Broad Diversity of Near-Infrared Single-Photon Emitters in Silicon.

We report the detection of individual emitters in silicon belonging to seven different families of optically active point defects. These fluorescent centers are created by carbon implantation of a commercial silicon-on-insulator wafer usually employed for integrated photonics. Single photon emission is demonstrated over the 1.1-1.55 µm range, spanning the O and C telecom bands. We analyze their photoluminescence spectra, dipolar emissions, and optical relaxation dynamics at 10 K. For a specific family, we show a constant emission intensity at saturation from 10 K to temperatures well above the 77 K liquid nitrogen temperature. Given the advanced control over nanofabrication and integration in silicon, these individual artificial atoms are promising systems to investigate for Si-based quantum technologies.

Robotic Arm-assisted versus Manual (ROAM) total knee arthroplasty: a randomized controlled trial.

Aims: The primary aim was to assess whether robotic total knee arthroplasty (rTKA) had a greater early knee-specific outcome when compared to manual TKA (mTKA). Secondary aims were to assess whether rTKA was associated with improved expectation fulfilment, health-related quality of life (HRQoL), and patient satisfaction when compared to mTKA. Methods: A randomized controlled trial was undertaken, and patients were randomized to either mTKA or rTKA. The primary objective was functional improvement at six months. Overall, 100 patients were randomized, 50 to each group, of whom 46 rTKA and 41 mTKA patients were available for review at six months following surgery. There were no differences between the two groups. Results: There was no difference between rTKA and mTKA groups at six months according to the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) functional score (mean difference (MD) 3.8 (95% confidence interval (CI) -5.6 to 13.1); p = 0.425). There was a greater improvement in the WOMAC pain score at two months (MD 9.5 (95% CI 0.6 to 18.3); p = 0.037) in the rTKA group, although by six months no significant difference was observed (MD 6.7 (95% CI -3.6 to 17.1); p = 0.198). The rTKA group were more likely to achieve a minimal important change in their WOMAC pain score when compared to the mTKA group at two months (n = 36 (78.3%) vs n = 24 (58.5%); p = 0.047) and at six months (n = 40 (87.0%) vs n = 29 (68.3%); p = 0.036). There was no difference in satisfaction between the rTKA group (97.8%; n = 45/46) and the mTKA group (87.8%; n = 36/41) at six months (p = 0.096). There were no differences in EuroQol five-dimension questionnaire (EQ-5D) utility gain (p ≥ 0.389) or fulfilment of patient expectation (p ≥ 0.054) between the groups. Conclusion: There were no statistically significant or clinically meaningful differences in the change in WOMAC function between mTKA and rTKA at six months. rTKA was associated with a higher likelihood of achieving a clinically important change in knee pain at two and six months, but no differences in knee-specific function, patient satisfaction, health-related quality of life, or expectation fulfilment were observed.

Increasing age does not influence hip-specific functional outcome or health-related quality of life following total hip arthroplasty : a five-year prospective cohort study.

AIMS: The primary aim of our study was to assess the influence of age on hip-specific outcome following total hip arthroplasty (THA). Secondary aims were to assess health-related quality of life (HRQoL) and level of activity according to age. METHODS: A prospective cohort study was conducted. All patients were fitted with an Exeter stem with a 32 mm head on highly cross-linked polyethylene (X3RimFit) cemented acetabulum. Patients were recruited into three age groups: < 65 years, 65 to 74 years, and ≥ 75 years, and assessed preoperatively and at three, 12, 24, and 60 months postoperatively. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), and Hip disability and Osteoarthritis Outcome Score (HOOS), were used to assess hip-specific outcome. EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and 36-Item Short Form Survey (SF-36) scores were used to assess HRQoL. The Lower Extremity Activity Scale (LEAS) and Timed Up and Go (TUG) were used to assess level of activity. RESULTS: There were no significant (p > 0.05) differences in the WOMAC scores, HSS, HOOS, or EQ-5D-5L at any postoperative timepoint between the age groups. Patients aged ≥ 75 years had significantly lower physical function (p ≤ 0.010) and physical role (p ≤ 0.047) SF-36 scores at 12, 24, and 60 months, but were equal to that expect of an age-matched population. No differences according to age were observed for the other six domains of the SF-36 (p > 0.060). The ≥ 75 years group had a lower LEAS (p < 0.001) and longer TUG test times (p ≤ 0.032) compared to the < 65 years group, but older age groups had significant (p < 0.001) improvement relative to their preoperative baseline measures. CONCLUSION: Age did not influence postoperative hip-specific outcome or HRQoL (according to the EQ-5D) following THA. Despite a significant improvement, older patients had lower postoperative activity levels compared to younger patients, but this may be reflective of the overall physical effect of ageing.Cite this article: Bone Jt Open 2022;3(9):692-700.

Robotic- and orthosensor-assisted versus manual (ROAM) total knee replacement: a study protocol for a randomised controlled trial.

BACKGROUND: Robotic-arm-assisted knee arthroplasty allows for more accurate component positioning and alignment and is associated with better patient-reported outcomes compared to manually performed jig-based knee arthroplasty. However, what is not known is whether the addition of an intra-articular sensor (VerasenseTM) to aid intraoperative balancing of the total knee replacement (TKR) offers improved functional outcomes for the patient. The purpose of this research is to compare the outcomes of patients undergoing a conventional manual knee replacement to those undergoing TKR using robotic-assisted surgery and the VerasenseTM to optimise alignment and balance the knee joint, respectively, and assess the associated cost economics of such technology. METHODS AND ANALYSIS: This randomised controlled trial will include 90 patients with end-stage osteoarthritis of the knee undergoing primary TKR. Patients meeting the inclusion/exclusion criteria that consent to be in the study will be randomised at a ratio of 1:1 to either manual TKR (standard of care) or robotic-arm-assisted TKR with VerasenseTM to aid balancing of the knee. The primary objective will be functional improvement at 6 months following surgery between the two groups. The secondary objectives are to compare changes in knee-specific function, joint awareness, patient expectation and fulfilment, satisfaction, pain, stiffness and functional ability, health-related quality of life, cost-effectiveness, and gait patterns between the two groups. Ethical approval was obtained by the Tyne & Wear South Research Ethics Committee, UK. The study is sponsored by the Newcastle Hospitals NHS Foundation Trust. DISCUSSION: This study will assess whether the improved accuracy of component positioning using the robotic-arm-assisted surgery and the VerasenseTM to aid balancing of the TKR offers improved outcome relative to standard manual jig-based systems that are currently the standard of care. This will be assessed primarily according to knee-specific function, but several other measures will also be assessed including whether these are cost-effective interventions. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ISRCTN47889316 https://doi.org/10.1186/ISRCTN47889316 . Registered on 25 November 2019 DATE AND VERSION FOR PROTOCOL: ROAM Protocol V1.0 (13-12-2018).

Brain processing of capsaicin-induced secondary hyperalgesia: a functional MRI study.

OBJECTIVE: To investigate, using functional MRI (fMRI), the neural network that is activated by the pain component of capsaicin-induced secondary mechanical hyperalgesia. BACKGROUND: Mechanical hyperalgesia (i.e., pain to innocuous tactile stimuli) is a distressing symptom of neuropathic pain syndromes. Animal experiments suggest that alterations in central pain processing occur that render tactile stimuli capable of activating central pain-signaling neurons. A similar central sensitization can be produced experimentally with capsaicin. METHODS: In nine healthy individuals the cerebral activation pattern resulting from cutaneous nonpainful mechanical stimulation at the dominant forearm was imaged using fMRI. Capsaicin was injected adjacent to the stimulation site to induce secondary mechanical hyperalgesia. The identical mechanical stimulation was then perceived as painful without changing the stimulus intensity and location. Both activation patterns were compared to isolate the specific pain-related component of mechanical hyperalgesia from the tactile component. RESULTS: The pattern during nonpainful mechanical stimulation included contralateral primary sensory cortex (SI) and bilateral secondary sensory cortex (SII) activity. During hyperalgesia, significantly higher activation was found in the contralateral prefrontal cortex: the middle (Brodmann areas [BAs] 6, 8, and 9) and inferior frontal gyrus (BAs 44 and 45). No change was present within SI, SII, and the anterior cingulate cortex. CONCLUSIONS: Prefrontal activation is interpreted as a consequence of attention, cognitive evaluation, and planning of motor behavior in response to pain. The lack of activation of the anterior cingulate contrasts with physiologic pain after C-nociceptor stimulation. It might indicate differences in the processing of hyperalgesia and C-nociceptor pain or it might be due to habituation of affective sensations during hyperalgesia compared with acute capsaicin pain.

How low can you get?

Since the early 1960s the side effects of oral contraceptives have been known to be related to the high doses (50 micro g) of ethinyl estradiol used. Research has focused on reducing the dose of both the estrogen and progestin components to reduce these side effects. While reducing the dose of both components, the contraceptive efficacy has to be maintained so as to retain a satisfactory Pearl index. These requirements appear to have been attained with 24-day regimen of a low-dose pill (15 microg of ethinyl estradiol and 60 microg of gestedone) as one part of an open-label noncomparative multicenter study. This paper reports our unit's results, which indicate that the low-dose pill promises to reduce contraceptive-related side effects, to encourage better compliance, and as corollary, to retain a satisfactory Pearl index.

Carotid artery wall changes in estrogen-treated and -untreated postmenopausal women.

OBJECTIVE: To investigate whether the thickness of the layers of the carotid artery (externa, media, and intima) are affected by menopause and its treatment with hormone replacement therapy (HRT). METHODS: One hundred twenty-nine postmenopausal women were recruited sequentially and classified into three groups. Forty-six were taking oral HRT, 32 had estradiol implants, and 51 had never taken HRT. The three layers of the externa wall of the carotid artery were identified and measured by high-resolution ultrasound. RESULTS: Women with implants had thicker carotid artery wall measurements (0.84 +/- 0.26 mm) than the other groups. The media (0.32 +/- 0.11 mm) was significantly thicker in the implant group. This layer has a high connective tissue component, including collagen type I, collagen type III, and elastin fibers. The intima layer was thinner (0.25 +/- 0.09 mm) in the oral HRT group compared with controls (0.29 +/- 0.1 mm). A statistically significant higher intima-media ratio (1.17 +/- 0.05) was calculated for the control group, compared with both the oral HRT (0.92 +/- 0.04) and implant groups (0.94 +/- 0.03). CONCLUSION: Our findings suggest that HRT given to postmenopausal women influences differentially the layers of the carotid artery. Hormones seem to encourage thickening of the layers with the highest connective tissue component (externa and media) and to delay thickening of the atheromatous intima layer. These effects on the vascular system may be partly responsible for the cardioprotection attributed to HRT.

Activation of the somatosensory cortex during Abeta-fiber mediated hyperalgesia. A MSI study.

OBJECTIVE: To investigate the neural activation in the primary somatosensory cortex (SI) that is induced by capsaicin-evoked secondary Abeta-fiber-mediated hyperalgesia with magnetic source imaging (MSI) in healthy humans. BACKGROUND: Dynamic mechanical hyperalgesia, i.e. pain to innocuous light touching, is a symptom of painful neuropathies. Animal experiments suggest that alterations in central pain processing occur so that tactile stimuli conveyed in Abeta low threshold mechanoreceptive afferents become capable of activating central pain signalling neurons. A similar state of central sensitization can be experimentally produced with capsaicin. METHODS: In six individuals the somatosensory evoked magnetic fields (SEFs) induced by non-painful electrical stimulation of Abeta-afferents at the forearm skin were recorded. Capsaicin was injected adjacent to the stimulation site to induce secondary dynamic Abeta-hyperalgesia. Thereafter, the SEFs induced by the identical electrical stimulus applied within the secondary hyperalgesic skin were analyzed. The electrical stimulus was subsequently perceived as painful without changing the stimulus intensity and location. Latencies, anatomical source location and amplitudes of SEFs during both conditions were compared. RESULTS: Non-painful electrical stimulation of Abeta-afferents induced SEFs in SI at latencies between 20 and 150 ms. Stimulation of Abeta-afferents within the capsaicin-induced secondary hyperalgesic skin induced SEFs at identical latencies and locations as compared with the stimulation of Abeta-afferents within normal skin. The amplitudes, i.e., the magnetic dipole strengths of the SEFs were higher during Abeta-hyperalgesia. CONCLUSIONS: Acute application of capsaicin produces an increase in the excitability of central neurons, e.g., in SI. This might be due to sensitization of central neurons so that normally innocuous stimuli activate pain signalling neurons or cortical neurons might increase their receptive fields.

MR imaging of tuberous sclerosis in neonates and young infants.

BACKGROUND AND PURPOSE: The MR imaging appearance of intracranial manifestations in tuberous sclerosis varies with age. The aim of this study was to specify MR characteristics in a coherent group of neonates and infants in order to distinguish them from the mature pattern. METHODS: The MR studies of seven patients under 3 months old were reviewed retrospectively. Imaging appearance, number, and distribution of tubers, white matter anomalies, subependymal nodules, and subependymal giant cell astrocytomas were analyzed. RESULTS: All patients had more white matter anomalies, subependymal nodules, subependymal giant cell astrocytomas, transmantle dysplasias, and left-hemispheric and temporal lesions, but less cortical tubers than did older patients in previous series. The lesions were easy to detect as hyperintense foci on T1-weighted images. Visibility as hypointensities on T2-weighted images was comparatively poor. CONCLUSION: The nodular subependymal and linear parenchymal tuberous sclerosis lesions in infants under 3 months old are hyperintense on T1-weighted images and hypointense on T2-weighted images as opposed to the reverse pattern of signal intensity in older persons. The scarce myelination helps to identify white matter anomalies, which become less visible as myelination progresses. Conversely, purely intracortical tubers are more difficult to diagnose in infants. Because the overall number and conspicuity of all other lesions in our series were greater than in previous series with older subjects, our findings indicate that infant age does not compromise, but facilitates, the correct MR diagnosis of tuberous sclerosis. Therefore, if tuberous sclerosis is clinically suspected within the first 3 months of life, imaging should not be delayed.

Carotid artery wall thickness in women treated with hormone replacement therapy.

OBJECTIVE: To measure the thickness of the individual layers (externa, media, intima) of the carotid artery in two groups of postmenopausal women. METHODS: A high resolution ultrasound (25-MHz Osteoson DIII Minhorst) was used to assess the distal end of the common carotid artery. Forty-six women were on hormone replacement therapy (Premarin 0.625 mg and Norgestrel 1 mg) for more than 1 year. The measurements of the treated group were compared to those of 51 postmenopausal women who acted as controls. RESULTS: No significant difference between the externa and media layers of both groups of women were noted. The media showed a tendency to be thicker in the treated group. The intima of the untreated group was found to be significantly thicker than that of the treated group (P < 0.05). Significant correlations were found between the layers of the carotid artery especially between the externa and media both mainly composed of connective tissue (Collagen Type I and III and elastin). The media/intima ratio of the treated women was significantly higher than that of the untreated group (P< 0.003). CONCLUSION: It is postulated that the changes observed may be due to the effect of oestrogen on connective tissue. These arterial changes induced by hormone replacement therapy may partially explain the cardioprotective effect this treatment has on postmenopausal women. The increased intimal thickness in untreated women compared to treated ones on the other hand would represent the reduction in atheromatous plaque formation in women on oestrogen replacement therapy.

Changes in bone collagen markers and in bone density in hormone treated and untreated postmenopausal women.

OBJECTIVE: This study aims to compare bone mineral density measurements (BMD), pyridinium crosslink levels and pyridinium crosslink levels in untreated and hormone treated postmenopausal women. METHODS: A cross-sectional study comparing biophysical (BMD) and biochemical (pyridinium crosslink and PCICP) parameters in a group of untreated postmenopausal women (n = 145) to a group of postmenopausal women on hormone replacement therapy (HRT) (n = 92). RESULTS: Untreated postmenopausal women compared to postmenopausal women on HRT had higher Osteoblastic and Osteoclastic activity. Procollagen I C-end terminal peptide (PCICP) was 11.3% lower in the women on HRT compared to controls whilst crosslinks were 27.2% lower than in controls. This seems to indicate that women on HRT had a bone balance that was higher compared to the control group (15.9%). The difference in bone density of L2-L4 between the two groups was (16.1%). CONCLUSIONS: This study seems to indicate that postmenopausal women receiving HRT readjust their bone remodelling so that although osteoblastic function is reduced, there is a much greater deduction in osteoclastic function and this results in an overall higher bone mass observed in the BMD of women on HRT.

Thrombocytopenic thrombotic purpura: severe clinic with no CT, minor MRI, but a SPECT correlate.

A 28-year-old woman with primarily therapy refractory TTP was followed neuroradiologically over 6 months. Despite pronounced neurological and neuropsychiatric symptoms including hemiparesis and aphasia she had unremarkable CT scans on two occasions. Three MRI exams showed no correlate for her neurological symptoms except a small petechial cortical hemorrhage in the right parietooccipital gyrus which may account for her TTP-related anxiety disorder. A cerebral HMPAO-SPECT showed long-standing right-sided hypoperfusion compatible with residual vasculature changes. The possible causes for the clinico-neuroradiological discrepancies are discussed in view of the literature.

Increased reduction in bone density and skin thickness in postmenopausal women on long-term corticosteroid therapy. A suggested role for estrogen add back therapy.

BACKGROUND: Long term steroid therapy is complicated by osteoporosis and generalised thinning of the skin. These two complications of long term corticosteroid therapy were routinely assessed at the Menopause Clinic of St. Luke's Hospital, Medical School, University of Malta. METHODS: A cross sectional study was performed on 64 postmenopausal women who had been on long term corticosteroids. Each woman had her skin thickness measured using high resolution ultrasound (22 mhz) and their bone density measured using a DEXA Norland. These measurements were compared to a control group (n = 557), a group of women who had sustained osteoporotic fractures (n = 180), and a group of women on hormone replacement therapy (HRT) (n = 399). A longitudinal study on 29 postmenopausal women on corticosteroids was also performed. In this study results were compared between women who in addition to their corticosteroids were on HRT and those who were on corticosteroids alone. RESULTS: The cross sectional study showed the corticosteroid therapy was associated with the thinnest skin thickness measurements mean 0.83 mm. Similarly, low bone density measurements lumbar spine mean 0.81 g/cm2 and left hip mean 0.71 g/cm2 were obtained for this group. The skin thickness in controls and in the HRT groups had a mean thickness of 0.93 mm while that of the osteoporotic fracture group was 0.88 mm. The bone density of the osteoporotic fractures in the fracture group was similar to that of group of women on long term corticosteroids. The lumbar spine had a mean density of 0.81 g/cm2 and left hip that of 0.71 g/cm2. The bone density of the control group and HRT group was significantly higher. The lumbar spine had a mean density of 0.93 g/cm2 and that of left hip was 0.82 g/cm2. The small longitudinal study compared postmenopausal women on long term corticosteroid therapy on HRT to another group who was not on HRT. The longitudinal study over four years revealed a constant increase in skin thickness (mean 6% per year) and bone density (left hip mean 5% per year, lumbar spine mean 5% per year). CONCLUSION: In postmenopausal women on long term corticosteroids, skin thickness and bone density were both decreased, but the addition of HRT as add back improved the situation dramatically. Skin thickness and bone density level in women on long term corticosteroids were comparable to that of women who had sustained osteoporotic fractures. It is therefore suggested that HRT be used as add back therapy in postmenopausal women on long term corticosteroid therapy.

Estrogens and the intervertebral disc.

Intervertebral discs are an integral part of the vertebral column. It has been shown that menopause has a negative effect on bone and on intervertebral discs. Estrogen has a beneficial effect of preserving the health of collagen-containing tissues, including the intervertebral disc. The intervertebral disc allows for mobility of the spine, and maintains a uniform stress distribution of the area of the vertebral endplates. Also, the disc influences spinal height. The disc tissue is adapted for this biomechanical function. The function of the spine is impaired if there is a loss of disc tissue. Narrowing of the disc space due to degeneration of intervertebral discs is associated with a significantly increased risk of vertebral fractures. Estrogen should be seen as the first-choice therapy for bones and other collagen-rich tissues, such as intervertebral discs, because it maintains homeostasis of the bone-remodelling unit. Unlike bisphosphonates, estrogen is unique in its ability to regenerate bone collagen after its disintegration, apart from suppressing osteoclastic activity. Besides, there is insufficient data on deterioration in bone qualities and micro-cracks in patients on long-term bisphosphonates.

Low intervertebral disc height in postmenopausal women with osteoporotic vertebral fractures compared to hormone-treated and untreated postmenopausal women and premenopausal women without fractures.

OBJECTIVE: To assess the intervertebral disc height in postmenopausal women with osteoporotic vertebral fractures. METHODS: A total of 203 women were recruited from a bone densitometer directory. The disc heights measured were those between the 12th thoracic and 3rd lumbar vertebrae. The discs were assigned the symbols D, whereby D(1) refers to the disc between the 12th thoracic and 1st lumbar vertebrae. The disc height of the group of women (n = 38) with osteoporotic vertebral fractures was compared to the disc heights of hormone-treated women (n = 47), untreated postmenopausal women (n = 77) and another group of premenopausal women (n = 41). RESULTS: The total disc height (D(1) - D(3)) (mean +/- standard deviation) in the fracture group was 1.58 +/- 0.1 cm, significantly lower (p < 0.0001) than in the untreated group (1.82 +/- 0.06 cm), which in turn was significantly (p < 0.0001) lower than in the hormone-treated group (2.15 +/- 0.08 cm) and in the premenopausal group (2.01 +/- 0.09 cm). CONCLUSION: The fracture group was noted to have the lowest intervertebral disc height compared to the other three groups. The hormone-treated and the premenopausal women had the highest disc heights recorded. These results may be due to the effect that the menopause and senescence have on the discal connective tissue components. This may lead to loss of the shock-absorbing properties of the intervertebral disc and an altered discoid shape, influencing the occurrence of osteoporotic vertebral body fractures.

The skin, carotid and intervertebral disc: making the connection!

A fairly consistent finding in work on the menopause and hormone replacement therapy is the positive effect of estrogen on connective tissue and its turnover. The menopause has been shown repeatedly to have a negative effect on the connective tissue in the dermis of the skin. Such an effect is prevented and in some cases reversed with estrogen therapy. This is similar to what happens in bone matrix. Similarly, the media in the carotid has been shown to undergo the same change with the menopause and with estrogen therapy as the dermis. The carotid artery media is increased in menopausal women on estrogen therapy and is thinner in untreated women. Recently, new information has revealed that the menopause, i.e. estrogen deprivation, has similar effects on the connective tissue of intervertebral discs. In aged intervertebral discs, the predominant collagen is type III, not type I, which is the predominant collagen in skin and bone, although skin has additional type III. These negative changes are once again prevented or reversed with estrogen therapy. This effect probably also extends to the extracellular non-collagenous matrix in all these systems, i.e. skin, carotid and intervertebral discs. The common thread is that estrogen has profound effects on connective tissue turnover, no matter the site. This has far-reaching implications not only in maintaining the structure and aesthetic appearance of tissue, but also the strength and stiffness of various tissues and the functioning of neighboring and surrounding organs.