Author Correction: Future response of global coastal wetlands to sea-level rise.

Change history: In Fig. 2b of this Letter, 'Relative wetland change (km2)' should have read 'Relative wetland change (%)' and equations (2) and (3) have been changed from 'RSLRcrit = (m × TRe) × Sed + i' and 'Sedcrit = (RSLR - i)/(m × TRe)', respectively. The definition of the variables in equation (2) has been updated. These errors have been corrected online.

EnderScope: a low-cost 3D printer-based scanning microscope for microplastic detection.

Low-cost and scalable technologies that allow people to measure microplastics in their local environment could facilitate a greater understanding of the global problem of marine microplastic pollution. A typical way to measure marine microplastic pollution involves imaging filtered seawater samples stained with a fluorescent dye to aid in the detection of microplastics. Although traditional fluorescence microscopy allows these particles to be manually counted and detected, this is a resource- and labour-intensive task. Here, we describe a novel, low-cost microscope for automated scanning and detection of microplastics in filtered seawater samples-the EnderScope. This microscope is based on the mechanics of a low-cost 3D printer (Creality Ender 3). The hotend of the printer is replaced with an optics module, allowing for the reliable and calibrated motion system of the 3D printer to be used for automated scanning over a large area (>20 × 20 cm). The EnderScope is capable of both reflected light and fluorescence imaging. In both configurations, we aimed to make the design as simple and cost-effective as possible, for example, by using low-cost LEDs for illumination and lighting gels as emission filters. We believe this tool is a cost-effective solution for microplastic measurement. This article is part of the Theo Murphy meeting issue 'Open, reproducible hardware for microscopy'.

Future response of global coastal wetlands to sea-level rise.

The response of coastal wetlands to sea-level rise during the twenty-first century remains uncertain. Global-scale projections suggest that between 20 and 90 per cent (for low and high sea-level rise scenarios, respectively) of the present-day coastal wetland area will be lost, which will in turn result in the loss of biodiversity and highly valued ecosystem services1-3. These projections do not necessarily take into account all essential geomorphological4-7 and socio-economic system feedbacks8. Here we present an integrated global modelling approach that considers both the ability of coastal wetlands to build up vertically by sediment accretion, and the accommodation space, namely, the vertical and lateral space available for fine sediments to accumulate and be colonized by wetland vegetation. We use this approach to assess global-scale changes in coastal wetland area in response to global sea-level rise and anthropogenic coastal occupation during the twenty-first century. On the basis of our simulations, we find that, globally, rather than losses, wetland gains of up to 60 per cent of the current area are possible, if more than 37 per cent (our upper estimate for current accommodation space) of coastal wetlands have sufficient accommodation space, and sediment supply remains at present levels. In contrast to previous studies1-3, we project that until 2100, the loss of global coastal wetland area will range between 0 and 30 per cent, assuming no further accommodation space in addition to current levels. Our simulations suggest that the resilience of global wetlands is primarily driven by the availability of accommodation space, which is strongly influenced by the building of anthropogenic infrastructure in the coastal zone and such infrastructure is expected to change over the twenty-first century. Rather than being an inevitable consequence of global sea-level rise, our findings indicate that large-scale loss of coastal wetlands might be avoidable, if sufficient additional accommodation space can be created through careful nature-based adaptation solutions to coastal management.

Comparing oncological outcomes of robotic versus open surgery in the treatment of endometrial cancer.

PURPOSE: Robotic surgery has been incorporated in the treatment of endometrial cancer, with evidence suggesting that minimal access surgery offers advantages over laparotomy including less blood loss, lower rate of perioperative complications, and accelerated postoperative recovery. The laparoscopic approach to cervical cancer (LACC) study has recently demonstrated inferior survival outcomes in cervical cancer patients treated with minimal access surgery including robotic surgery. It is, therefore, imperative that further evaluation of the latter in endometrial cancer is performed. METHODS: A retrospective analysis of clinical data was performed. We compared two different types of surgery performed for the treatment of FIGO stage 1 to 3 endometrial cancer; open surgery performed in the years 2013-2015 vs robotic surgery performed in 2017-2019, after the implementation of the robotic program in our institution. Main outcome measures were recurrence-free survival and overall survival, with secondary outcomes including surgical morbidity and postoperative recovery. RESULTS: We compared 123 patients who had open surgery with 104 patients who underwent robotic surgery. One case from the second group was converted to open surgery due to the inability to complete it robotically. After a median follow-up of 68 months, there was no difference in recurrence-free survival or overall survival between the two groups. Length of stay after an operation was significantly different with mean hospital stay of 1.6 days after robotic surgery and 5 days after open surgery (p = 0.001). No significant difference was identified in the rate of complications (p = 0.304). CONCLUSION: Our analysis has demonstrated that robotic surgery offers better perioperative outcomes without compromising the oncological safety.

Shape modelling of the oropharynx distinguishes associations with body morphology but not whiplash-associated disorder.

Characterization of the oropharynx, a subdivision of the pharynx between the soft palate and the epiglottis, is limited to simple measurements. Structural changes in the oropharynx in whiplash-associated disorder (WAD) cohorts have been quantified using two-dimensional (2D) and three-dimensional (3D) measures but the results are inconsistent. Statistical shape modelling (SSM) may be a more useful tool for systematically comparing morphometric features between cohorts. This technique has been used to quantify the variability in boney and soft tissue structures, but has not been used to examine a hollow cavity such as the oropharynx. The primary aim of this project was to examine the utility of SSM for comparing the oropharynx between WAD cohorts and control; and WAD severity cohorts. The secondary aim was to determine whether shape is associated with sex, height, weight and neck length. Magnetic resonance (MR) T1-weighted images were obtained from healthy control (n = 20), acute WAD (n = 14) and chronic WAD (n = 14) participants aged 18-39 years. Demographic, WAD severity (neck disability index) and body morphometry data were collected from each participant. Manual segmentation of the oropharynx was undertaken by blinded researchers between the top of the soft palate and tip of the epiglottis. Digital 3D oropharynx models were constructed from the segmented images and principal component (PC) analysis was performed with the PC weights normalized to z-scores for consistency. Statistical analyses were undertaken using multivariate linear models. In the first statistical model the independent variable was group (acute WAD, chronic WAD, control); and in the second model the independent variable was WAD severity (recovered/mild, moderate/severe). The covariates for both models included height, weight, average neck length and sex. Shape models were constructed to visualize the effect of perturbing these covariates for each relevant mode. The shape model revealed five modes which explained 90% of the variance: mode 1 explained 59% of the variance and primarily described differences in isometric size of the oropharynx, including elongation; mode 2 (13%) primarily described lateral (width) and AP (depth) dimensions; mode 3 (8%) described retroglossal AP dimension; mode 4 (6%) described lateral dimensions at the retropalatal-retroglossal junction and mode 5 (4%) described the lateral dimension at the inferior retroglossal region. There was no difference in shape (mode 1 p = 0.52; mode 2 p = 0.96; mode 3 p = 0.07; mode 4 p = 0.54; mode 5 p = 0.74) between control, acute WAD and chronic WAD groups. There were no statistical differences for any mode (mode 1 p = 0.12; mode 2 p = 0.29; mode 3 p = 0.56; mode 4 p = 0.99; mode 5 p = 0.96) between recovered/mild and moderate/severe WAD. Sex was not significant in any of the models but for mode 1 there was a significant association with height (p = 0.007), mode 2 neck length (p = 0.044) and in mode 3 weight (p = 0.027). Although SSM did not detect differences between WAD cohorts, it did detect associations with body morphology indicating that it may be a useful tool for examining differences in the oropharynx.

Statistical shape modelling reveals differences in hamstring morphology between professional rugby players and sprinters.

Hamstring morphology may play an important role in understanding the aetiology of hamstring injury. Currently, the methods available to capture detailed morphological data such as muscle shape have not been utilized for the hamstring muscles. The aim of this study was to examine the utility of statistical shape modelling (SSM) for describing and comparing hamstring muscle shape in rugby and sprinting athletes. Magnetic resonance images of both thighs of nine elite male rugby players and nine track and field sprinters were analysed. Images were converted to three-dimensional models enabling generation of four statistical shape models. Principal components describing the shape variation in the cohort were derived and evaluated. Six principal components were sufficient to discriminate differences in the shape of the hamstring muscles of rugby and sprinting athletes with 89% classification accuracy. Distinct shape features distinguishing rugby players from sprinters included size, curvature and axial torsion. These data demonstrate that SSM is useful for understanding hamstring muscle shape and that meaningful variation can be identified within a small sample. This method can be used in future research to enhance the anatomical specificity of musculoskeletal modelling and to understand the relationship between hamstring shape and injury.

Hamstring musculotendon mechanics of prospectively injured elite rugby athletes.

The musculotendon mechanics of the hamstrings during high-speed running are thought to relate to injury but have rarely been examined in the context of prospectively occurring injury. This prospective study describes the hamstring musculotendon mechanics of two elite rugby players who sustained hamstring injuries during on-field running. Athletes undertook biomechanical analyses of high-speed running during a Super Rugby pre-season, prior to sustaining hamstring injuries during the subsequent competition season. The biceps femoris long head muscle experienced the greatest strain of all hamstring muscles during the late swing phase. When expressed relative to force capacity, biceps femoris long head also experienced the greatest musculotendon forces of all hamstring muscles. Musculotendon strain and force may both be key mechanisms for hamstring injury during the late swing phase of running.

Bands of Fontana are caused exclusively by the sinusoidal path of axons in peripheral nerves and predict axon path; evidence from rodent nerves and physical models.

The precise cause of the bands of Fontana, striations on peripheral nerves visible to the naked eye, has been the subject of debate for hundreds of years. Some researchers have described them as reflecting the sinuous course of nerve fibres passing through nerves, and others have proposed that endoneurial collagen and sheaths surrounding nerves play a role in their appearance. We hypothesised that the bands are caused exclusively by reflection of light from the surfaces of nerve fibres travelling in phase in sinusoidal waveforms through peripheral nerves. We aligned images of obliquely illuminated nerves with confocal images of axons in those nerves, and the numbers and positions of the bands precisely matched the axonal waves. We also developed three-dimensional models of nerves with representations of the sinusoidal path of axons at their surface. We observed patterns resembling the bands of Fontana when these models were obliquely illuminated. This provides evidence that the bands of Fontana can be caused by light reflected sinusoidal path of axons alone. We subsequently describe a mechanism of band production based on our observations of both nerves and models. We report that smaller diameter nerves such as phrenic nerves and distal branches of sciatic nerves have shorter band intervals than larger nerves, such as proximal trunks of sciatic nerves, and that shorter band intervals correlate with longer axons per unit length of nerve, which suggests a greater tolerance to stretch. Inspection of banding patterns on peripheral nerves may permit prediction of axon length within nerves, and assist in the interpretation of nerve conduction data, especially in diseases where axon path has become altered.

Orthogonal Chirp-Based Ultrasonic Positioning.

This paper presents a chirp based ultrasonic positioning system (UPS) using orthogonal chirp waveforms. In the proposed method, multiple transmitters can simultaneously transmit chirp signals, as a result, it can efficiently utilize the entire available frequency spectrum. The fundamental idea behind the proposed multiple access scheme is to utilize the oversampling methodology of orthogonal frequency-division multiplexing (OFDM) modulation and orthogonality of the discrete frequency components of a chirp waveform. In addition, the proposed orthogonal chirp waveforms also have all the advantages of a classical chirp waveform. Firstly, the performance of the waveforms is investigated through correlation analysis and then, in an indoor environment, evaluated through simulations and experiments for ultrasonic (US) positioning. For an operational range of approximately 1000 mm, the positioning root-mean-square-errors (RMSEs) &90% error were 4.54 mm and 6.68 mm respectively.

Anatomic variations of levator scapulae in a normal cohort: an MRI study.

PURPOSE: Accessory attachments of the levator scapulae (LS) muscle have been described in the literature in previous cadaveric studies, but there is little knowledge about the incidence and distribution. Knowledge of LS accessory attachments is relevant to clinicians working in the fields of radiology, surgery, neurology, and musculoskeletal medicine. The purpose of this study was to explore the incidence and spectrum of LS caudal accessory attachments in vivo using magnetic resonance (MR) imaging in a young cohort. METHODS: MR images of the cervical spine were obtained from 37 subjects (13 males and 24 females) aged 18-36 years using an axial T1-weighted spin echo sequence acquired from a 3-Tesla MR scanner. The LS muscle was identified, and the presence of caudal accessory attachments was recorded and described. RESULTS: LS caudal accessory attachments were identified in 16 subjects (4 right, 6 left, and 6 bilateral; 12 female). Ten had unilateral accessory attachments to the serratus anterior, serratus posterior superior or the first/second rib. Four had bilateral accessory attachments to serratus anterior. One had bilateral accessory attachments to serratus posterior superior and unilateral accessory attachment to serratus anterior. One had bilateral attachments to both muscles. CONCLUSIONS: Both unilateral and bilateral LS caudal accessory attachments were present in nearly half of the subjects examined. They were relatively more frequent in females than males. The findings indicate that these accessory attachments are common, and in some cases, those accessory attachments can occur bilaterally and to more than one site.

The connecting health and technology study: a 6-month randomized controlled trial to improve nutrition behaviours using a mobile food record and text messaging support in young adults.

BACKGROUND: Early adulthood represents the transition to independent living which is a period when changes in diet and body weight are likely to occur. This presents an ideal time for health interventions to reduce the effect of health problems and risk factors for chronic disease in later life. As young adults are high users of mobile devices, interventions that use this technology may improve engagement. The Connecting Health and Technology study aimed to evaluate the effectiveness of tailored dietary feedback and weekly text messaging to improve dietary intake of fruit, vegetables and junk food over 6 months among a population-based sample of men and women (aged 18-30 years). METHODS: A three-arm, parallel, randomized control trial was conducted. After baseline assessments, participants were randomized to one of three groups: A) dietary feedback and weekly text messages, B) dietary feedback only or C) control group. Dietary intake was assessed using a mobile food record App (mFR) where participants captured images of foods and beverages consumed over 4-days at baseline and post-intervention. The primary outcomes were changes in serves of fruits, vegetables, energy-dense nutrient-poor (EDNP) foods and sugar-sweetened beverages (SSB). The intervention effects were assessed using linear mixed effect models for change in food group serves. RESULTS: Young adults (n = 247) were randomized to group A (n = 82), group B (n = 83), or group C (n = 82). Overall, no changes in food group serves for either intervention groups were observed. An unanticipated outcome was a mean weight reduction of 1.7 kg (P = .02) among the dietary feedback only. Men who received dietary feedback only, significantly reduced their serves of EDNP foods by a mean of 1.4 serves/day (P = .02). Women who received dietary feedback only significantly reduced their intake of SSB (P = .04) by an average of 0.2 serves/day compared with controls. CONCLUSIONS: Tailored dietary feedback only resulted in a decrease in EDNP foods in men and SSB in women, together with a reduction in body weight. Using a mobile food record for dietary assessment and tailored feedback has great potential for future health promotion interventions targeting diet and weight in young adults. TRIAL REGISTRATION: Australian Clinical Trials Registry Registration number: ACTRN12612000250831 .

Speckle-reduction algorithm for ultrasound images in complex wavelet domain using genetic algorithm-based mixture model.

Compared with other medical-imaging modalities, ultrasound (US) imaging is a valuable way to examine the body's internal organs, and two-dimensional (2D) imaging is currently the most common technique used in clinical diagnoses. Conventional 2D US imaging systems are highly flexible cost-effective imaging tools that permit operators to observe and record images of a large variety of thin anatomical sections in real time. Recently, 3D US imaging has also been gaining popularity due to its considerable advantages over 2D US imaging. It reduces dependency on the operator and provides better qualitative and quantitative information for an effective diagnosis. Furthermore, it provides a 3D view, which allows the observation of volume information. The major shortcoming of any type of US imaging is the presence of speckle noise. Hence, speckle reduction is vital in providing a better clinical diagnosis. The key objective of any speckle-reduction algorithm is to attain a speckle-free image while preserving the important anatomical features. In this paper we introduce a nonlinear multi-scale complex wavelet-diffusion based algorithm for speckle reduction and sharp-edge preservation of 2D and 3D US images. In the proposed method we use a Rayleigh and Maxwell-mixture model for 2D and 3D US images, respectively, where a genetic algorithm is used in combination with an expectation maximization method to estimate mixture parameters. Experimental results using both 2D and 3D synthetic, physical phantom, and clinical data demonstrate that our proposed algorithm significantly reduces speckle noise while preserving sharp edges without discernible distortions. The proposed approach performs better than the state-of-the-art approaches in both qualitative and quantitative measures.

Intelligent estimation of noise and blur variances using ANN for the restoration of ultrasound images.

Ultrasound (US) imaging is a widely used clinical diagnostic tool in medical imaging techniques. It is a comparatively safe, economical, painless, portable, and noninvasive real-time tool compared to the other imaging modalities. However, the image quality of US imaging is severely affected by the presence of speckle noise and blur during the acquisition process. In order to ensure a high-quality clinical diagnosis, US images must be restored by reducing their speckle noise and blur. In general, speckle noise is modeled as a multiplicative noise following a Rayleigh distribution and blur as a Gaussian function. Hereto, we propose an intelligent estimator based on artificial neural networks (ANNs) to estimate the variances of noise and blur, which, in turn, are used to obtain an image without discernible distortions. A set of statistical features computed from the image and its complex wavelet sub-bands are used as input to the ANN. In the proposed method, we solve the inverse Rayleigh function numerically for speckle reduction and use the Richardson-Lucy algorithm for de-blurring. The performance of this method is compared with that of the traditional methods by applying them to a synthetic, physical phantom and clinical data, which confirms better restoration results by the proposed method.

Magnetic resonance imaging atlas of the cervical spine musculature.

The anatomy of the cervical spine musculature visible on magnetic resonance (MR) images is poorly described in the literature. However, the correct identification of individual muscles is clinically important because certain conditions of the cervical spine, for example whiplash associated disorders, idiopathic neck pain, cervical nerve root avulsion and cervical spondylotic myelopathy, are associated with different morphological changes in specific muscles visible on MR images. Knowledge of the precise structure of different cervical spine muscles is crucial when comparisons with the contralateral side or with normal are required for accurate description of imaging pathology, management and assessment of treatment efficacy. However, learning the intricate arrangement of 27 muscles is challenging. A multi-level cross-sectional depiction combined with three-dimensional reconstructions could facilitate the understanding of this anatomically complex area. This paper presents a comprehensive series of labeled axial MR images from one individual and serves as a reference atlas of the cervical spine musculature to guide clinicians, researchers, and anatomists in the accurate identification of these muscles on MR imaging. Clin. Anat. 29:643-659, 2016. © 2016 Wiley Periodicals, Inc.

Normal nerve striations are altered in the trembler-J mouse, a model of Charcot-Marie-Tooth disease.

INTRODUCTION: This study was initiated because it was noted that the peripheral nerves of Trembler-J mice (a model of human Charcot-Marie-Tooth disease) appear to lack normal striations. METHODS: We performed confocal microscopy of whole sciatic nerves and tested the effect of axial stress on impulse conduction. RESULTS: We found that the axons of mutant mice were longer than those of the wild-type (1.55 mm of axon/mm length of nerve vs. 1.28 mm/mm respectively). This axonal elongation altered the helical nerve striations (bands of Fontana). As nerves were stretched axially, the conduction distance became correspondingly shorter. The effect on latency was significantly greater in the more coiled nerves of Trembler-J mice (P = 0.038). CONCLUSIONS: The finding that mice with a mutated peripheral myelin protein 22 (PMP22) possess excessively long axons may be related to the excess Schwann cell numbers found in this disorder.

Medial and lateral hamstrings and quadriceps co-activation affects knee joint kinematics and ACL elongation: a pilot study.

BACKGROUND: Many injury prevention and rehabilitation programs aim to train hamstring and quadriceps co-activation to constrain excessive anterior tibial translation and protect the anterior cruciate ligament (ACL) from injury. However, despite strong clinical belief in its efficacy, primary evidence supporting training co-activation of the hamstrings and quadriceps muscles for ACL injury prevention and rehabilitation is quite limited. Therefore, the purpose of the study presented in this paper was to determine if hamstring-quadriceps co-activation alters knee joint kinematics, and also establish if it affects ACL elongation. METHODS: A computed tomography (CT) scan from each participant's dominant leg was acquired prior to performing two step-ups under fluoroscopy: one with 'natural' hamstring-quadriceps co-activation, one with deliberate co-activation. Electromyography was used to confirm increased motor unit recruitment. The CT scan was registered to fluoroscopy for 4-D modeling, and knee joint kinematics subsequently measured. Anterior cruciate ligament attachments were mapped to the 4-D models and its length was assumed from the distance between attachments. Anterior cruciate ligament elongation was derived from the change in distance between those points as they moved relative to each other. RESULTS: Reduced ACL elongation as well as knee joint rotation, abduction, translation, and distraction was observed for the step up with increased co-activation. A relationship was shown to exist for change in ACL length with knee abduction (r = 0.91; p ≤ 0.001), with distraction (r = -0.70; p = 0.02 for relationship with compression), and with anterior tibial translation (r = 0.52; p = 0.01). However, ACL elongation was not associated with internal rotation or medial translation. Medial hamstring-quadriceps co-activation was associated with a shorter ACL (r = -0.71; p = 0.01), and lateral hamstring-quadriceps co-activation was related to ACL elongation (r = 0.46; p = 0.05). CONCLUSION: Net co-activation of the hamstrings and quadriceps muscles will likely reduce ACL elongation provided that the proportion of medial hamstring-quadriceps co-activation exceeds lateral.

Accuracy assessment of Tri-plane B-mode ultrasound for non-invasive 3D kinematic analysis of knee joints.

BACKGROUND: Currently the clinical standard for measuring the motion of the bones in knee joints with sufficient precision involves implanting tantalum beads into the bones. These beads appear as high intensity features in radiographs and can be used for precise kinematic measurements. This procedure imposes a strong coupling between accuracy and invasiveness. In this paper, a tri-plane B-mode ultrasound (US) based non-invasive approach is proposed for use in kinematic analysis of knee joints in 3D space. METHODS: The 3D analysis is performed using image processing procedures on the 2D US slices. The novelty of the proposed procedure and its applicability to the unconstrained 3D kinematic analysis of knee joints is outlined. An error analysis for establishing the method's feasibility is included for different artificial compositions of a knee joint phantom. Some in-vivo and in-vitro scans are presented to demonstrate that US scans reveal enough anatomical details, which further supports the experimental setup used using knee bone phantoms. RESULTS: The error between the displacements measured by the registration of the US image slices and the true displacements of the respective slices measured using the precision mechanical stages on the experimental apparatus is evaluated for translation and rotation in two simulated environments. The mean and standard deviation of errors are shown in tabular form. This method provides an average measurement precision of less than 0.1 mm and 0.1 degrees, respectively. CONCLUSION: In this paper, we have presented a novel non-invasive approach to measuring the motion of the bones in a knee using tri-plane B-mode ultrasound and image registration. In our study, the image registration method determines the position of bony landmarks relative to a B-mode ultrasound sensor array with sub-pixel accuracy. The advantages of our proposed system over previous techniques are that it is non-invasive, does not require the use of ionizing radiation and can be used conveniently if miniaturized.

Shape modelling reveals age-related knee bony shape changes in asymptomatic knees.

Osteoarthritis (OA) causes bony shape changes within the knee. Furthermore, the risk of developing OA increases with age. However, age alone does not cause OA. It is therefore important to understand the healthy age-related trajectories of knee shape before attributing these changes to OA. The aim of this study was to determine the association between bony knee shape and age using statistical-shape modelling (SSM). 96 participants received a CT scan of their knee. Three-dimensional models were created using manual segmentation. Separate SSM's for the distal femur and proximal tibia were created. Linear regression models were used to assess the association between age and femoral and tibial shape. Fourteen modes of the femoral and tibial SSM's captured 68% and 73% shape variation, respectively. Only femoral mode 3 and tibial mode 7 were associated with age. Increasing age was related to larger femoral bone volume and deepening of the femoral trochlear groove. Furthermore, increased age was associated with medial tibial plateau expansion. Aspects of bony femoral and tibial shape were significantly associated with aging, including femoral and tibial bone size, femoral trochlear groove, and medial tibial plateau area. Changes in knee morphology occur as a normal process of aging without osteoarthritis development. This may be a response to mechanical loading over time. Further research investigating the effect of these changes on loading in the knee may provide valuable information for knee health in older age.

Management of unscheduled bleeding on HRT: A joint guideline on behalf of the British Menopause Society, Royal College Obstetricians and Gynaecologists, British Gynaecological Cancer Society, British Society for Gynaecological Endoscopy, Faculty of Sexual and Reproductive Health, Royal College of General Practitioners and Getting it Right First Time.

Unscheduled bleeding on hormone replacement therapy (HRT) can affect up to 40% of users. In parallel with the increase in HRT prescribing in the UK, there has been an associated increase in referrals to the urgent suspicion of cancer pathway for unscheduled bleeding. On behalf of the British Menopause Society (BMS) an expert review panel was established, including primary and secondary care clinicians with expertise in the management of menopause, with representatives from key related organisations, including the Royal College of Obstetricians & Gynaecologists, the British Gynaecological Cancer Society, British Society for Gynaecological Endoscopy, Royal College of General Practitioners and Faculty of Sexual and Reproductive Health, and service development partners from NHS England and GIRFT (Getting it Right First Time). For each topic, a focused literature review was completed to develop evidence led recommendations, where available, which were ratified by consensus review within the panel and by guideline groups.

Peripubertal viral-like challenge and social isolation mediate overlapping but distinct effects on behaviour and brain interferon regulatory factor 7 expression in the adult Wistar rat.

A range of adverse, early life environmental influences such as viral infection and social deprivation are thought to increase risk of psychiatric illness later in life. Here, we used peripheral administration of the viral infection mimic polyriboinosinic-polyribocytidylic acid (polyI:C) to compare the consequences of peripubertal infection and isolation rearing. Isolation rearing induced deficits in sensorimotor gating and recognition memory while no changes in social interaction or spatial learning were observed. PolyI:C injection during the peripubertal period markedly increased expression of interferon-stimulated genes (Ifit2, Prkr, Mx2 and Irf7) in the hippocampal dentate gyrus demonstrating that peripheral administration of the viral mimic in the adolescent animal does have direct effects in the brain. Peripubertal infection mimicry induced a similar but later emerging behavioural deficit in prepulse inhibition implying the existence of a peripubertal window of opportunity for viral-mediated cytokine increases to impact brain development and function. PolyI:C treatment also impaired novel object recognition but did not alter spatial reference memory or social interaction. Combining the polyI:C challenge with social isolation did not exacerbate the behavioural deficits seen with isolation rearing alone. Using Irf7 as a marker, peripubertal viral infection mimicry, isolation rearing and a combination of both were all seen to produce a long-lasting molecular imprint on the interferon-associated signalling pathway in the principal neuron population of the hippocampal dentate gyrus. The data suggest that the sensitivity of brain structure and function to disruption by viral infection extends into the peripubertal period. Moreover, augmented interferon signalling in hippocampus may represent a common molecular imprint of environmental insults associated with neuropsychiatric illnesses like schizophrenia.