Chemical speciation of neptunium(VI) under strongly alkaline conditions. Structure, composition, and oxo ligand exchange.

Hexavalent neptunium can be solubilized in 0.5-3.5 M aqueous MOH (M = Li(+), Na(+), NMe4(+) = TMA(+)) solutions. Single crystals were obtained from cooling of a dilute solution of Co(NH3)6Cl3 and NpO2(2+) in 3.5 M [N(Me)4]OH to 5 °C. A single-crystal X-ray diffraction study revealed the molecular formula of [Co(NH3)6]2[NpO2(OH)4]3·H2O, isostructural with the uranium analogue. The asymmetric unit contains three distinct NpO2(OH)4(2-) ions, each with pseudooctahedral coordination geometry with trans-oxo ligands. The average Np═O and Np-OH distances were determined to be 1.80(1) and 2.24(1) Å, respectively. EXAFS data and fits at the Np L(III)-edge on solid [Co(NH3)6]2[NpO2(OH)4]3·H2O and aqueous solutions of NpO2(2+) in 2.5 and 3.5 M (TMA)OH revealed bond lengths nearly identical with those determined by X-ray diffraction but with an increase in the number of equatorial ligands with increasing (TMA)OH concentration. Raman spectra of single crystals of [Co(NH3)6]2[NpO2(OH)4]3·H2O reveal a ν1(O═Np═O) symmetric stretch at 741 cm(-1). Raman spectra of NpO2(2+) recorded in a 0.6-2.2 M LiOH solution reveal a single ν1 frequency of 769 cm(-1). Facile exchange of the neptunyl oxo ligands with the water solvent was also observed with Raman spectroscopy performed with (16)O- and (18)O-enriched water solvent. The combination of EXAFS and Raman data suggests that NpO2(OH)4(2-) is the dominant solution species under the conditions of study and that a small amount of a second species, NpO2(OH)5(3-), may also be present at higher alkalinity. Crystal data for [Co(NH3)6]2[NpO2(OH)4]3·H2O: monoclinic, space group C2/c, a = 17.344(4) Å, b = 12.177(3) Å, c = 15.273 Å, ß = 120.17(2)°, Z = 4, R1 = 0.0359, wR2 = 0.0729.

There are calls for a national screening programme for prostate cancer: what is the evidence to justify such a national screening programme?

INTRODUCTION: Prostate cancer is the commonest cancer in men and a major health issue worldwide. Screening for early disease has been available for many years, but there is still no national screening programme established in the United Kingdom. OBJECTIVE: To assess the latest evidence regarding prostate cancer screening and whether it meets the necessary requirements to be established as a national programme for all men. METHODS: Electronic databases and library catalogues were searched electronically and manual retrieval was performed. Only primary research results were used for the analysis. RESULTS: In recent years, several important randomised controlled trials have produced varied outcomes. In Europe the largest study thus far concluded that screening reduced prostate cancer mortality by 20%. On the contrary, a large American trial found no reduction in mortality after 7-10 years follow-up. Most studies comment on the adverse effects of screening - principally those of overdiagnosis and subsequent overtreatment. DISCUSSION: Further information about the natural history of prostate cancer and accuracy of screening is needed before a screening programme can be truly justified. In the interim, doctors and patients should discuss the risks, benefits and sequelae of taking part in voluntary screening for prostate cancer.

Where have we come from and where are we going? The paediatric HIV programme in Johannesburg, South Africa, from 2004 to 2018: A retrospective analysis of programme trends.

BACKGROUND: The paediatric HIV treatment programme in South Africa (SA) has grown since its inception in 2004. Despite this impressive scale-up of antiretroviral therapy (ART) in children, the proportion of children started on ART and retained in care remains unacceptably low, with only 47% of the 340 000 HIV-positive children in SA on ART in 2020. Johannesburg is one of the districts in SA with the largest number of children living with HIV who are not on ART, and is a priority district for paediatric case finding and retention. OBJECTIVES: To describe the dynamics of the paediatric HIV programme in Johannesburg, SA. METHODS: A secondary analysis was conducted on patient-level HIV treatment data from TIER.Net, the nationally mandated HIV/ART database. Children aged <15 years who received ART between January 2004 and June 2019 at public health facilities in Johannesburg were included. We reported the number of children on ART and the number who entered and exited the programme by age group over time, and analysed the trends of these indicators. RESULTS: By December 2018, 7 630 children aged <15 years remained in Johannesburg's paediatric ART programme: 82.5% were aged 5 - <15 years, with 54.1% of these being 10 - <15 years old. During the study period, 19 850 children were newly initiated on ART. New initiations slowed from 2013, to range from 1 172 to 1 373 yearly. In 2018, 34.2% of initiators were aged <1 year, 24.2% 1 - <5 years and 41.6% 5 - <15 years. Despite these initiations, the number of children on ART only grew by 97 in 2018, owing to programme losses. In 2018, 924  children (12.1%) aged out, 35 (0.5%) died and 983 (12.9%) were lost to follow-up (LTFU), the latter having increased from 10.7% in 2017. Of children who aged out of the paediatric ART programme, 56.3% remained in care at the same facility. CONCLUSION: Early in the SA ART roll-out, many children were found to be HIV infected and started on ART. This number started to slow in 2013, after which the growth rate of the paediatric HIV programme also began to slow. Scale-up of methods for identifying older children with HIV is needed. While ageing out of the paediatric programme is a consideration, the number of children LTFU remains unacceptably high. Further interrogation of barriers to paediatric retention is needed to help realise the Joint United Nations Programme on HIV and AIDS (UNAIDS) 90:90:90 goals for children in SA.

Control of HIF-1{alpha} and vascular signaling in fetal lung involves cross talk between mTORC1 and the FGF-10/FGFR2b/Spry2 airway branching periodicity clock.

Lung development requires coordinated signaling between airway and vascular growth, but the link between these processes remains unclear. Mammalian target of rapamycin complex-1 (mTORC1) can amplify hypoxia-inducible factor-1α (HIF-1α) vasculogenic activity through an NH(2)-terminal mTOR binding (TOS) motif. We hypothesized that this mechanism coordinates vasculogenesis with the fibroblast growth factor (FGF)-10/FGF-receptor2b/Spry2 regulator of airway branching. First, we tested if the HIF-1α TOS motif participated in epithelial-mesenchymal vascular signaling. mTORC1 activation by insulin significantly amplified HIF-1α activity at fetal Po(2) (23 mmHg) in human bronchial epithelium (16HBE14o-) and induced vascular traits (Flk1, sprouting) in cocultured human embryonic lung mesenchyme (HEL-12469). This enhanced activation of HIF-1α by mTORC1 was abolished on expression of a HIF-1α (F99A) TOS-mutant and also suppressed vascular differentiation of HEL-12469 cocultures. Next, we determined if vasculogenesis in fetal lung involved regulation of mTORC1 by the FGF-10/FGFR2b/Spry2 pathway. Fetal airway epithelium displayed distinct mTORC1 activity in situ, and its hyperactivation by TSC1(-/-) knockout induced widespread VEGF expression and disaggregation of Tie2-positive vascular bundles. FGF-10-coated beads grafted into fetal lung explants from Tie2-LacZ transgenic mice induced localized vascular differentiation in the peripheral mesenchyme. In rat fetal distal lung epithelial (FDLE) cells cultured at fetal Po(2), FGF-10 induced mTORC1 and amplified HIF-1α activity and VEGF secretion without induction of ERK1/2. This was accompanied by the formation of a complex between Spry2, the cCBL ubiquitin ligase, and the mTOR repressor, TSC2, which abolished GTPase activity directed against Rheb, the G protein inducer of mTORC1. Thus, mTORC1 links HIF-1α-driven vasculogenesis with the FGF-10/FGFR2b/Spry2 airway branching periodicity regulator.

FEIBA prophylaxis in haemophilia patients: a clinical update and treatment recommendations.

In patients with severe haemophilia and inhibitors, regular factor VIII inhibitor bypassing activity (FEIBA) prophylaxis has been shown to reduce the frequency of bleeding by up to 85% and to improve patient quality of life. FEIBA is well tolerated; the incidence of thrombotic events and of allergic reactions is extremely low. The concept of prophylaxis in haemophilia patients with inhibitors is relatively new and some clinicians may be unsure of how to use FEIBA in this context. These treatment recommendations, based on published evidence plus the collective experience of a group of haematologists (with practical knowledge of managing inhibitor patients with FEIBA prophylaxis), are intended to provide guidance to clinicians considering initiating and maintaining patients on FEIBA prophylaxis with specific focus on practical aspects of patient selection, dosing, monitoring and stop criteria.

Guideline on the selection and use of therapeutic products to treat haemophilia and other hereditary bleeding disorders. A United Kingdom Haemophilia Center Doctors' Organisation (UKHCDO) guideline approved by the British Committee for Standards in Haematology.

Evidence-based guidelines are presented on the selection and use of therapeutic products to treat haemophilia and other hereditary bleeding disorders. They include details of therapeutic products available in the UK and they update and replace previous United Kingdom Haemophilia Centre Doctors' Organisation guidelines.

Estimated glomerular filtration rate is unreliable in detecting renal function loss during follow-up after cystectomy and urinary diversion.

PURPOSE: To evaluate the accuracy of estimated glomerular filtration rate (eGFR) against the reference standard of isotopic GFR (iGFR) in monitoring renal function during follow-up after cystectomy and urinary diversion. METHODS: Patients who had undergone cystectomy and ileal conduit urinary diversion at two centres between August 2001 and August 2006 were identified. eGFR calculated using the MDRD formula was compared to (51)Cr EDTA measured iGFR values measured at similar time-points during follow-up. RESULTS: Six hundred and fourteen paired iGFR and eGFR results were analysed from 166 patients (18% female, median age 70 years). There was a significant difference between paired iGFR and eGFR measurements (p < 0.0001) with a mean bias of +1.8 mls/min/1.73 m(2) (SD 18.0) and a 95% limit of agreement of -33.5 to 37.2 mls/min/1.73 m(2). iGFR and eGFR values converged at a GFR of approximately 45 mls/min/1.73 m(2). 70.6% of patients experienced a loss of renal function greater than expected (>0.58 mls/min/1.73 m(2)/year). In 22.4% of these patients, a decline of greater than 10% in iGFR occurred that was undetected by eGFR measurements, which overestimated GFR. There was no significant relationship between patient height, weight or body mass index and the accuracy of eGFR measurements. CONCLUSIONS: iGFR measurement is recommended following ileal conduit urinary diversion if early signs of renal function loss are to be detected. eGFR overestimates GFR in critically relevant ranges and fails to detect loss in a clinically significant proportion of patients.

Weakened anterior roots--intraradicular rehabilitation.

This paper highlights the fact that many anterior teeth requiring restoration are severely weakened having wide, flared canal spaces, and thin dentinal walls that are prone to fracture. Traditionally these teeth have been restored using metal posts and are often unsuccessful because of lack of retention or root fracture. This paper describes how mineral trioxide aggregate (MTA) can be used to form an immediate apical seal rather than waiting months for apexification. Weakened roots can be reinforced using dentine bonding agents and composite resin and if insufficient coronal tooth structure is present a quartz-fibre post can be placed to retain a composite core.

Restoration of the root-filled tooth: pre-operative assessment.

This is the first in a series of four papers related to the management of root canal treated teeth. When teeth compromised by extensive restorations become non-vital, suggestions have been given as to how root canal treatment can be carried out with the greatest chance of success. Once root canal treated, either by a previous dentist or by the current dentist, a review of the assessment process that should be carried out prior to placing costly indirect definitive restorations is given. It will be clear that post-retained restorations are mainly reserved for anterior or single-rooted teeth, posterior teeth rarely requiring a post for core retention. The second paper in this series describes the basic tooth preparation that should be carried out prior to placing a post. Depending on the type of post system used, further modifications to tooth preparation may be required and the cementation techniques may also have to be modified. The third paper therefore discusses the various post types, when and how they should be used for optimum results. The final paper addresses reinforcement and restoration of compromised root canals, such as those with immature, open apices, or those that have been over-prepared for previous post-retained restorations.

Tooth preparation for post-retained restorations.

Failure of root canal treatment and/or post crowns can be avoided in many cases if appropriate tooth preparation is carried out. This paper discusses the rationale for the timing of post placement following root canal treatment and appropriate methods for removal of gutta-percha prior to post space preparation. The basic principles of post space preparation are described, which should reduce the risk of weakening the root unnecessarily, causing damage to the periodontium and post perforation.

Post and core systems, refinements to tooth preparation and cementation.

With a plethora of post systems available, it is often difficult to decide which one to use. This is made more difficult by the fact that new posts are introduced before existing ones are fully evaluated in laboratory and clinical studies. This paper therefore describes the different post types and the main advantages and disadvantages of each. In addition, the choice of post system will influence whether further tooth preparation is required and will dictate which luting cement and core material are most appropriate. Whilst the choice of post will, for many dentists, be driven by personal preference and a history of clinical success, there are certain pit falls to avoid and these are outlined.

The application of acoustic impedance measurements to pediatric clinical practice.

This article provides background information on acoustic impedance testing and illustrates utilization of test results in pediatric clinical practice. Acoustic impedance measurement devices are presently being used successfully by hearing screening programs and by otorhinolaryngologists in clinical and hospital settings. As a diagnostic tool, the acoustic impedance bridge can have particular applicability in dealing withe young children and other difficult-to-test populations. Impedance measurements can provide physicians with objective information about the condition of the middle ear, oftentimes more accurately than either otoscopic examination or standard audiometry. The technique described can assist physicians in diagnosing middle-ear diseases and in monitoring the effects of otological treatment.

An evaluation of near-patient testing for Helicobacter pylori in general practice.

INTRODUCTION: A knowledge of Helicobacter pylori status is likely to be important in the management of patients presenting in general practice with dyspepsia. Near-patient testing kits for the detection of the H. pylori antibodies in whole blood, which provide results very quickly, are now available. AIM: To determine the test characteristics of the Helisal Rapid Blood test in general practice and to describe the ways in which general practitioners incorporate the results of H. pylori testing into their management of patients with dyspepsia. SETTING: Nine general practices in the United Kingdom. PATIENTS: Consecutive patients presenting with dyspepsia in whom further investigation or referral was considered. METHODS: A whole blood fingerstick sample was tested for H. pylori antibodies using the Helisal Rapid Blood test and a venous sample was obtained for subsequent laboratory testing using Helisal Serum and Helico G (ELISA) methods. Results of the three tests were compared and analysed. Clinical data were recorded by the general practitioners. RESULTS: Full serological data were obtained on 123 patients, mean age 44.8 years. The sensitivity and specificity of the Helisal Rapid Blood test, compared with concordant results of the laboratory tests, were 83% and 78%, respectively. The prevalence of H. pylori-positive patients was 57%, with a positive predictive value of 83% and a negative predictive value of 78%. The results of the test had a significant impact on the clinical management of the patients in the study. COMMENT: The Helisal Rapid Blood test is a useful and convenient method of improving the clinical care of patients with dyspepsia in general practice.

Analysis of the effector functions of different populations of mucosal lymphocytes.

Lymphocytes separated from the epithelial layer of mouse small intestine, IEL, were tested for their NK cytotoxicity against Yac-1 targets. There was little NK activity in a 4 hour assay, but high activity in an 18 hour assay, and the NK activity of IEL did not parallel that in the spleen in any of the mouse strains tested. Furthermore, IEL exerted a suppressor activity on mouse spleen NK activity. Specific T-cell cytotoxicity appeared in IEL in mice immunized with an intraperitoneal injection of P-815 tumor cells. By contrast with IEL, LPL had little NK or NK suppressor activity, but higher levels of specific T-cell cytotoxicity in tumor-immunized mice than intraepithelial lymphocytes. A high proportion of IEL had granules that stained with Giemsa and Astra blue. Furthermore many IEL carried Lyt-2+ phenotype and no other T-cell surface antigen. Intraepithelial lymphocytes appeared, therefore, to have staining and phenotype characteristics of both granular NK cells and suppressor cells. It was clear that the intestinal mucosa contained populations of immune effector cells that were heterogeneous in nature and function.

A Raman spectroscopic study of arsenite and thioarsenite species in aqueous solution at 25°C.

The Raman spectra of thioarsenite and arsenite species in aqueous solution were obtained at room temperature. Solutions at constant ΣAs + ΣS of 0.1 and 0.5 mol kg-1 were prepared with various ΣS/ΣAs ratios (0.1-9.0) and pH values (~7-13.2). Our data suggest that the speciation of As under the conditions investigated is more complicated than previously thought. The Raman measurements offer evidence for at least six separate S-bearing As species whose principal bands are centered near 365, 385, 390, 400, 415 and 420 cm-1. The data suggest that at least two different species may give rise to bands at 385 cm-1, bringing the probable minimum number of species to seven. Several additional species are possible but could not be resolved definitively. In general, the relative proportions of these species are dependent on total As concentration, ΣS/ΣAs ratio and pH. At very low ΣS/ΣAs ratios we also observe Raman bands attributable to the dissociation products of H3AsO3(aq). Although we were unable to assign precise stoichiometries for the various thioarsenite species, we were able to map out general pH and ΣS/ΣAs conditions under which the various thioarsenite and arsenite species are predominant. This study provides a basis for more detailed Raman spectroscopic and other types of investigations of the nature of thioarsenite species.

Measurement of 51Co-vitamin B12 uptake using a static wholebody counter.

Using a whole-body counter which incorporates eight static NaI((Tl) detectors, it has been found possible to measure the absorption of vitamin B12 labelled with 57Co instead of 58Co, with a consequent reduction in absorbed radiation dose to the patient.

Randomised controlled trial of reminders to enhance the impact of audit in general practice on management of patients who use benzodiazepines.

OBJECTIVE: To determine whether reminder cards in medical records enhance the effectiveness of audit with feedback in improving the care of patients taking long term benzodiazepine drugs. DESIGN: Randomised trial, practices receiving feedback only in one group and practices receiving feedback plus reminder cards in the other group. SETTING: 18 general practices in Leicestershire. SUBJECTS: Random samples of patients who had been taking a benzodiazepine anxiolytic or hypnotic drug for four weeks or longer. MAIN OUTCOME MEASURES: Entries in medical records indicating compliance with five criteria of care: assessment of suitability for withdrawal; being told about dependency; withdrawal being recommended; withdrawal or continuing medication; and a consultation with the general practitioner in the past year. Data were collected before and after feedback or feedback plus reminders. RESULTS: Of a total population of 125,846 registered with the 18 practices, 2409 (1.9%) had been taking a benzodiazepine for four weeks or longer. Of the 742 in the first samples, 543 (73.2%) were women, the mean (SD) age was 68.7 (14.9) years, and they had been taking a benzodiazepine for 10.1 (6.7) years. The number of patients whose care complied with the criteria rose after the interventions to implement change. The increase was greater in practices receiving feedback plus reminders for only two of the five criteria "told about dependency" increasing from 52 (11.1%) to 118 (25.8%) in the feedback only group, and from 27 (10.5%) to 184 (43.0%) in the feedback plus reminders group; odds ratio (OR) 1.46 (95% confidence interval (95% CI) 1.32 to 5.21); and "consulted in the past year" increasing from 434 (93.1%) to 411 (95.8%) in the feedback only group and 255 (96.6%) to 400 (99.8%) in the feedback plus reminders group, OR (95% CI) 13.5 (2.01 to 330.3). CONCLUSIONS: Reminder cards had only a limited effect and cannot be recommended for routine use. There were improvements in the care of patients of both groups of practices and further studies are indicated to determine the impact of both systematically developed criteria and reminders embedded into restructured medical records.

Effects of the inclusion of yeast culture (Saccharomyces cerevisiae plus growth medium) in the diet of dairy cows on milk yield and forage degradation and fermentation patterns in the rumen of steers.

The effects of including yeast culture (YC; Saccharomyces cerevisae plus growth medium; 5 x 10(9) organisms/g) in diets for ruminants was examined in two experiments. In Exp. 1, 32 multiparous Friesian dairy cows were fed between wk 7 to 12 of lactation one of four completely mixed diets based on either hay or straw plus rolled barley (mixed to give concentrate:forage ratios of either 50:50 or 60:40, respectively) with or without 10 g YC/d in a 2(3) factorial design. Supplementation with YC increased DM intake of the cows by a mean of 1.2 kg/d (P less than or equal to .062) and increased milk yield by 1.4 liters/d (corrected to 4% butterfat; P less than or equal to .05). There was an interaction (P less than .05) between diet composition and YC addition; effects of YC were greatest in diets containing 60:40 (concentrate:forage) ratio. In Exp. 2, three steers were fed a diet of 50% hay and 50% rolled barley (DM basis). Hay was available for the major part of the day but barley was fed in two meals/d. Addition of YC to the diet increased (P less than .05) ruminal pH for 4 h after the barley meal. This elevation in pH probably was due to a reduction (P less than or equal to .01) in the concentration of L-lactate in the ruminal liquor of steers given YC (1.43 vs 3.55 mM; P less than or equal to .01). Peak ruminal L-lactate concentration (7.75 mM) in the controls coincided with time of minimum pH values (2 h after the meal of barley); this peak was absent in steers given YC. YC had no effect on the concentration of VFA in ruminal liquor, but the ratio of acetate to propionate was reduced (P less than or equal to .01) from 3.3:1 to 2.8:1 in steers given YC. The extent of DM degradation of hay incubated in the rumen of steers fed the hay and rolled barley diet was increased (P less than .05) in the presence of YC at 12 h of incubation, but degradation was similar in all treatment groups after 24 h of incubation. Presence of yeast culture in the rumen had effects on ruminal stoichiometry. An increased rate of forage degradation may have increased forage intake and productivity of these dairy cows.

Limiting the use of gastrointestinal decontamination does not worsen the outcome from deliberate self-poisoning.

AIM: To review the current epidemiology of patients with deliberate self-poisoning presenting to Christchurch Emergency Department, and to compare this with 1996, 1992, and 1989 data. METHODS: A retrospective analysis of computer and case records over the twelve-month period of 1999 was conducted and compared with published data from 1996,1992 and 1989. RESULTS: There were 561 presentations of deliberate self-poisoning to Christchurch Hospital, representing 0.87% of total presentations (compared with 1.1% in 1996, 1.2% in 1992, and 1.0% in 1989). The female to male ratio was 2.2:1.0 (compared with 1.9:1.0, 1.5:1.0, and 2.1:1.0). The principal drugs ingested were antidepressants 30.8% (compared with 20.1%, 24.4%,15.7%), paracetamol 23.5% (compared with 16.7%, 16.9%, 10.6%), benzodiazepines 23.0% (compared with 11.1%, 23.6% 22.8%) and antipsychotics 17.8% (compared with 10.7%, 16.1%, not reported). Gastrointestinal decontamination was performed in only 14.4% of patients (compared with 61%, 73%, 61%). Activated charcoal was given alone in 13.2% (compared with 54%, 46%, 0.4%), activated charcoal and gastric lavage in 0.7% (7%, 26%, 53%), a whole bowel irrigation in 0.5% (not recorded in previous papers). 70.4% were admitted (compared with 69%, 59%, 64%), 7% to intensive care (10.2%, 10.6%, 18%). There were two deaths (compared with 6, 2 and 2). CONCLUSIONS: Over the time periods studied the drugs ingested and admission rates remain similar, although a large proportion are now being observed in the emergency short stay ward, reducing admission rates to the ward and intensive care. Trends in gastrointestinal decontamination have changed dramatically over the four time periods, but there has been no worsening in the outcome of patients with deliberate self-poisoning.

Effectiveness of three root canal medicaments to eliminate Actinomyces israelii from infected dentinal tubules in vitro.

The persistence of anaerobic bacteria in the root canal system often leads to treatment failure. One possible reason for this may be the retention of micro-organisms in the dentinal tubules of root canal walls. This study was performed to compare the effectiveness of two root canal medicaments and a chlorhexidine solution in disinfecting Actinomyces israelii-infected root canal walls and dentinal tubules in vitro. Dentinal tubules of root canal walls of human teeth were experimentally infected with A. israelii. The root canals were exposed to either iodine potassium iodide, calcium hydroxide or 2% chlorhexidine for periods of 3, 7 and 60 days. At the end of the medication periods samples were removed at different depths and tested for A. israelii viability. Chlorhexidine was the only disinfectant that was able to eliminate A. israelii from all the samples after 3, 7 as well as 60 days while 25% of the specimens treated with iodine potassium iodide and 50% of the specimens treated with calcium hydroxide still had viable A. israelii after treatment. It is clear from this study that 2% chlorhexidine is superior to iodine potassium iodide and calcium hydroxide in its ability to remove A. israelii from infected dentinal tubules. However, in vivo trials need to be undertaken before its clinical use can be recommended.