Compact, Miniature MMIC Receiver Modules for an MMIC Array Spectrograph

A single-pixel prototype of a W-band detector module with a digital back-end was developed to serve as a building block for large focal-plane arrays of monolithic millimeter-wave integrated circuit (MMIC) detectors. The module uses low-noise amplifiers, diode-based mixers, and a WR10 waveguide input with a coaxial local oscillator. State-of-the-art InP HEMT (high electron mobility transistor) MMIC amplifiers at the front end provide approximately 40 dB of gain. The measured noise temperature of the module, at an ambient temperature of 300 K, was found to be as low as 450 K at 95 GHz. The modules will be used to develop multiple instruments for astrophysics radio telescopes, both on the ground and in space. The prototype is being used by Stanford University to characterize noise performance at cryogenic temperatures. The goal is to achieve a 30-50 K noise temperature around 90 GHz when cooled to a 20 K ambient temperature. Further developments include characterization of the IF in-phase (I) and quadrature (Q) signals as a function of frequency to check amplitude and phase; replacing the InP low-noise amplifiers with state-of-the-art 35-nm-gate-length NGC low-noise amplifiers; interfacing the front-end module with a digital back-end spectrometer; and developing a scheme for local oscillator and IF distribution in a future array. While this MMIC is being developed for use in radio astronomy, it has the potential for use in other industries. Applications include automotive radar (both transmitters and receivers), communication links, radar systems for collision avoidance, production monitors, ground-penetrating sensors, and wireless personal networks

Prognostic value of NT-proBNP levels in the acute phase of sepsis on lower long-term physical function and muscle strength in sepsis survivors

Background: Sepsis survivors often develop chronic critical illness (CCI) and demonstrate the persistent inflammation, immunosuppression, and catabolism syndrome predisposing them to long-term functional limitations and higher mortality. There is a need to identify biomarkers that can predict long-term worsening of physical function to be able to act early and prevent mobility loss. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a well-accepted biomarker of cardiac overload, but it has also been shown to be associated with long-term physical function decline. We explored whether NT-proBNP blood levels in the acute phase of sepsis are associated with physical function and muscle strength impairment at 6 and 12 months after sepsis onset. Methods: This is a retrospective analysis conducted in 196 sepsis patients (aged 18-86 years old) as part of the University of Florida (UF) Sepsis and Critical Illness Research Center (SCIRC) who consented to participate in the 12-month follow-up study. NT-proBNP was measured at 24 h after sepsis onset. Patients were followed to determine physical function by short physical performance battery (SPPB) test score (scale 0 to12-higher score corresponds with better physical function) and upper limb muscle strength by hand grip strength test (kilograms) at 6 and 12 months. We used a multivariate linear regression model to test an association between NT-proBNP levels, SPPB, and hand grip strength scores. Missing follow-up data or absence due to death was accounted for by using inverse probability weighting based on concurrent health performance status scores. Statistical significance was set at p ≤ 0.05. Results: After adjusting for covariates (age, gender, race, Charlson comorbidity index, APACHE II score, and presence of CCI condition), higher levels of NT-proBNP at 24 h after sepsis onset were associated with lower SPPB scores at 12 months (p < 0.05) and lower hand grip strength at 6-month (p < 0.001) and 12-month follow-up (p < 0.05). Conclusions: NT-proBNP levels during the acute phase of sepsis may be a useful indicator of higher risk of long-term impairments in physical function and muscle strength in sepsis survivors

Liver fibrosis score, physical frailty, and the risk of dementia in older adults: The Italian longitudinal study on aging

Introduction: Liver fibrosis increases progressively with aging and has been associated with poorer cognitive performance in middle-aged and older adults. We investigated the relationships between a non-invasive score for advanced liver fibrosis (non-alcoholic fatty liver disease [NAFLD] fibrosis score [NFS]) and dementia risk. We also assessed physical frailty, a common geriatric condition which is associated to dementia. We tested the joint effects of physical frailty and fibrosis on dementia incidence. Methods: A total of 1061 older adults (65 to 84 years), from the Italian Longitudinal Study on Aging, were prospectively evaluated for the risk of dementia in a period between 1992 and 2001. Liver fibrosis was defined according to the NFS. Physical frailty was assessed according to the Fried's criteria. Cox proportional hazards models were used to estimate the short- and long-term risk of overall dementia, associated to the NFS, testing the effect modifier of physical frailty status. Results: Older adults with only high NFS (F3-F4) did not exhibit a significant increased risk of overall dementia. Over 8 years of follow-up, frail older adults with high NFS had an increased risk of overall dementia (hazard ratio [HR]: 4.23; 95% confidence interval [CI]: 1.22 to 14.70, P = .023). Finally, physically frail older adults with low albumin serum levels (albumin < 4.3 g/dL) and with advanced liver fibrosis (F3-F4 NFS) compared to those with lower liver fibrosis score (F0-F2 NFS) were more likely to have a higher risk of overall dementia in a long term-period (HR: 16.42; 95% CI: 1.44 to 187.67, P = .024). Discussion: Advanced liver fibrosis (F3-F4 NFS) could be a long-term predictor for overall dementia in people with physical frailty. These findings should encourage a typical geriatric, multidisciplinary assessment which accounts also for the possible co-presence of frail condition in older adults with chronic liver disease and liver fibrosis

Dietary patterns, foods, and food groups : relation to late-life cognitive disorders

The limited efficacy of disease-modifying therapeutic strategies for mild cognitive impairment (MCI) and Alzheimer\u2019s dementia (AD) underscores the need for preventive measures to reduce the burden of late-life cognitive impairment. The aim of the present review article was to investigate the relationship among dietary patterns, foods, and food groups and late-life cognitive disorders considering the results of observational studies published in the last three years (2014-2016). In the last decade, the association between diet and cognitive function or dementia has been largely investigated. However, more recently, the National Institute on Aging-Alzheimer\u2019s Association guidelines for AD and cognitive decline due to AD pathology introduced some evidence suggesting a direct relation between diet and changes in the brain structure and activity. Several studies focused on the role of the dietary patterns on late-life cognition, with accumulating evidence that combinations of foods and nutrients into certain patterns may act synergistically to provide stronger health effects than those conferred by their individual dietary components. In particular, higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline, although the Mediterranean diet (MeDi) combines several foods, micronutrients, and macronutrients already separately proposed as potential protective factors against dementia and MCI. Moreover, also other emerging healthy dietary patterns such as the Dietary Approach to Stop Hypertension (DASH) and the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) diets were associated with slower rates of cognitive decline and significant reduction in AD rate. Furthermore, some foods or food groups traditionally considered harmful such as eggs and red meat have been partially rehabilitated, while there is still a negative correlation of cognitive functions with added sugars and trans fatty acids, nutrients also increasing the cardiovascular risk. This would suggest a genesis for the same damage for aging brain

Dietary intervention and prevention of cognitive-related outcomes in healthy older adults without cognitive dysfunction

In the last decade, the association between diet and cognitive function/dementia has been largely investigated in observational studies, while there was a lack of evidence from randomized clinical trials (RCTs) on the prevention of late-life cognitive disorders though dietary intervention in cognitively healthy older adults. In the present article, we reviewed RCTs published in the last three years (2014-2016) exploring nutritional intervention efficacy in preventing the onset of late-life cognitive disorders and dementia in cognitively healthy subjects aged over 60 years using different levels of investigation (i.e., dietary pattern changes/ medical food/nutraceutical supplementation/multidomain approach and dietary macro-and micronutrient approaches). From the included RCTs, there was moderate evidence that intervention through dietary pattern changes, medical food/nutraceutical supplementation, and multidomain approach improved specific cognitive domains or cognitive-related blood biomarkers. Moreover, there was high evidence that protein supplementation improved specific cognitive domains. For fatty acid supplementation, mainly long-chain polyunsaturated fatty acids, there was emerging evidence suggesting an impact of this approach in improving specific cognitive domains, MRI findings, and/or cognitive-related biomarkers also in selected subgroups of older subjects although some results were conflicting. Moreover, there was convincing evidence of an impact of non-flavonoid polyphenol and flavonoid supplementations in improving specific cognitive domains and/or MRI findings. Finally, there was only low evidence suggesting efficacy of intervention with homocysteine-related vitamins in improving cognitive functions, dementia incidence, or cognitive-related biomarkers in cognitively healthy older subjects

The Role of Multidimensional Prognostic Index to Identify Hospitalized Older Adults with COVID-19 Who Can Benefit from Remdesivir Treatment: An Observational, Prospective, Multicenter Study

Background: Data regarding the importance of multidimensional frailty to guide clinical decision making for remdesivir use in older patients with coronavirus disease 2019 (COVID-19) are largely unexplored. Objective: The aim of this research was to evaluate if the Multidimensional Prognostic Index (MPI), a multidimensional frailty tool based on the Comprehensive Geriatric Assessment (CGA), may help physicians in identifying older hospitalized patients affected by COVID-19 who might benefit from the use of remdesivir. Methods: This was a multicenter, prospective study of older adults hospitalized for COVID-19 in 10 European hospitals, followed-up for 90 days after hospital discharge. A standardized CGA was performed at hospital admission and the MPI was calculated, with a final score ranging between 0 (lowest mortality risk) and 1 (highest mortality risk). We assessed survival with Cox regression, and the impact of remdesivir on mortality (overall and in hospital) with propensity score analysis, stratified by MPI = 0.50. Results: Among 496 older adults hospitalized for COVID-19 (mean age 80 years, female 59.9%), 140 (28.2% of patients) were treated with remdesivir. During the 90 days of follow-up, 175 deaths were reported, 115 in hospital. Remdesivir treatment significantly reduced the risk of overall mortality (hazard ratio [HR] 0.54, 95% confidence interval CI 0.35–0.83 in the propensity score analysis) in the sample as whole. Stratifying the population, based on MPI score, the effect was observed only in less frail participants (HR 0.47, 95% CI 0.22–0.96 in propensity score analysis), but not in frailer subjects. In-hospital mortality was not influenced by remdesivir use. Conclusions: MPI could help to identify less frail older adults hospitalized for COVID-19 who could benefit more from remdesivir treatment in terms of long-term survival

Nutritional interventions in patients with Alzheimer’s disease and other late-life cognitive disorders

Given the impact of nutrition on neuroprotection largely investigated in observational studies, in the present article, we reviewed evidence from randomized clinical trials (RCTs) published in the last three years (2014-2016) exploring nutritional intervention efficacy in slowing cognitive impairment progression and achieving cognitive-related outcomes in patients aged 60 years and older with mild cognitive impairment (MCI), preclinical Alzheimer\u2019s disease (AD), prodromal AD, AD, unspecified dementia, and vascular dementia using different levels of investigation (i.e., medical food/nutraceutical supplementation/multidomain approach and dietary food/macro-and micronutrient approaches). From the reviewed RCTs, there was emerging evidence that nutritional intervention through medical food/nutraceutical supplementation (Fortasyn Connect\uae and another similar nutraceutical formulation) and multidomain approach improved magnetic resonance imaging findings and other cognitive-related biomarkers, but without clear effect on cognition in mild AD and MCI. Moreover, there was some evidence of a positive effect of antioxidant-rich foods (nuts) in improving specific cognitive domains and cognitive-related outcomes in MCI and mild-to-moderate dementia, but only in small samples. There was also convincing evidence for fatty acid supplementation, mainly n-3 polyunsaturated fatty acids (PUFAs), in improving specific cognitive domains and/or cognitive-related biomarkers in MCI and AD. Furthermore, antioxidant vitamin and trace element supplementations improved only cognitive-related outcomes and biomarkers, without effect on cognitive function in AD and MCI patients. Finally, high-dose B vitamin supplementation in AD and MCI patients improved cognitive outcomes but only in the subjects with a high baseline plasma n-3 PUFA, while folic acid supplementation had positive impact on specific cognitive domains

Sentinel lymph node biopsy versus axillary lymph node dissection in breast cancer patients undergoing mastectomy with one to two metastatic sentinel lymph nodes: sub-analysis of the SINODAR-ONE multicentre randomized clinical trial and reopening of enrolment

Background: The initial results of the SINODAR-ONE randomized clinical trial reported that patients with T1-2 breast cancer and one to two macrometastatic sentinel lymph nodes treated with breast-conserving surgery, sentinel lymph node biopsy only, and adjuvant therapy did not present worse 3-year survival, regional recurrence, or distant recurrence rates compared with those treated with axillary lymph node dissection. To extend the recommendation of axillary lymph node dissection omission even in patients treated with mastectomy, a sub-analysis of the SINODAR-ONE trial is presented here. Methods: Patients with T1-2 breast cancer and no more than two metastatic sentinel lymph nodes undergoing mastectomy were analysed. After sentinel lymph node biopsy, patients were randomly assigned to receive either axillary lymph node dissection followed by adjuvant treatment (standard arm) or adjuvant treatment alone (experimental arm). The primary endpoint was overall survival. The secondary endpoint was recurrence-free survival. Results: A total of 218 patients were treated with mastectomy; 111 were randomly assigned to the axillary lymph node dissection group and 107 to the sentinel lymph node biopsy-only group. At a median follow-up of 33.0 months, there were three deaths (two deaths in the axillary lymph node dissection group and one death in the sentinel lymph node biopsy-only group). There were five recurrences in each treatment arm. No axillary lymph node recurrence was observed. The 5-year overall survival rates were 97.8 and 98.7 per cent in the axillary lymph node dissection treatment arm and the sentinel lymph node biopsy-only treatment arm, respectively (P = 0.597). The 5-year recurrence-free survival rates were 95.7 and 94.1 per cent in the axillary lymph node dissection treatment arm and the sentinel lymph node biopsy treatment arm, respectively (P = 0.821). Conclusion: In patients with T1-2 breast cancer and one to two macrometastatic sentinel lymph nodes treated with mastectomy, the overall survival and recurrence-free survival rates of patients treated with sentinel lymph node biopsy only were not inferior to those treated with axillary lymph node dissection. To strengthen the conclusion of the trial, the enrolment of patients treated with mastectomy was reopened as a single-arm experimental study

Preservation of Axillary Lymph Nodes Compared with Complete Dissection in T1–2 Breast Cancer Patients Presenting One or Two Metastatic Sentinel Lymph Nodes: The SINODAR-ONE Multicenter Randomized Clinical Trial

Background: The SINODAR-ONE trial is a prospective noninferiority multicenter randomized study aimed at assessing the role of axillary lymph node dissection (ALND) in patients undergoing either breast-conserving surgery or mastectomy for T1–2 breast cancer (BC) and presenting one or two macrometastatic sentinel lymph nodes (SLNs). The endpoints were to evaluate whether SLN biopsy (SLNB) only was associated with worsening of the prognosis compared with ALND in terms of overall survival (OS) and relapse. Methods: Patients were randomly assigned (1:1 ratio) to either removal of ≥ 10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm). Results: The trial started in April 2015 and ceased in April 2020, involving 889 patients. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB-only arm, respectively (p = 0.936). Conclusions: The 3-year survival and relapse rates of T1–2 BC patients with one or two macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND