Strong Evidence for

The boundaries of the chart of nuclides contain exotic isotopes that possess extreme proton-to-neutron asymmetries. Here we report on strong evidence of ^{9}N, one of the most exotic proton-rich isotopes where more than one half of its constitute nucleons are unbound. With seven protons and two neutrons, this extremely proton-rich system would represent the first-known example of a ground-state five-proton emitter. The invariant-mass spectrum of its decay products can be fit with two peaks whose energies are consistent with the theoretical predictions of an open-quantum-system approach; however, we cannot rule out the possibility that only a single resonancelike peak is present in the spectrum.

Dissipative Reactions with Intermediate-Energy Beams: A Novel Approach to Populate Complex-Structure States in Rare Isotopes.

A novel pathway for the formation of multiparticle-multihole excited states in rare isotopes is reported from highly energy- and momentum-dissipative inelastic-scattering events measured in reactions of an intermediate-energy beam of ^{38}Ca on a Be target. The negative-parity, complex-structure final states in ^{38}Ca are observed following the in-beam γ-ray spectroscopy of events in the ^{9}Be(^{38}Ca,^{38}Ca+γ)X reaction in which the scattered projectile loses longitudinal momentum of order Δp_{||}=700 MeV/c. The characteristics of the observed final states are discussed and found to be consistent with the formation of excited states involving the rearrangement of multiple nucleons in a single, highly energetic projectile-target collision. Unlike the far-less-dissipative, surface-grazing reactions usually exploited for the in-beam γ-ray spectroscopy of rare isotopes, these more energetic collisions appear to offer a practical pathway to nuclear-structure studies of more complex multiparticle configurations in rare isotopes-final states conventionally thought to be out of reach with high-luminosity fast-beam-induced reactions.

Evaluation of immunogenicity and reactogenicity of COVID-19 vaccines in pregnant women.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with increased risk of adverse maternal and perinatal outcomes. Vaccines are highly effective at preventing severe coronavirus disease 2019 (COVID-19), but there are limited data on COVID-19 vaccines in pregnancy. This study aimed to investigate the reactogenicity and immunogenicity of COVID-19 vaccines in pregnant women when administered according to the 12-week-interval dosing schedule recommended in the UK. METHODS: This was a cohort study of pregnant women receiving COVID-19 vaccination between April and September 2021. The outcomes were immunogenicity and reactogenicity after COVID-19 vaccination. Pregnant women were recruited by phone, e-mail and/or text and were vaccinated according to vaccine availability at their local vaccination center. For immunogenicity assessment, blood samples were taken at specific timepoints after each dose to evaluate nucleocapsid protein (N) and spike protein (S) antibody titers. The comparator group comprised non-pregnant female healthcare workers in the same age group who were vaccinated as part of the national immunization program in a contemporaneous longitudinal cohort study. Longitudinal changes in serum antibody titers and association with pregnancy status were assessed using a two-step regression approach. Reactogenicity assessment in pregnant women was undertaken using an online questionnaire. The comparator group comprised non-pregnant women aged 18-49 years who had received two vaccine doses in primary care. The association of pregnancy status with reactogenicity was assessed using logistic regression analysis. RESULTS: Overall, 67 pregnant women, of whom 66 had received a mRNA vaccine, and 79 non-pregnant women, of whom 50 had received a mRNA vaccine, were included in the immunogenicity study. Most (61.2%) pregnant women received their first vaccine dose in the third trimester, while 3.0% received it in the first trimester and 35.8% in the second trimester. SARS-CoV-2 S-antibody geometric mean concentrations after mRNA vaccination were not significantly different at 2-6 weeks after the first dose but were significantly lower at 2-6 weeks after the second dose in infection-naïve pregnant compared with non-pregnant women. In pregnant women, prior infection was associated with higher antibody levels at 2-6 weeks after the second vaccine dose. Reactogenicity analysis included 108 pregnant women and 116 non-pregnant women. After the first dose, tiredness and chills were reported less commonly in pregnant compared with non-pregnant women (P = 0.043 and P = 0.029, respectively). After the second dose, feeling generally unwell was reported less commonly (P = 0.046) in pregnant compared with non-pregnant women. CONCLUSIONS: Using an extended 12-week interval between vaccine doses, antibody responses after two doses of mRNA COVID-19 vaccine were found to be lower in pregnant compared with non-pregnant women. Strong antibody responses were achieved after one dose in previously infected women, regardless of pregnancy status. Pregnant women reported fewer adverse events after both the first and second dose of vaccine. These findings should now be addressed in larger controlled studies. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Quantifying global soil carbon losses in response to warming.

The majority of the Earth's terrestrial carbon is stored in the soil. If anthropogenic warming stimulates the loss of this carbon to the atmosphere, it could drive further planetary warming. Despite evidence that warming enhances carbon fluxes to and from the soil, the net global balance between these responses remains uncertain. Here we present a comprehensive analysis of warming-induced changes in soil carbon stocks by assembling data from 49 field experiments located across North America, Europe and Asia. We find that the effects of warming are contingent on the size of the initial soil carbon stock, with considerable losses occurring in high-latitude areas. By extrapolating this empirical relationship to the global scale, we provide estimates of soil carbon sensitivity to warming that may help to constrain Earth system model projections. Our empirical relationship suggests that global soil carbon stocks in the upper soil horizons will fall by 30 ± 30 petagrams of carbon to 203 ± 161 petagrams of carbon under one degree of warming, depending on the rate at which the effects of warming are realized. Under the conservative assumption that the response of soil carbon to warming occurs within a year, a business-as-usual climate scenario would drive the loss of 55 ± 50 petagrams of carbon from the upper soil horizons by 2050. This value is around 12-17 per cent of the expected anthropogenic emissions over this period. Despite the considerable uncertainty in our estimates, the direction of the global soil carbon response is consistent across all scenarios. This provides strong empirical support for the idea that rising temperatures will stimulate the net loss of soil carbon to the atmosphere, driving a positive land carbon-climate feedback that could accelerate climate change.

Clinical value of weight-bearing CT and radiographs for detecting patellofemoral cartilage visualized by MRI in the MOST study.

OBJECTIVE: The patellofemoral joint is frequently affected by osteoarthritis (PFOA) and is incompletely imaged on radiographs (XR). Weight-Bearing CT (WBCT) could offer advantages for visualization. This study determined the sensitivity, specificity, and accuracy of axial WBCT and lateral XR for detection of PFOA features in comparison with cartilage damage on MRI. DESIGN: A convenience sample of 60 right knees from the MOST cohort were analyzed. WBCT and XR were read for OARSI JSN score and MRI for MOAKS cartilage score by two experienced musculoskeletal radiologists blinded to participant. Using MOAKS scoring on MRI (referent standard), the sensitivity, specificity and accuracy of patellofemoral OARSI JSN scores based on WBCT and XR were compared. RESULTS: The mean ± SD age and BMI for the participants included (66.7% women) were 67.6 ± 9.8 years and 30.0 ± 5.3 kg/m2 respectively. WBCT demonstrated significantly greater sensitivity (0.85-0.97 on WBCT vs 0.47-0.57 on XR) and accuracy (0.85-0.92 on WBCT vs 0.48-0.57 on XR) for all parameters except lateral full-thickness cartilage loss (McNemar's test p-values all <0.001). There was moderate-to-strong and low-to-moderate agreement between PFOA findings on WBCT and XR, respectively, and semi-quantitative scores of PF cartilage on MRI. Inter-rater reliability for XR JSN [weighted kappa = 0.83 (0.64, 1.0)], WBCT JSN [kappa = 0.60 (0.48, 0.72)] and MRI MOAKS-CM [kappa = 0.70 (0.61, 0.79)] readings were good. CONCLUSION: WBCT demonstrates significantly greater sensitivity and accuracy than radiographs for identification of PFOA. Given the same Relative Radiation Level as XR and improved visualization, WBCT holds promise to improve understanding of the weight-bearing patellofemoral joint.

Over half of seniors who start oral bisphosphonate therapy are exposed for 3 or more years: novel rolling window approach and patterns of use.

Most adherence studies only consider treatment following a first prescription. Using an extended follow-up, we found that 60% of seniors starting oral bisphosphonate therapy were exposed for ≥ 3 years (48% for ≥ 5 years). Studies are needed to examine the benefits and harms of continuing bisphosphonate therapy beyond 3 years. INTRODUCTION: The purpose of this study was to identify and describe patterns of long-term oral bisphosphonate use among seniors using a novel methodological approach that considers extended follow-up. METHODS: Among Ontarians aged 66 years or older, we identified subjects with a first dispensing of alendronate or risedronate between November 2000 and December 2016. We followed them until death or December 2019 to identify patients with ≥ 3 years of bisphosphonate use, defined as a proportion of days covered ≥ 80%, using 3-year rolling windows. We calculated the proportion of patients with long-term therapy (≥ 3 years of use) using Kaplan-Meier estimates. We described patterns of long-term use and compared patient characteristics between patients with and without long-term therapy. RESULTS: We identified 260,784 eligible seniors initiating bisphosphonate therapy. Of these, 60% continued therapy ≥ 3 years (77% women), and 48% continued ≥ 5 years. Characteristics did not meaningfully differ between patients with or without long-term therapy. The median length of long-term therapy was 7.0 (IQR 5.1) years for women and 6.1 (IQR 4.3) years for men. Only 20% experienced a treatment gap before long-term therapy, yet 50% experienced a treatment gap of ≥ 120 days after a median 5.3 years of therapy. Eighty-one percent who returned to therapy following a treatment gap re-initiated an oral bisphosphonate, with 18% switching to denosumab. CONCLUSIONS: Among seniors initiating oral bisphosphonates, we found that 60% receive at least 3 years of therapy when using an extended follow-up. Studies are needed to examine the benefits and harms of continuing bisphosphonate therapy beyond 3 years.

Observation of the Exotic Isotope

A ^{13}F resonance was observed following a charge-exchange reaction between a fast ^{13}O beam and a ^{9}Be target. The resonance was found in the invariant-mass distribution of 3p+^{10}C events and probably corresponds to a 5/2^{+} excited state. The ground state was also expected to be populated, but was not resolved from the background. The observed level decays via initial proton emissions to both the ground and first 2^{+} state of ^{12}O, which subsequently undergo 2p decay. In addition, there may also be a significant proton decay branch to the second 2^{+} level in ^{12}O. The wave function associated with the observed level may be collectivized due to coupling to the continuum as is it located just above the threshold for proton decay to the 2_{2}^{+} state of ^{12}O.

First Observation of the Four-Proton Unbound Nucleus

^{18}Mg was observed, for the first time, by the invariant-mass reconstruction of ^{14}O+4p events. The ground-state decay energy and width are E_{T}=4.865(34) MeV and Γ=115(100) keV, respectively. The observed momentum correlations between the five particles are consistent with two sequential steps of prompt 2p decay passing through the ground state of ^{16}Ne. The invariant-mass spectrum also provides evidence for an excited state at an excitation energy of 1.84(14) MeV, which is likely the first excited 2^{+} state. As this energy exceeds that for the 2^{+} state in ^{20}Mg, this observation provides an argument for the demise of the N=8 shell closure in nuclei far from stability. However, in open systems this classical argument for shell strength is compromised by Thomas-Ehrman shifts.

Microscale modelling of dielectrophoresis assembly processes.

This work presents a microscale approach for simulating the dielectrophoresis assembly of polarizable particles under an external electric field. The model is shown to capture interesting dynamical and topological features, such as the formation of chains of particles and their incipient aggregation into hierarchical structures. A quantitative characterization in terms of the number and size of these structures is also discussed. This computational model could represent a viable numerical tool to study the mechanical properties of particle-based hierarchical materials and suggest new strategies for enhancing their design and manufacture. This article is part of the theme issue 'Progress in mesoscale methods for fluid dynamics simulation'.

Ammonium fluoride's analogy to ice: Possibilities and limitations.

Ammonium fluoride, NH4F, is often seen as an analog to ice, with several of its solid phases closely resembling known ice phases. While its ionic and hydrogen-ordered nature puts topological constraints on the ice-like network structures it can form, it is not clear what consequences these constraints have for NH4F compound formation and evolution. Here, we explore computationally the reach and eventual limits of the ice analogy for ammonium fluoride. By combining data mining of known and hypothetical ice networks with crystal structure prediction and density functional calculations, we explore the high-pressure phase diagram of NH4F and host-guest compounds of its hydrides. Pure NH4F departs from ice-like behavior above 80 GPa with the emergence of close-packed ionic structures. The predicted stability of NH4F hydrides shows that NH4F can act as a host to small guest species, albeit in a topologically severely constraint configuration space. Finally, we explore the binary NH3-HF chemical space, where we find candidate structures for several unsolved polyfluoride phases; among them is the chemical analog to H2O2 dihydrate.

Temporomandibular joint dysfunction following the use of a supraglottic airway device during general anaesthesia: a prospective observational study.

Supraglottic airway devices are commonly used to manage the airway during general anaesthesia. There are sporadic case reports of temporomandibular joint dysfunction and dislocation following supraglottic airway device use. We conducted a prospective observational study of adult patients undergoing elective surgery where a supraglottic airway device was used as the primary airway device. Pre-operatively, all participants were asked to complete a questionnaire involving 12 points adapted from the Temporomandibular Joint Scale and the Liverpool Oral Rehabilitation Questionnaire. Objective measurements included inter-incisor distance as well as forward and lateral jaw movements. The primary outcome was the inter-incisor distance, an accepted measure of temporomandibular joint mobility. Both the questionnaire and measurements were repeated in the postoperative period and we analysed data from 130 participants. Mean (SD) inter-incisor distance in the pre- and postoperative period was 46.5 (7.2) mm and 46.3 (7.5) mm, respectively (p = 0.521) with a difference (95%CI) of 0.2 (-0.5 to 0.9) mm. Mean (SD) forward jaw movement in the pre- and postoperative period was 3.6 (2.4) mm and 3.9 (2.4) mm, respectively (p = 0.018). Mean (SD) lateral jaw movement to the right in the pre- and postoperative period was 8.9 (4.1) mm and 9.1 (4.0) mm, respectively (p = 0.314). Mean (SD) lateral jaw movement to the left in the pre- and postoperative period was 8.8 (4.0) mm and 9.3 (3.6) mm, respectively (p = 0.008). The number of patients who reported jaw clicks or pops before opening their mouth as wide as possible was 28 (21.5%) vs. 12 (9.2%) in the pre- and postoperative period, respectively (p < 0.001) with a difference (95%CI) of 12.3% (6.7-17.9%). There was no significant difference in the responses to the other 11 questions or in the number of patients who reported pain in the temporomandibular joint area postoperatively. No clinically significant dysfunction of the temporomandibular joint following the use of supraglottic airway devices in the postoperative period was identified by either patient questionnaires or objective measurements.

Quantitative sensory testing in feline osteoarthritic pain - a systematic review and meta-analysis.

Quantitative sensory testing (QST) is a psychophysical test used to quantify somatosensory sensation under normal or pathological conditions including osteoarthritis (OA). OBJECTIVE: This study aimed to conduct a systematic review and meta-analysis of studies using QST in healthy and osteoarthritic cats, registered at Systematic Review Research Facility (#26-06-2017). DESIGN: Hierarchical models with random intercepts for each individual study extracted through the systematic review were fit to subject-level data; QST measures were contrasted between healthy and osteoarthritic cats. Four bibliographic databases were searched; quality and risk of bias assessment were performed using pre-established criteria. RESULTS: Six articles were included; most were of high quality and low risk of bias. Punctate tactile threshold (n = 70) and mechanical temporal summation (n = 35) were eligible for analysis. Cats with OA have lower punctate tactile threshold [mean difference (95%HDI): -44 (-60; -26) grams] and facilitated temporal summation of pain [hazard ratio (95%HDI): 5.32 (2.19; 14) times] when compared with healthy cats. The effect of sex and body weight on sensory sensitivity remained inconclusive throughout all analyses. Due to the correlation between age and OA status, it remains difficult to assess the effect of OA on sensory sensitivity, independently of age. CONCLUSIONS: Clear and transparent reporting using guidelines are warranted. Similar to people, centralized sensitization is a feature of OA in cats. Future studies should try to elucidate the age effect on feline OA. Research with natural OA in cats is promising with potential to benefit feline health and welfare, and improve translatability to clinical research.

Shape Changes in the N=28 Island of Inversion: Collective Structures Built on Configuration-Coexisting States in

The neutron-rich nuclei in the N=28 island of inversion have attracted considerable experimental and theoretical attention, providing great insight into the evolution of shell structure and nuclear shape in exotic nuclei. In this work, for the first time, quadrupole collectivity is assessed simultaneously on top of the 3/2^{-} ground state and the 7/2^{-} shape-coexisting isomer of ^{43}S, putting the unique interpretation of shape and configuration coexistence at N=27 and 28 in the sulfur isotopic chain to the test. From an analysis of the electromagnetic transition strengths and quadrupole moments predicted within the shell model, it is shown that the onset of shape coexistence and the emergence of a simple collective structure appear suddenly in ^{43}S with no indication of such patterns in the N=27 isotone ^{45}Ar.

Antiretroviral Adherence, Drug Resistance, and the Impact of Social Determinants of Health in HIV-1 Patients in the US.

Adherence to antiretroviral therapy (ART) is critical to achieving viral suppression. However, social determinants of health (SDoH) can undermine patient adherence to ART, resulting in drug resistance that compromises future treatment options. We assessed ART adherence and HIV-1 drug resistance at the national and state levels in the US and investigated their associations with SDoH and other HIV-related outcomes. Data were obtained from Symphony Health's Integrated Dataverse (IDV), Monogram/LabCorp Database, as well as national and publicly available databases, including Centers for Disease Control and Prevention (CDC), American Community Survey (ACS), and J. Kaiser Family Foundation (KFF). Inferential analyses were performed to investigate associations using patient-level data, and the results were reported by state and overall within the nation. Correlations between continuous variables were estimated by the Spearman's test, and that between continuous variable and categorical variable were estimated using one-way analysis of variance (ANOVA). State-level rates of poor adherence and resistance ranged from 26 to 55% and 20 to 54%, respectively. Female gender, non-white race, low education, poverty, and unemployment were associated with poor adherence; female gender was associated with drug resistance. Both adherence and resistance were correlated to HIV prevalence rates. Our findings suggest that US patients living with HIV face great challenges associated with poor ART adherence and HIV-1 drug resistance.

Insight into the Chemistry of PETN Under Shock Compression Through Ultrafast Broadband Mid-Infrared Absorption Spectroscopy.

Thin films of pentaerythritol tetranitrate (PETN) were shock compressed using the laser driven shock apparatus at Los Alamos National Laboratory (LANL). Two spectroscopic probes were available to this apparatus: visible white light transient absorption spectroscopy (VIS) from 400 to 700 nm and mid-infrared transient absorption spectroscopy (MIR) from 1150 to 3800 cm-1. Important PETN vibrational modes are the symmetric and antisymmetric NO2 stretches at 1280 and 1650 cm-1, respectively, as well as CH stretches at ∼2900 cm-1. Shock strength was varied from approximately 3 to 55 GPa to span from the chemically unreactive regime to the regime in which fast chemical reaction took place on the 250 ps time scale of the measurements. VIS and MIR results suggest irreversible chemistry was induced in PETN at pressures above 30 GPa. At lower shock pressures, the spectroscopy showed minimal changes attributable to pressure induced effects. Under the higher-pressure reactive conditions, the frequency region at the antisymmetric NO2 stretch mode had a significantly increased absorption while the region around the symmetric NO2 stretch did not. No observable increased absorption occurred in the higher frequency regions where CH-, NH-, and OH- bond absorptions would be observed. A broad absorption appeared on the shoulder at the red-edge of the CO2 vibrational band around 2200 cm-1. In addition to the experiments, reactive molecular dynamics were carried out under equivalent shock conditions to correlate the evolution of the infrared spectrum to molecular processes. The simulations show results consistent to experiments up to 30 GPa but suggest that NO and NO2 related features provided the strongest contributions to the shocked infrared changes. Proposed mechanisms for shocked PETN chemistry are analyzed as consistent or inconsistent with the data presented here. Our experimental data suggests C≡O or N2O bond formation, nitrite formation, and absence of significant hydroxyl or amine concentrations in the initial chemistry steps in PETN shocked above 30 GPa.

Is neoadjuvant chemoradiotherapy sufficient in patients with advanced rectal malignancy and positive extra-mesorectal lateral lymph nodes?

AIM: There is current debate about the optimal management of lateral pelvic lymph nodes (LPLNs) in rectal cancer between Western and Eastern centres. This paper aims to report the rate of histologically proven positive LPLNs in a group of patients undergoing the conventional Western approach to primary and recurrent rectal cancer. METHOD: A retrospective cohort review of all patients who underwent LPLN dissection at Royal Prince Alfred Hospital in Sydney, Australia. This included patients who underwent pelvic exenteration who had LPLNs excised either en bloc for laterally invasive or recurrent tumours or as part of selective node dissection for suspicious lymph nodes on preoperative imaging. Histopathological results for these patients were compared with node status at preoperative imaging. RESULTS: Seventy-one patients satisfied the inclusion criteria. Of those patients with positive nodes on histology, 27% (9/33) with radiologically positive LPLNs were treated with preoperative radiotherapy and 75% (9/12) with radiologically positive LPLNs were not treated with preoperative radiotherapy (P = 0.004). None of the 12 patients with radiologically negative nodes treated with radiotherapy had positive nodes; 25% (3/12) of the patients with radiologically negative nodes who were not treated with radiotherapy had positive nodes. Fifty-three per cent of patients developed postoperative complications. CONCLUSION: Our study suggests that in patients with radiologically positive LPLNs chemoradiotherapy may not be enough to sterilize these extra-mesorectal lymph nodes as a large proportion (27%) will have residual viable adenocarcinoma cells. In patients with radiologically negative LPLNs, however, the addition of chemoradiotherapy may serve to adequately sterilize these lymph nodes without the need for prophylactic LPLN dissection.

Tunable spin-spin interactions and entanglement of ions in separate potential wells.

Quantum simulation--the use of one quantum system to simulate a less controllable one--may provide an understanding of the many quantum systems which cannot be modelled using classical computers. Considerable progress in control and manipulation has been achieved for various quantum systems, but one of the remaining challenges is the implementation of scalable devices. In this regard, individual ions trapped in separate tunable potential wells are promising. Here we implement the basic features of this approach and demonstrate deterministic tuning of the Coulomb interaction between two ions, independently controlling their local wells. The scheme is suitable for emulating a range of spin-spin interactions, but to characterize the performance of our set-up we select one that entangles the internal states of the two ions with a fidelity of 0.82(1) (the digit in parentheses shows the standard error of the mean). Extension of this building block to a two-dimensional network, which is possible using ion-trap microfabrication processes, may provide a new quantum simulator architecture with broad flexibility in designing and scaling the arrangement of ions and their mutual interactions. To perform useful quantum simulations, including those of condensed-matter phenomena such as the fractional quantum Hall effect, an array of tens of ions might be sufficient.

Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes.

BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.

The role of MRI pelvimetry in predicting technical difficulty and outcomes of open and minimally invasive total mesorectal excision: a systematic review.

BACKGROUND: The difficulty of performing total mesorectal excision (TME) for rectal cancer partly relies on the surgeon's subjective assessment of the individual patient's pelvic anatomy and tumour characteristics, which generally influences the choice of platform used (open, laparoscopic, robotic or trans-anal surgery). Recent studies have found associations between several anatomical pelvic measurements and surgical difficulty. The aim of this study was to systematically review existing data reporting the use of magnetic resonance imaging (MRI)-based pelvic measurements to predict technical difficulty and outcomes of TME, and determine whether pelvimetry could optimise patient-specific selection of a particular surgical approach. METHODS: MEDLINE, Embase and Cochrane Library databases were systematically searched for studies reporting MRI-based pelvic measurements in patients undergoing surgery for rectal cancer, and the effect of these measurements on surgical difficulty. RESULTS: Eleven studies reporting the association between MRI-pelvimetry measurements and rectal cancer surgical outcomes were included. Indicators for surgical difficulty used in the included studies were involved circumferential resection margin, longer operative time, incomplete TME, higher blood loss, anastomotic leak, conversion to open surgery and overall complications. Bony pelvic measurements which were associated with increased surgical difficulty in more than one study were a smaller interspinous distance, a smaller intertubercle distance, a smaller pelvic inlet and larger pubic tubercle height. Two studies identified larger mesorectal fat area as a predictor of surgical difficulty. CONCLUSIONS: Bony pelvic measurements may predict surgical difficulty during TME, however, use of different indicators of difficulty limit comparison between studies. Early data suggest MRI soft tissue measurements may predict surgical difficulty and warrants further investigation.

Zebrafish sp7 mutants show tooth cycling independent of attachment, eruption and poor differentiation of teeth.

The capacity to fully replace teeth continuously makes zebrafish an attractive model to explore regeneration and tooth development. The requirement of attachment bone for the appearance of replacement teeth has been hypothesized but not yet investigated. The transcription factor sp7 (osterix) is known in mammals to play an important role during odontoblast differentiation and root formation. Here we study tooth replacement in the absence of attachment bone using sp7 zebrafish mutants. We analysed the pattern of tooth replacement at different stages of development and demonstrated that in zebrafish lacking sp7, attachment bone is never present, independent of the stage of tooth development or fish age, yet replacement is not interrupted. Without bone of attachment we observed abnormal orientation of teeth, and abnormal connection of pulp cavities of predecessor and replacement teeth. Mutants lacking sp7 show arrested dentinogenesis, with non-polarization of odontoblasts and only a thin layer of dentin deposited. Osteoclast activity was observed in sp7 mutants; due to the lack of bone of attachment, remodelling was diminished but nevertheless present along the pharyngeal bone. We conclude that tooth replacement is ongoing in the sp7 mutant despite poor differentiation and defective attachment. Without bone of attachment tooth orientation and pulp organization are compromised.