuarial work. The Discount Rate Steering Committee is making a number of recommendations to the Profession which are intended to help actuaries speak clearly and with authority in future debates about discount rates and to support actuaries in communicating impartially and effectively. The recommendations are set out in Section 6 of the report following the development of the framework in Sections 3–5. As part of further developing the recommendations to the Profession, the Discount Rate Steering Committee is seeking views from stakeholders from inside and outside of the Profession. This will be undertaken throughout January and February 2011 and, as part of this process, the report will be presented at sessional research events in Edinburgh (17 January 2011) and London (31 January 2011). The Discount Rate Steering Committee is committed to seeking feedback on the recommendations and hopes this paper will give those inside and outside the Profession an opportunity to add to the dialogue so that as wide a range of potential views as possible is heard.In this paper, the steering committee has concentrated on the more technical aspects of developing a framework for communicating discount rates and associated risks and the report is aimed primarily at actuaries. But the committee is mindful of the need to help actuaries communicate more clearly with those outside the Profession. During the first half of 2011, the steering committee will therefore concentrate on producing a document in less technical language to help non-actuaries understand the issues around the selection and use of discount rates and to help actuaries in their communication with stakeholders.

Reproductive performance in young beef cows is often compromised due to a mismatch of physiological demands and suboptimal environmental conditions. Studies conducted at the Corona Range and Livestock Research Center from 2000 to 2007 evaluated 3 postpartum supplement strategies that varied in the amount of glucogenic potential (GP) supplied. Reproductive variables, milk production, and serum metabolites were used to assess supplement effectiveness and economics associated with 2- and 3-yr-old beef cows (n = 379) grazing native range. Supplements were individually fed twice/week at 1,135 g/d (2003 to 2004) or 908 g/d (all other years) and provided 1) 327 g of CP, 109 to 118 g of RUP (CON); 2) 327 to 341 g of CP, 142 to 157 g of RUP (RUP); or 3) 327 g of CP, 151 to 173 g of RUP + 40 to 100 g of propionate salt (PS; RUP+PS). Ultimately, total GP for CON, RUP, and RUP+PS was 44 to 47, 57 to 70, and 93 to 141 g, respectively. Blood samples were collected once/week (2000) or twice/week (2001 to 2007) for progesterone analysis to estimate days to resumption of estrus. Cows were exposed to bulls for 60 d or less, and pregnancy was confirmed by rectal palpation at weaning. Days to resumption of estrus after calving decreased linearly (P= 0.02), resulting in an increased pregnancy rate (P= 0.03) with increasing GP. Milk production exhibited a quadratic (P= 0.04) response to increasing GP, with cows fed RUP producing the most amount of milk. However, a linear decrease (P= 0.07) in days from BW nadir to estrus was found with increasing GP. Total kilograms of calf weaned per cow exposed for the supplemental year and subsequent year was increased linearly (P= 0.07) with increased GP. The improvement in pregnancy rate by supplementing RUP+PS resulted in an increase in total revenue of 18% compared with CON-fed cows and 9.5% compared with RUP-fed cows in the subsequent year after supplementation. These data suggest feeding young cows additional GP in the form of PS allows for partitioning of nutrients away from milk production and toward reproduction, allowing for increased profitability by increasing pregnancy rates and decreasing days to resumption of estrus.

Terahertz spectroscopy has been investigated as a technique for concealed explosives detection since spectroscopic signatures in common explosives were first identified almost 10 years ago. This paper explores the progress towards practical development of the technology and the physical basis of the challenges involved in creating a deployable person-borne IED detection system. We conclude that, despite the theoretical potential of terahertz to provide a safe, through-barrier spectroscopic detection technique, this is unlikely to be possible in practice. The relatively weak and broad explosives features tend to be masked by the combined effects of atmospheric water vapor absorption, barrier attenuation and scattering from both clothing and the target explosives. Imaging at the lower end of the terahertz frequency range, although not offering the same specificity, is a more promising technique for security applications.

Supplementing CP and propionate salts (PS) may improve economic returns in young range beef cows by increasing the dietary supply of glucogenic precursors. A 3-yr study conducted at Corona Range and Livestock Research Center (Corona, NM) from February to mid-July in 2005 (n = 80), 2006 (n = 81), and 2007 (n = 80) evaluated days to first estrus, calf weaning weight, BW change, and metabolic responses in 2- and 3-yr-old postpartum cows grazing native range. Cows were individually fed one of three 36% CP supplement treatments after parturition, with increasing glucogenic potential (GP) supplied by RUP and PS. Supplements were isoenergetic and fed at a rate of 908 g/cow per day twice weekly. Supplementation was initiated 7 d after calving and continued for an average of 95 d. Supplement treatments provided 1) 328 g of CP, 110 g of RUP and 0 g of PS (PS0); 2) 328 g of CP, 157 g of RUP, and 40 g of PS (PS40); or 3) 329 g of CP, 158 g of RUP, and 80 g of PS (PS80). Ultimately, PS0, PS40, and PS80 provided 44, 93, and 124 g of GP, respectively. Body weight was recorded weekly and serum was collected twice weekly for progesterone analysis to estimate days to first estrus. Cows were exposed to bulls for 60 d or less beginning in mid-May. Days to first estrus exhibited a quadratic (P= 0.06) response to GP resulting from the fewest days to first estrus with the consumption of PS40. Pregnancy rates were 88, 96, and 94% for cows fed PS0, PS40, and PS80, respectively (P= 0.11). Total kilograms of calf weaned per cow exposed to bulls for the supplementation and following year increased quadratically (P= 0.09). However, supplement did not affect milk composition or yield (P≥ 0.53). Serum acetate half-life decreased linearly (P= 0.08) with increasing GP in 2007. Predicted margins were the greatest (quadratic; P= 0.03) for cows fed PS40. Even though supplement costs were greater for PS40 and PS80, cows fed PS40 had increased profits ($33.47/cow) compared with cows fed PS0 and PS80. This study implies that young postpartum cows fed additional glucogenic precursors may have improved reproductive efficiency and may wean more calf weight per cow exposed to breeding.

Recurrent dislocation after reconstructive hip surgery remains a challenging problem to treat. Constrained acetabular components can provide an excellent solution, in selected patients. Failure of constrained components may still occur despite excellent component implantation and occurs at the liner-shell and shell-bone interfaces usually as a result of trauma or aseptic loosening. We describe the failure of a Trident bipolar acetabular component at its bipolar/insert interface, a previously unreported mode of failure.

1.A LimulusSMARTTMcDNA library screening resulted in the cloning of four syntaxin 1 homologs (referred to as Limulussyntaxin [Lim-syn] 1A, 1B, 1C, and 1D) (Wang, Y., Cao, Z., Xu, W., Kemp, M. D., McAdory, B. S., Newkirk, R. F., Ivy, M. T., and Townsel, J. G. (2004). Gene326:189–199) and two novel intron-retaining syntaxin 1-like variants, designated Limulussyntaxin variant [Lim-synV] 1A/1C and Lim-synV 1B/1D.2.The variants exhibited high amino acid sequence identity with the four syntaxin 1 homologs. Specifically, Lim-synV 1A/1C and Lim-synV 1B/1D were homologous to Lim-syn 1A/1C and Lim-syn 1B/1D, respectively. Surprisingly, both Lim-synV 1A/1C and 1B/1D are unusual in that each has a poly A+ tail, an intron, and the common splice motif “GT–AG” at the intron–exon boundary. Exons one and two on the complementary transcript of Lim-synV 1B/1D are separated by a 150 bp intron beginning at #95/96 of the predicted sequences for Lim-syn 1B and 1D, respectively.3.In contrast, examination of the approximately 3.17 kb Lim-synV 1A/1C clone indicated the inclusion of an insert of 1120 base pairs (bp) beginning at codon #37/38 of the predicted Lim-syn 1A and 1C cDNAs’ open reading frames (ORFs). Further, the intron sequence of Lim-synV 1A/C contained multiple stop codons and showed no significant homology to other known sequences as determined by a search of the GenBank database. Thus, the focus of this paper will be Lim-synV 1B/D exclusively.4.To substantiate that an intron is retained in the full-length mRNA, two types of syntaxin cDNA fragments for Lim-syn 1B/D were generated by RT-PCR and analyzed on Northern blots. The products generated were a mixture of intron-retaining, as well as intron-spliced products. The syntaxin-like variants that retained the intron presumably are derived from a mRNA molecule that has not undergone splicing.5.Although the significance of such intron-containing mRNAs in Limulushas not yet been elucidated, future studies of such variants may serve to broaden our knowledge concerning established splicing mechanisms as well as to focus attention on nonconventional concepts about gene product regulation.1.A LimulusSMARTTMcDNA library screening resulted in the cloning of four syntaxin 1 homologs (referred to as Limulussyntaxin [Lim-syn] 1A, 1B, 1C, and 1D) (Wang, Y., Cao, Z., Xu, W., Kemp, M. D., McAdory, B. S., Newkirk, R. F., Ivy, M. T., and Townsel, J. G. (2004). Gene326:189–199) and two novel intron-retaining syntaxin 1-like variants, designated Limulussyntaxin variant [Lim-synV] 1A/1C and Lim-synV 1B/1D.2.The variants exhibited high amino acid sequence identity with the four syntaxin 1 homologs. Specifically, Lim-synV 1A/1C and Lim-synV 1B/1D were homologous to Lim-syn 1A/1C and Lim-syn 1B/1D, respectively. Surprisingly, both Lim-synV 1A/1C and 1B/1D are unusual in that each has a poly A+ tail, an intron, and the common splice motif “GT–AG” at the intron–exon boundary. Exons one and two on the complementary transcript of Lim-synV 1B/1D are separated by a 150 bp intron beginning at #95/96 of the predicted sequences for Lim-syn 1B and 1D, respectively.3.In contrast, examination of the approximately 3.17 kb Lim-synV 1A/1C clone indicated the inclusion of an insert of 1120 base pairs (bp) beginning at codon #37/38 of the predicted Lim-syn 1A and 1C cDNAs’ open reading frames (ORFs). Further, the intron sequence of Lim-synV 1A/C contained multiple stop codons and showed no significant homology to other known sequences as determined by a search of the GenBank database. Thus, the focus of this paper will be Lim-synV 1B/D exclusively.4.To substantiate that an intron is retained in the full-length mRNA, two types of syntaxin cDNA fragments for Lim-syn 1B/D were generated by RT-PCR and analyzed on Northern blots. The products generated were a mixture of intron-retaining, as well as intron-spliced products. The syntaxin-like variants that retained the intron presumably are derived from a mRNA molecule that has not undergone splicing.5.Although the significance of such intron-containing mRNAs in Limulushas not yet been elucidated, future studies of such variants may serve to broaden our knowledge concerning established splicing mechanisms as well as to focus attention on nonconventional concepts about gene product regulation.

ABSTRACTThis paper considers the impact that the current trend towards fair valuation of assets and liabilities is likely to have on risk measurement and management practices within the financial services industry. The paper analyses the different sorts of risks faced by organisations such as asset managers, pension funds, banks and insurers, and seeks to identify how their approach to the measurement and management of these sorts of risks might change as fair valuation becomes more entrenched. It argues that what it describes as traditional ‘time series’ based risk measurement is likely to be progressively displaced over time by a greater emphasis on what the paper refers to as ‘derivative pricing’ (or ‘fair value’ or ‘market consistent’) based risk modelling. It comments on the trend towards liability driven investment. The paper focuses on ‘financial’ risks (market, credit, liquidity and, more generally, asset/liability risk) rather than ‘operational’ risks, whilst noting that the dividing line between the two can be open to interpretation. Insurance risk is seen as in some respects straddling both camps.

Abstract. Leonardo's studies of cardiovascular systems, in more than 50 surviving pages from two phases of his research (around 1508-1509 and 1513), are a clear demonstration of his observational genius and progressive deduction of cardiac mechanics and the vascular system. He carried out a detailed hemodynamic study of the aortic valve motion and the role of the Sinus of Valsalva in the closure dynamics of the aortic valve, and he accurately correlated the formation of vortices with the separation of a retarded (shear) layer from the lips of the leaflets. In-vivo verification of vortex formation in the Sinus of Valsalva during the systolic phase awaited the application of modern phase-averaged magnetic resonance imaging techniques. Did Leonardo actually build the glass model he twice mentioned, thus performing the first scientific flow visualization of impulsive vortex formation or other fluid mechanical phenomena? Evidence in support of this possibility can be found in both the unusually schematic style he employed for this suite of drawings and the recent flow imaging results obtained in our laboratory through laser-based imaging techniques.

ABSTRACTThis paper takes an overview of the potential roles and responsibilities of pension scheme actuaries in the United Kingdom in relation to defined contribution (DC) schemes.First it summarises briefly the background to UK retirement provision and in particular the move to DC arrangements. The paper then compares and contrasts the pension scheme actuary's current role in both defined benefit (DB) and DC schemes. This is then developed to consider what further statutory roles there may be for actuaries in DC schemes.The paper challenges the profession to champion the public interest by seeking clarity and simplification, and finally considers the impact on actuarial employment.

The repetitive sequence of Leishmania majorgene B protein (GBP) has previously been shown to be a useful tool in the diagnosis of cutaneous leishmaniasis (CL). Here, we have assessed enzyme-linked immunosorbent assays (ELISAs) using recombinant L. donovaniGBP (rGBP) and a peptide sequence of L. donovaniGBP (GBPP) in the diagnosis of L. donovaniinfections in Sudan. The sensitivity of the rGBP ELISA in diagnosing visceral leishmaniasis (VL) and post kala-azar dermal leishmaniasis (PKDL) was 92% and 93%, respectively. In contrast, the sensitivity of the GBPP ELISA was 55% for VL and 63% for PKDL. Plasma antibody reactivity of donors with VL and PKDL remained high for an extended period after the end of treatment. Antibody-reactivity to rGBP and GBPP was detected in 71% and 14% of plasma samples from CL patients, respectively. Plasma from healthy Sudanese donors living in an area endemic for malaria but free of leishmaniasis was negative in both assays.

Objective To compare cardiac troponin T release and lactate metabolism in coronary sinus and arterial blood during uncomplicated coronary grafting on the beating heart with conventional coronary grafting using cardiopulmonary bypass. Design A prospective observational study with simultaneous sampling of coronary sinus and arterial blood: before and 1, 4, 10, and 20 minutes after reperfusion for analysis of cardiac troponin T and lactate. Cardiac troponin T was also analysed in venous samples taken 3, 6, 24, 48, and 72 hours after surgery. Setting Cardiac surgical unit in a tertiary referral centre. Patients 18 patients undergoing coronary grafting on the beating heart (10 single vessel and eight two-vessel grafting) and eight undergoing two-vessel grafting with cardiopulmonary bypass. Results Cardiac troponin T was detected in coronary sinus blood in all patients by 20 minutes after beating heart coronary artery surgery before arterial concentrations were consistently increased. Peak arterial and coronary sinus cardiac troponin T values on the beating heart during single (0.03 (0 to 0.05) and 0.09 (0.07 to 0.16 μg/l, respectively) and two-vessel grafting (0.1 (0.07 to 0.11) and 0.19 (0.14 to 0.25) μg/l) were lower than the values obtained during cardiopulmonary bypass (0.64 (0.52 to 0.72) and 1.4 (0.9 to 2.0) μg/l) (p &lt; 0.05). The area under the curve of venous cardiac troponin T over 72 hours for two-vessel grafting on the beating heart was less than with cardiopulmonary bypass (13 (10 to 16) v 68 (26 to 102) μg.h/l) (p &lt; 0.001). Lactate extraction began within one minute of snare release during beating heart coronary surgery while lactate was still being produced 20 minutes after cross clamp release following cardiopulmonary bypass. Conclusions Lower intraoperative and serial venous cardiac troponin T concentrations suggest a lesser degree of myocyte injury during beating heart coronary artery surgery than during cardiopulmonary bypass. Oxidative metabolism also recovers more rapidly with beating heart coronary artery surgery than with conventional coronary grafting. Coronary sinus cardiac troponin T concentrations increased earlier and were greater than arterial concentrations during beating heart surgery, suggesting that this may be a more sensitive method of intraoperative assessment of myocardial injury.

Controlled trials in a number of countries have documented benefits from different types of in- home assessment and treatment programs for various subgroups of elderly persons. We have developed a program to test, using a randomized controlled design, the concepts of in- home comprehensive geriatric assessment (CGA) coupled with follow- up, health education, and preventive care in an urban United States community. The intervention includes yearly in- home CGA by geriatric nurse practitioners (GNPs), who provide, following discussions with physician geriatricians, lists of specific recommendations for health and well-being enhancement. The GNPs provide follow-up visits quarterly and regular telephone contacts to improve compliance. We recruited for our trial 414 home-living subjects aged 75 years and over, 215 randomized to the intervention group and 199 to the control group. Subjects were generally representative of the overall elderly population of the city of Santa Monica, a seaside suburb of Los Angeles. Extensive baseline data (medical, functional, psychosocial and environmental) were collected from subjects prior to randomization, using validated instruments whenever possible. Follow- up data were collected from each subject every 4 months by trained research assistants throughout the 3-year intervention follow- up period. Our study was designed to assess effects of the intervention on the hypothesized outcomes of health status, functional status, psychosocial parameters, and service utilization. Careful documentation of the intervention will enhance our ability to make process- outcome comparisons. Preliminary analysis reveals that the in- home CGA uncovered many important health deficits for most subjects resulting in a number of substantial recommendations. We are confident that when it is completed, this study will succeed in answering important remaining questions about the feasibility and effectiveness of establishing a geriatric in- home prevention and health promotion program in the United States based on principles of CGA. (Aging Clin. Exp. Res. 6: 105- 120, 1994).

Acemannan is a polydispersed beta-(1,4)-linked acetylated mannan with antiviral properties. It is an immunomodulator, and studies in our laboratory have shown that it causes activation of macrophages. Inducible NO synthase is generally expressed after transcriptional induction and is known to mediate some of the cytotoxic action of activated macrophages. Acemannan, in the presence of interferon-gamma, greatly increased the synthesis of NO in RAW 264.7 cells. This increase was preceded by increased expression of mRNA for the inducible form of macrophage NO synthase. Preincubation with pyrrolidine dithiocarbamate inhibited the induction, indicating the involvement of nuclear factor-kappa B. These results suggest that acemannan causes the activation of macrophages by increasing the level of NO synthase at the level of transcription.

Abstract Objective To determine whether a single blood test for the measurement of C reactive protein, or troponin I or T concentrations could be used to stratify patients with intractable unstable angina awaiting transfer for coronary angiography by correlating these values with coronary anatomy and transient myocardial ischaemia. Design Prospective study. Setting Tertiary cardiac unit. Patients All patients admitted to their local hospital with ischaemic chest pain, uncontrolled by medical treatment, in whom acute myocardial infarction had been excluded by serial measurement of creatine kinase and lack of Q waves on ECG. Intervention Coronary angiography and ST segment monitoring for 24 hours. Main outcome measures Concentrations of C reactive protein, troponins T and I, coronary anatomy, presence of transient myocardial ischaemia. Results Median C reactive protein, troponin I, and troponin T concentrations were 17.1 mg/dl (4.8 to 203.9), 0.05 μg/l (0 to 7.8), and 0.0 μg/l (0 to 2.51), respectively. Seven patients (10%) had normal coronaries and 14, 20, and 31 had one, two, or three vessel coronary disease, respectively. Nineteen (26%) had transient myocardial ischaemia, 33 (46%) had complex lesion morphology, and six (8%) had intracoronary thrombus. Of the three markers, troponin T alone was higher in patients with multivessel disease (p &lt; 0.05) and in those with transient myocardial ischaemia (p &lt; 0.05), but there was no significant relation between C reactive protein, troponin T or I and lesion morphology or thrombus. Conclusions In patients transferred to a tertiary centre with intractable chest pain, C reactive protein and troponin I are not predictive of transient myocardial ischaemia or lesion morphology, both of which are surrogate markers of outcome. Troponin T is, however, raised in patients with multivessel disease or transient myocardial ischaemia. These serum protein assays cannot be used to stratify the risk of patients with unstable angina who are awaiting transfer to the tertiary centre.

The synthesis of nitrate reductase and its incorporation into the cytoplasmic membrane of Escherichia coli strain A1004a (5-aminolaevulinic acid auxotroph) does not require synthesis of cytochrome b. The synthesis of the apoprotein(s) of the cytochrome b of the respiratory pathway from NADH to nitrate appears to be inhibited by the absence of haem. No member of the respiratory pathway from NADH to oxygen is capable of reducing nitrate reductase directly. The site on nitrate reductase that oxidizes FMNH2 is located on the cytoplasmic aspect of the cytoplasmic membrane.

The product of the reaction catalysed by hexose phosphate synthase prepared from Methylococcus capsulatus was dephosphorylated and the sugar moiety purified. The sugar and derivatives were compared by various chromatographic and other methods with authentic samples of allulose (psicose), d-erythro-l-glycero-3-hexulose and d-erythro-d-glycero-3-hexulose. The sugar is not allulose, as was previously thought on the basis of less extensive evidence (Kemp & Quayle, 1966), but is in fact d-erythro-l-glycero-3-hexulose (d-arabino-3-hexulose). This identification is consistent with recent studies which have shown that hexose phosphate synthase catalyses the condensation of formaldehyde with d-ribulose 5-phosphate rather than with d-ribose 5-phosphate (Kemp, 1972).

ObjectiveTo investigate whether ischaemic preconditioning could reduce myocardial injury, as manifest by troponin T release, in patients undergoing elective coronary artery bypass surgery.DesignRandomised controlled trial.SettingCardiothoracic unit of a tertiary care centre.PatientsPatients with three vessel coronary artery disease and stable angina admitted for first time elective coronary artery bypass surgery were invited to take part in the study; 33 patients were randomised into control or preconditioning groups.InterventionPatients in the preconditioning group were exposed to two additional three minute periods of myocardial ischaemia at the beginning of the revascularisation operation, before the ischaemic period used for the first coronary artery bypass graft distal anastomosis.Main outcome measureSerum troponin T concentration at 72 hours after cardiopulmonary bypass.ResultsThe troponin T assays were performed by blinded observers at a different hospital. All patients had undetectable serum troponin T (&lt; 0·1 μg/l) before cardiopulmonary bypass, and troponin T was raised postoperatively in all patients. At 72 hours, serum troponin T was lower (P = 0·05) in the preconditioned group (median 0·3 μg/l) than in the control group (median 1·4 μg/l).ConclusionsThe direct application of a preconditioning stimulus in clinical practice has been shown, for the first time, to protect patients against irreversible myocyte injury.

The glycosylation patterns of the gp70 glycoproteins of xenotropic and dualtropic murine leukemia virus (MuLV) were compared with those of ecotropic viruses. Ecotropic viruses contain a large glycopeptide size class designated G1 (molecular weight, approximately 5100), and such glycopeptides were not detected in xenotropic viruses grown in mink cells nor in dual-tropic viruses grown in mouse or mink lung cells. Both xenotropic and dual-tropic MuLV had glycopeptide size classes designated G2, G3, and G4 (molecular weights, approximately 2900, 2,200, and 1,500, respectively). G2 glycopeptides of xenotropic and dual-tropic MuLV were shown to be resistant to endo-beta-N-acetylglucosaminidase H, whereas G3 and G4 glycopeptides were susceptible. The relative abudance of glycopeptide G3 was increased in xenotropic and dual-tropic viruses as compared with ecotropic viruses, whereas the relative amount of G4 was decreased in xenotropic viruses. The similarity in the glycosylation patterns of a number of xenotropic and dual-tropic viruses suggests that glycosylation sites are highly conserved within the env gene products of each of these classes of viruses.

Polyacrylamide gel electrophoretic analysis and immunoprecipitation were used to study glycoproteins from purified Rauscher murine leukemia virus (R-MuLV) and from AKR thymic lymphoblastoid cell membranes. In addition to gp70, a minor glycoprotein of approximately 52,000 daltons (gp52) was demonstrated in purified R-MuLV preparations, which was antigenically related to gp70. Analysis of R-MuLV glycopeptides obtained after exhaustive Pronase digestion showed that gp70 has at least two different glycopeptide size classes with molecular weights of 5,100 and 2,900, respectively. gp52, however, contained only a single glycopeptide size class of approximately 5,100 daltons, indicating that the two glycoproteins contain distinct carbohydrate components. Trypsin treatment of R-MuLV converted gp70 into a product with a molecular mass of approximately 52,000 daltons as well as a 45,000-dalton minor product, with little effect on virus infectivity. Similarly, trypsin treatment of 125I-labeled glycoproteins derived from AKR mouse lymphoblastoid cell membranes generated fragments antigenically related to gp70 and similar in size to those obtained by trypsin treatment of R-MuLV. In both cases, the appearance of cleavage products was accompanied by a decrease in gp70 during trypsin treatment. The occurrence of glycosylated components antigenically related to gp70 in AKR membrane glycoprotein preparations and in purified R-MuLV preparations which were similar to those generated by trypsin treatment supports the concept that these minor components arise from proteolytic cleavage of gp70.

Introduction: The vulnerability of pediatric myocardium to ischemia is poorly documented in the clinical setting. Methods: Serial measurements of serum concentrations of myoglobin, the MB isoenzyme of creatine kinase, and cardiac troponins T and I and their respective areas under the curve were obtained, with particular reference to age and ischemic time, in 80 children undergoing cardiac operations. Sixteen (the control group) did not require cardiopulmonary bypass and 64 did. Results: In the control group there were increases (p < 0.01) in myoglobin and creatine kinase MB isoenzyme but no increase in cardiac troponin T or I; by contrast, the group treated with cardiopulmonary bypass had significant increases in all four markers but with differing temporal patterns. Younger age (especially <12 months) was a highly significant explanatory variable only for the release of cardiac troponins T and I, and ischemic time was a significant explanatory variable for the release of creatine kinase MB isoenzyme, cardiac troponins T and I, but not myoglobin. In comparison with previous studies in adults, creatine kinase MB and cardiac troponin T concentrations were three times greater in children than in adults. Conclusions: This study supports the specificity of cardiac troponins T and I as markers of myocardial injury after pediatric cardiac operations and defines the importance of age and ischemic time in determining their release. In comparison with previous data in adults, our results raise the possibility that the pediatric heart may be more vulnerable to the effects of ischemia and reperfusion. Cardiac troponins will permit comparison of new myocardial protective strategies or other potentially therapeutic myocardial interventions. (J Thorac Cardiovasc Surg 1997;113:728-35)

Background Cystic fibrosis related diabetes (CFRD) has become increasingly common with the increasing longevity of patients with cystic fibrosis. The diagnosis of CFRD is important as its development may lead to a clinical deterioration which may be reversed with treatment. The oral glucose tolerance test (OGTT) is the method of choice in the diagnosis of CFRD, but performing OGTTs on all patients is inconvenient for patients and labour intensive for staff. The aim of this study was to identify a more selective approach in performing OGTTs in the diagnosis of CFRD based on the use of a combination of clinical and biochemical criteria. Methods Clinically stable adult patients with cystic fibrosis not known to be diabetic attending the Royal Brompton Hospital Cystic Fibrosis Clinic for their annual review were invited to return within a month to have an OGTT. The result of the OGTT was compared with the results of tests performed during the annual review. The sensitivities and specificities of various methods used in the screening or diagnosis of CFRD were determined using OGTT as the "gold standard" diagnostic method. The combination of clinical and biochemical criteria which resulted in the highest sensitivity and specificity in the diagnosis of CFRD was determined. Results Between August 1996 and May 1997 122 patients became eligible for the study, 91 of whom agreed to take part. The number of patients with normal, impaired, and diabetic glucose tolerance was 58 (64%), 21 (23%), and 12 (13%), respectively. When used alone, abnormal glycosylated haemoglobin (HbA1c) was found to have the highest sensitivity (83%; 95% CI 62 to 100) in the diagnosis of CFRD. The combination of an abnormal random blood glucose and/or abnormal HbA1c and/or symptoms of hyperglycaemia or weight loss was found to have the highest sensitivity (92%; 95% CI 76 to 100) in the diagnosis of CFRD. The specificity of this combination in the diagnosis of CFRD was 79% (95% CI 70 to 88). By selectively performing OGTTs in patients with one or more of the criteria cited above, 11 of the 12 patients with OGTT defined diabetes would have been identified. Conclusions Patients with cystic fibrosis already have to undergo a large number of routine investigations. The selective approach in performing OGTTs described here has the potential to identify the majority of patients with CFRD without the need to perform this investigation on all patients. This approach is likely to be welcomed by patients and will lead to significant savings in terms of time and resources for patients and staff. Further larger studies are warranted to validate this selective approach in the diagnosis of CFRD.

In this resumed investigation, the effectiveness of manganese as an austenite-forming element in 17% and 20% chromium stainless steels has been investigated. The effect of manganese on the corrosion and mechanical properties of a range of experimental, low-cost, manganese-containing, dual-phase stainless steels is evaluated and reported.