MR-guided HDR prostate brachytherapy with teleoperated steerable needles.

Conformity of tumour volumes and dose plans in prostate brachytherapy (BT) can be constrained by unwanted needle deflections, needle access restrictions and visualisation limitations. This work validates the feasibility of teleoperated robotic control of an active steerable needle using magnetic resonance (MR) for guidance. With this system, perturbations can be counteracted and critical structures can be circumvented to access currently inaccessible areas. The system comprises of (1) a novel steerable needle, (2) the minimally invasive robotics in an MR environment (MIRIAM) system, and (3) the daVinci Research Kit (dVRK). MR scans provide visual feedback to the operator controlling the dVRK. Needle steering is performed along curved trajectories to avoid the urethra towards targets (representing tumour tissue) in a prostate phantom with a targeting error of 1.2 ± 1.0 mm. This work shows the potential clinical applicability of active needle steering for prostate BT with a teleoperated robotic system in an MR environment.

Axially rigid steerable needle with compliant active tip control.

Steerable instruments allow for precise access to deeply-seated targets while sparing sensitive tissues and avoiding anatomical structures. In this study we present a novel omnidirectional steerable instrument for prostate high-dose-rate (HDR) brachytherapy (BT). The instrument utilizes a needle with internal compliant mechanism, which enables distal tip steering through proximal instrument bending while retaining high axial and flexural rigidity. Finite element analysis evaluated the design and the prototype was validated in experiments involving tissue simulants and ex-vivo bovine tissue. Ultrasound (US) images were used to provide visualization and shape-reconstruction of the instrument during the insertions. In the experiments lateral tip steering up to 20 mm was found. Manually controlled active needle tip steering in inhomogeneous tissue simulants and ex-vivo tissue resulted in mean targeting errors of 1.4 mm and 2 mm in 3D position, respectively. The experiments show that steering response of the instrument is history-independent. The results indicate that the endpoint accuracy of the steerable instrument is similar to that of the conventional rigid HDR BT needle while adding the ability to steer along curved paths. Due to the design of the steerable needle sufficient axial and flexural rigidity is preserved to enable puncturing and path control within various heterogeneous tissues. The developed instrument has the potential to overcome problems currently unavoidable with conventional instruments, such as pubic arch interference in HDR BT, without major changes to the clinical workflow.

Comment on: "A novel approach to peatlands as archives of total cumulative spatial pollution loads from atmospheric deposition of airborne elements complementary to EMEP data: Priority pollutants (Pb, Cd, Hg)" by Ewa Miszczak, Sebastian Stefaniak, Adam Michczynski, Eiliv Steinnes and Irena Twardowska.

A recent paper by Miszczak et al. (2020) examines metal contamination of mires in Poland and Norway. The authors conclude that lead (Pb) records in ombrotrophic peatlands cannot be used to reconstruct the chronological history of anthropogenic activities due to post-depositional mobility of the metal. We contest this general conclusion which stands in contrast with a significant body of literature demonstrating that Pb is largely immobile in the vast majority of ombrotrophic peatlands. Our aim is to reaffirm the crucial contribution that peat records have made to our knowledge of atmospheric Pb contamination. In addition, we reiterate the necessity of following established protocols to produce reliable records of anthropogenic Pb contamination in environmental archives.

Alignment in total knee replacement.

The advent of computer-assisted knee replacement surgery has focused interest on the alignment of the components. However, there is confusion at times between the alignment of the limb as a whole and that of the components. The interaction between them is discussed in this article. Alignment is expressed relative to some reference axis or plane and measurements will vary depending on what is selected as the reference. The validity of different reference axes is discussed. Varying prosthetic alignment has direct implications for surrounding soft-tissue tension. In this context the interaction between alignment and soft-tissue balance is explored and the current knowledge of the relationship between alignment and outcome is summarised.

Computer-assisted total knee replacement. A controlled cadaver study using a multi-parameter quantitative CT assessment of alignment (the Perth CT Protocol).

A controlled study, comparing computer- and conventional jig-assisted total knee replacement in six cadavers is presented. In order to provide a quantitative assessment of the alignment of the replacements, a CT-based technique which measures seven parameters of alignment has been devised and used. In this a multi-slice CT machine scanned in 2.5 mm slices from the acetabular roof to the dome of the talus with the subject's legs held in a standard position. The mechanical and anatomical axes were identified, from three-dimensional landmarks, in both anteroposterior and lateral planes. The coronal and sagittal alignment of the prosthesis was then measured against the axes. The rotation of the femoral component was measured relative to the transepicondylar axis. The rotation of the tibial component was measured with reference to the posterior tibial condyles and the tibial tuberosity. Coupled femorotibial rotational alignment was assessed by superimposition of the femoral and tibial axial images. The radiation dose was 2.7 mSV. The computer-assisted total knee replacements showed better alignment in rotation and flexion of the femoral component, the posterior slope of the tibial component and in the matching of the femoral and tibial components in rotation. Differences were statistically significant and of a magnitude that support extension of computer assistance to the clinical situation.

Computer-assisted revision total knee replacement.

A technique for performing allograft-augmented revision total knee replacement (TKR) using computer assistance is described, on the basis of the results in 14 patients. Bone deficits were made up with impaction grafting. Femoral grafting was made possible by the construction of a retaining wall or dam which allowed pressurisation and retention of the graft. Tibial grafting used a mixture of corticocancellous and morsellised allograft. The position of the implants was monitored by the computer system and adjusted while the cement was setting. The outcome was determined using a six-parameter, quantitative technique (the Perth CT protocol) which measured the alignment of the prosthesis and provided an objective score. The final outcomes were not perfect with errors being made in femoral rotation and in producing a mismatch between the femoral and tibial components. In spite of the shortcomings the alignments were comparable in accuracy with those after primary TKR. Computer assistance shows considerable promise in producing accurate alignment in revision TKR with bone deficits.

Support for breastfeeding mothers.

BACKGROUND: Both observational and recent experimental evidence support the promotion of breastfeeding as the optimal form of infant nutrition. There is, however, uncertainty as to the most effective way of providing support to women who choose to breastfeed their children. A systematic review was performed to describe studies undertaken in this area and to assess the effectiveness of supplementary support. OBJECTIVES: The objective of this review was to assess the effects of breastfeeding support. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register, MEDLINE and EMBASE. These were last searched in March 2001. Secondary references were searched and researchers in the field were contacted. SELECTION CRITERIA: Controlled trials of acceptable quality comparing extra support for breastfeeding mothers with usual maternity care. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and checked by a second reviewer. MAIN RESULTS: Twenty eligible randomised or quasi-randomised controlled trials from 10 countries were identified involving 23,712 mother-infant pairs. There was a beneficial effect on the duration of any breastfeeding in the meta-analysis of all forms of extra support (relative risk (RR) for stopping any breastfeeding before six months 0.88 [95% confidence interval (CI) 0.81,0.95]; 15 trials, 21,910 women). The effect was greater for exclusive breastfeeding (RR 0.78 [95% CI 0.69,0.89]; 11 trials, 20,788 women). Extra professional support appeared beneficial for any breastfeeding (RR 0.89 [95% CI 0.81,0.97]; 10 trials, 19,696 women) and for exclusive breastfeeding (RR 0.90 [95% confidence interval 0.81,1.01]; six trials, 18,258 women) although the latter effect did not achieve full statistical significance. Lay support was effective in reducing the cessation of exclusive breastfeeding (RR 0.66 [95% CI 0.49,0.89]; five trials, 2530 women) but its effect on any breastfeeding did not reach statistical significance (RR 0.84 [95% CI 0.69,1.02]; five trials, 2224 women). Professional support in the largest trial to assess health outcomes produced a significant reduction in the risk of gastro-intestinal infections and atopic eczema. In two trials with children suffering from diarrhoeal illness extra support was highly effective in increasing short term exclusive breastfeeding rates and reducing recurrence of diarrhoea. REVIEWER'S CONCLUSIONS: Consideration should be given to providing supplementary breastfeeding support as part of routine health service provision. There is clear evidence for the effectiveness of professional support on the duration of any breastfeeding although the strength of its effect on the rate of exclusive breastfeeding is uncertain. Lay support is effective in promoting exclusive breastfeeding while the strength of its effect on the duration of any breastfeeding is also uncertain. Evidence supports the promotion of exclusive breastfeeding as central to the management of diarrhoeal illness in partially breastfed infants. Further trials are required to assess the effectiveness (including cost-effectiveness) of both lay and professional support in different settings - in particular in those communities with low rates of breastfeeding initiation. Research is also required into the most appropriate training for those, whether lay or professional, who support breastfeeding mothers.

Pseudomonas kilonensis sp. nov., a bacterium isolated from agricultural soil.

A total of 131 bacterial isolates related to Pseudomonas corrugata were obtained from an agricultural soil from northern Germany. Based on 16S rRNA gene sequences, PCR-based genome fingerprinting and multilocus enzyme electrophoresis, they formed two groups, A (119 strains) and B (12 strains). As members of each group were highly similar, a single strain of each group was subsequently characterized by a polyphasic taxonomic approach. The selected member of group A was identified as a strain of Pseudomonas brassicacearum, whereas the selected member of group B was distinct from other species of the genus Pseudomonas. Although DNA-DNA hybridization suggested a close affiliation of the group B strain with P. brassicacearum and Pseudomonas thivervalensis and ribotyping suggested a close affiliation with P. brassicacearum, RAPD data, 16S rRNA gene sequencing and phenotypic characterization indicated the presence of a distinct taxonomic entity. This strain differed from the type strains of P. thivervalensis and P. brassicacearum in 10 and 12 metabolic properties, respectively, whereas the two organisms differ from one another by only two properties. Strains of group B are therefore considered to be members of a new species, for which the name Pseudomonas kilonensis sp. nov. is proposed. The type strain is strain 520-20T (= DSM 13647T = CFBP 5372T).

Novel heteroaryl replacements of aromatic 3-tetrafluoroethoxy substituents in trifluoro-3-(tertiaryamino)-2-propanols as potent inhibitors of cholesteryl ester transfer protein.

A series of novel N,N-disubstituted trifluoro-3-amino-2-propanols has been prepared as potent inhibitors of cholesteryl ester transfer protein (CETP). Modifying the aromatic 3-tetrafluoroethoxy group in the lead molecule 1a with various heteroaryl moieties produced new 2-furyl analogues 2a,b with submicromolar potency in vitro.

Prevalence of breastfeeding at four months in general practices in south London.

BACKGROUND: Successive quinquennial National Infant Feeding Surveys have provided a valuable picture of national and regional variations in infant feeding practices within the United Kingdom. Social variation in breastfeeding has been recognised to be an important source of health inequalities in childhood by the Independent Inquiry into Inequalities in Health Report. AIM: To determine the prevalence of breastfeeding at birth and at four months in a sample of women from urban general practices, its variation between practices, and relation to practice population deprivation scores. To report the timing of introduction of solid feeds. DESIGN OF STUDY: Cross-sectional questionnaire survey based on a random cluster sample. SETTING: Women with infants aged four months in general practices in South London. METHOD: Mode of infant feeding at birth and four months, and time of introduction of solids. Jarman score as a measure of practice population deprivation. Housing tenure, maternal ethnic group, and maternal age at leaving full-time education. RESULTS: Twenty-five general practices were sampled. Median practice Jarman score was 15.0 (interquartile range [IQR] = 12.6-21.9). Responses were received from 1053 out of 1532 mothers approached (69%). Of these, 87% (897) had breastfed at birth, while 59% (609) were still breastfeeding their babies at four months. Mothers in rented accommodation were less likely to breastfeed than owner-occupiers (odds ratio [95% CI] = 0.52 [0.37-0.74]), as were women of white, compared with those of black, ethnic origin (odds ratio [95% CI] = 0.55 [0.36-0.82]). Those who completed up to two years and more than two years education after the age of 16 were 2.94 (95% CI = 1.85-4.66) and 9.25 (95% CI = 6.02-14.21) more likely to breastfeed at four months, respectively, than mothers whose formal education was completed at or before 16 years. Practice-specific rates of breastfeeding ranged from 71% to 100% at birth (median 87%; IQR = 79-93%) and 22% to 83% at four months (median 61%; interquartile range = 47-66%). The intra-practice correlation coefficient for breastfeeding at four months was 0.052 (within-cluster variance = 0.23, between-cluster variance = 0.013). There was no association between breastfeeding at four months and practice-specific Jarman score. Median age of starting solids was 16 weeks (IQR = 15-17 weeks). CONCLUSIONS: Housing tenure, maternal education, and ethnic group are significantly associated with breastfeeding prevalence at four months. Between-practice variation in breastfeeding prevalence is not associated with measures of practice population deprivation, as assessed by Jarman scores. Consideration should be given to including information on maternal ethnic group and housing tenure in future National Infant Feeding Surveys. Current weaning practices fall short of the recommendation of the World Health Assembly.

The structure of a local population of phytopathogenic Pseudomonas brassicacearum from agricultural soil indicates development under purifying selection pressure.

Among the isolates of a bacterial community from a soil sample taken from an agricultural plot in northern Germany, a population consisting of 119 strains was obtained that was identified by 16S rDNA sequencing and genomic fingerprinting as belonging to the recently described species Pseudomonas brassicacearum. Analysis of the population structure by allozyme electrophoresis (11 loci) and random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR; four primers) showed higher resolution with the latter method. Both methods indicated the presence of three lineages, one of which dominated strongly. Stochastic tests derived from the neutral theory of evolution (including Slatkin's exact test, Watterson's homozygosity test and the Tajima test) indicated that the population had developed under strong purifying selection pressure. The presence of strains clearly divergent from the majority of the population can be explained by in situ evolution or by influx of strains as a result of migration or both. Phytopathogenicity of a P. brassicacearum strain determined with tomato plants reached the level obtained with the type strain of the known pathogen Pseudomonas corrugata. The results show that a selective sweep was identified in a local population. Previously, a local selective sweep had not been seen in several populations of different bacterial species from a variety of environmental habitats.

The discovery of new cholesteryl ester transfer protein inhibitors.

Cholesteryl ester transfer protein (CETP) has been an important but controversial target for elevating HDLc (high density lipoprotein cholesterol) and treating atherosclerosis. Significant progress toward inhibiting CETP has occurred on several fronts, including the development of an antisense inhibitor, irreversible small molecule inhibitors and reversible small molecule inhibitors. Several orally bioavailable, small molecule CETP inhibitors have shown potential to improve the HDLc to LDLc (low density lipoprotein cholesterol) ratio in various animal models at reasonable doses, and one of these compounds has shown efficacy in preventing atherosclerosis in a rabbit model. However, several more years of clinical testing will likely be needed to demonstrate that these clinical candidates can provide a potential therapeutic benefit to patients with coronary artery disease.

Stereospecific inhibition of CETP by chiral N,N-disubstituted trifluoro-3-amino-2-propanols.

Chiral N,N-disubstituted trifluoro-3-amino-2-propanols represent a recently discovered class of compounds that inhibit the neutral lipid transfer activity of cholesteryl ester transfer protein (CETP). These compounds all contain a single chiral center that is essential for inhibitory activity. (R,S)SC-744, which is composed of a mixture of the two enantiomers, inhibits CETP-mediated transfer of [(3)H]cholesteryl ester ([(3)H]CE) from HDL donor particles to LDL acceptor particles with an IC(50) = 200 nM when assayed using a reconstituted system in buffer and with an IC(50) = 6 microM when assayed in plasma. Upon isolation of the enantiomers, it was found that the (R,+) enantiomer, SC-795, was about 10-fold more potent than the mixture, and that the (S,-) enantiomer, SC-794, did not have significant inhibitory activity (IC(50) > 0.8 microM). All of the activity of the (S,-)SC-794 enantiomer could be accounted for by contamination of this sample with a residual 2% of the highly potent (R,+) enantiomer, SC-795. The IC(50) of (R,+)SC-795, 20 nM, approached the concentration of CETP (8 nM) in the buffer assay. These chiral N,N-disubstituted trifluoro-3-amino-2-propanols were found to associate with both LDL and HDL, but did not disrupt overall lipoprotein structure. They did not affect the on or off rates of CETP binding to HDL disk particles. Inhibition was highly specific since the activities of phospholipid transfer protein and lecithin cholesterol acyl transferase were not affected. Competition experiments showed that the more potent enantiomer (R)SC-795 prevented cholesteryl ester binding to CETP, and direct binding experiments demonstrated that this inhibitor bound to CETP with high affinity and specificity. It is estimated, based on the relative concentrations of inhibitor and lipid in the transfer assay, that (R)SC-795 binds approximately 5000-fold more efficiently to CETP than the natural ligand, cholesteryl ester. We conclude that these chiral N,N-disubstituted trifluoro-3-amino-2-propanol compounds do not affect lipoprotein structure or CETP-lipoprotein recognition, but inhibit lipid transfer by binding to CETP reversibly and stereospecifically at a site that competes with neutral lipid binding.