Room temperature "optical nanodiamond hyperpolarizer": Physics, design, and operation.

Dynamic Nuclear Polarization (DNP) is a powerful suite of techniques that deliver multifold signal enhancements in nuclear magnetic resonance (NMR) and MRI. The generated athermal spin states can also be exploited for quantum sensing and as probes for many-body physics. Typical DNP methods require the use of cryogens, large magnetic fields, and high power microwave excitation, which are expensive and unwieldy. Nanodiamond particles, rich in Nitrogen-Vacancy (NV) centers, have attracted attention as alternative DNP agents because they can potentially be optically hyperpolarized at room temperature. Here, unraveling new physics underlying an optical DNP mechanism first introduced by Ajoy et al. [Sci. Adv. 4, eaar5492 (2018)], we report the realization of a miniature "optical nanodiamond hyperpolarizer," where 13C nuclei within the diamond particles are hyperpolarized via the NV centers. The device occupies a compact footprint and operates at room temperature. Instrumental requirements are very modest: low polarizing fields, low optical and microwave irradiation powers, and convenient frequency ranges that enable miniaturization. We obtain the best reported optical 13C hyperpolarization in diamond particles exceeding 720 times of the thermal 7 T value (0.86% bulk polarization), corresponding to a ten-million-fold gain in averaging time to detect them by NMR. In addition, the hyperpolarization signal can be background-suppressed by over two-orders of magnitude, retained for multiple-minute long periods at low fields, and deployed efficiently even to 13C enriched particles. Besides applications in quantum sensing and bright-contrast MRI imaging, this work opens possibilities for low-cost room-temperature DNP platforms that relay the 13C polarization to liquids in contact with the high surface-area particles.

Hyperpolarized relaxometry based nuclear T1 noise spectroscopy in diamond.

The origins of spin lifetimes in quantum systems is a matter of importance in several areas of quantum information. Spectrally mapping spin relaxation processes provides insight into their origin and motivates methods to mitigate them. In this paper, we map nuclear relaxation in a prototypical system of [Formula: see text] nuclei in diamond coupled to Nitrogen Vacancy (NV) centers over a wide field range (1 mT-7 T). Nuclear hyperpolarization through optically pumped NV electrons allows signal measurement savings exceeding million-fold over conventional methods. Through a systematic study with varying substitutional electron (P1 center) and [Formula: see text] concentrations, we identify the operational relaxation channels for the nuclei at different fields as well as the dominant role played by [Formula: see text] coupling to the interacting P1 electronic spin bath. These results motivate quantum control techniques for dissipation engineering to boost spin lifetimes in diamond, with applications including engineered quantum memories and hyperpolarized [Formula: see text] imaging.

Wide dynamic range magnetic field cycler: Harnessing quantum control at low and high fields.

We describe the construction of a fast field cycling device capable of sweeping a 4-order-of-magnitude range of magnetic fields, from ∼1 mT to 7 T, in under 700 ms, and which is further extendable to a 1 nT-7 T range. Central to this system is a high-speed sample shuttling mechanism between a superconducting magnet and a magnetic shield, with the capability to access arbitrary fields in between with high resolution. Our instrument serves as a versatile platform to harness the inherent dichotomy of spin dynamics on offer at low and high fields-in particular, the low anisotropy, fast spin manipulation, and rapid entanglement growth at low field as well as the long spin lifetimes, spin specific control, and efficient inductive measurement possible at high fields. Exploiting these complementary capabilities in a single device opens up applications in a host of problems in quantum control, sensing, and information storage, besides in nuclear hyperpolarization, relaxometry, and imaging. In particular, in this paper, we focus on the ability of the device to enable low-field hyperpolarization of 13C nuclei in diamond via optically pumped electronic spins associated with nitrogen vacancy defect centers.

Enhanced dynamic nuclear polarization via swept microwave frequency combs.

Dynamic nuclear polarization (DNP) has enabled enormous gains in magnetic resonance signals and led to vastly accelerated NMR/MRI imaging and spectroscopy. Unlike conventional cw-techniques, DNP methods that exploit the full electron spectrum are appealing since they allow direct participation of all electrons in the hyperpolarization process. Such methods typically entail sweeps of microwave radiation over the broad electron linewidth to excite DNP but are often inefficient because the sweeps, constrained by adiabaticity requirements, are slow. In this paper, we develop a technique to overcome the DNP bottlenecks set by the slow sweeps, using a swept microwave frequency comb that increases the effective number of polarization transfer events while respecting adiabaticity constraints. This allows a multiplicative gain in DNP enhancement, scaling with the number of comb frequencies and limited only by the hyperfine-mediated electron linewidth. We demonstrate the technique for the optical hyperpolarization of 13C nuclei in powdered microdiamonds at low fields, increasing the DNP enhancement from 30 to 100 measured with respect to the thermal signal at 7T. For low concentrations of broad linewidth electron radicals [e.g., TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl)oxyl)], these multiplicative gains could exceed an order of magnitude.

No increased death toll for long-term menopausal hormone therapy.

It took many years since the initial publication of data from the Women's Health Initiative (WHI) study until further analyses and additional accumulated clinical information allowed realization of the full scope of its results. At first, the focus was on morbidity, mainly the slightly higher incidence of cardiovascular events and breast cancer cases among postmenopausal hormone users. Then, the age factor became evident, and the good safety profile of hormone therapy in healthy women initiating treatment near menopause and using it for up to 10 years eased the previous concerns. Now, 15 years after the first release of the WHI data, long-term follow-up of the WHI cohort enables consideration of mortality records as well. These data were recently summarized by the WHI investigators as follows: 'Among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.' It seems that the bitter debate on the hazards of postmenopausal hormone therapy has come to an end, since the existing database permits clear and rationalized prescribing decisions.

Menopausal hormone therapy for primary prevention: why the USPSTF is wrong.

The US Preventive Services Task Force (USPSTF) Draft Recommendation statement on Menopausal Hormone Therapy: Primary Prevention for Chronic Diseases, released in May 2017, perpetuates a major disconnect between the primary population affected, women within roughly 10 years of menopause, and the data cited. Furthermore, major elements of the evidence relied upon have been misinterpreted or misstated, particularly in regard to coronary heart disease and breast cancer, for which there is no statistically significant evidence of harm. As currently drafted, the recommendations reiterate the USPSTF statements of 2012, 2005 and 2002, and will perpetuate egregious harm to the public health. In an attempt to avoid that outcome and to facilitate a return to rational discourse regarding menopausal hormone therapy, an ad hoc group of experts in menopausal health submitted this comprehensive response to the USPSTF.

Sleep duration and midlife women's health.

Sleep is mandatory for life and therefore any sleep deprivation or disruption might carry ill-health outcomes. The optimal night's sleep duration seems to be around 7 h, as too little sleep and too much sleep have been found to be associated with a variety of changes in well-being, physical and psychological parameters. This mini-review enlightens the potential health consequences of sleep disturbance relevant to menopause and midlife women's health. These include cardiovascular and metabolic derangements, cognitive impairment, osteoporosis, and cancer-related perspectives. Still, the current knowledge suggests that, even if statistically significant associations are detected, the absolute excessive risks are relatively small or modest.

Circadian rhythm and menopause.

Circadian rhythm is an internal biological clock which initiates and monitors various physiological processes with a fixed time-related schedule. The master circadian pacemaker is located in the suprachiasmatic nucleus in the hypothalamus. The circadian clock undergoes significant changes throughout the life span, at both the physiological and molecular levels. This cyclical physiological process, which is very complex and multifactorial, may be associated with metabolic alterations, atherosclerosis, impaired cognition, mood disturbances and even development of cancer. Sex differences do exist, and the well-known sleep disturbances associated with menopause are a good example. Circadian rhythm was detected in the daily pattern of hot flushes, with a peak in the afternoons. Endogenous secretion of melatonin decreases with aging across genders, and, among women, menopause is associated with a significant reduction of melatonin levels, affecting sleep. Although it might seem that hot flushes and melatonin secretion are likely related, there are not enough data to support such a hypothesis.

Alzheimer's disease, menopause and the impact of the estrogenic environment.

Decades ago, postmenopausal hormone replacement was considered the panacea for midlife women. Prevention of the age-related cognitive decline was among the top alleged benefits of this therapy. However, the data from the Women's Health Initiative Memory Study (WHI-WHIMS) study showed the opposite, indicating worsening of several cognitive domains in hormone users. Since WHIMS recruited women who were 65 years or older, it became crucial to investigate the effects of hormone therapy in the early menopause as well. Recent studies, such as WHIMS-Young, the Kronos Early Estrogen Prevention Study and the Early versus Late Intervention Trial with Estradiol targeted the younger women, and indeed showed that hormone therapy may have positive cognitive outcomes in this age group. Whether or not hormone therapy has an effect on already demented women remains to be further explored, as data are scarce.

Withdrawal of hormone therapy and increased risk of cardiovascular disease.

Many menopause specialists follow the principle of prescribing postmenopausal hormone therapy (HT) for the shortest duration needed, in order to decrease the risk of some related serious adverse effects, such as breast cancer. Based on several large studies, it seems, however, that withdrawal of HT may be associated with immediate, though small increased risk of coronary heart disease and stroke. Cessation of HT correlates with increased risk of fractures as well. This information should be relayed to hormone users while discussing the continuation of HT with their health-care provider, but, since the potential cardiovascular harm is actually very small, it should not deter symptomatic women from using HT when needed.

Hormone therapy and large bowel cancer revisited.

Many studies have investigated potential links between postmenopausal hormone therapy (HT) and the risk for colorectal cancer. Most of these studies showed some reduction in risk, but association with the exact grade of the tumor or with cancer mortality is less consistent. Activation of estrogen receptor beta (ERß) related cellular pathways is probably the pathophysiological basis for this HT effect, since ERßs exert antiproliferative and pro-apoptotic signaling, inhibit inflammatory signaling and modulate the tumor microenvironment. To note, the impact on health may not be substantial as the absolute numbers point at the order of only a few saved cases per 10 000 women per year of hormone use.

Midlife ADHD in women: any relevance to menopause?

Recently, there has been a growing interest in better understanding of the adult-type attention deficit hyperactive disorder (ADHD). It is now accepted that many children with ADHD continue to have symptoms later in life, although the characteristics of the disease may change substantially in adults. Data are emerging on ADHD in midlife and old age and some studies analyze gender differences and co-morbidities during the lifespan of ADHD patients. This short communication discusses the possible resemblance of certain menopausal symptoms and those of adult ADHD and the potential contribution of the female hormonal environment. Further, there might be a promising role for psychostimulants, the mainstay of ADHD management, as treatment of impairment of some executive function domains in menopausal women.

Personal opinion: Treatment of vulvovaginal atrophy--are hidden interests and misinformation preventing better management?

Menopausal women very often complain of vulvovaginal atrophy (VVA)-related symptoms, which mainly include dryness, irritation, dyspareunia and pain. The ideal therapeutic approach is to use systemic or intravaginal estrogen, which has proved to be effective. However, because of safety concerns that were raised after the publication of the Women's Health Initiative data, non-estrogenic and non-hormonal therapies for VVA have been developed and heavily promoted. Many menopause specialists believe that the flow of information on the newer products indicated for VVA seems to include an inaccurate message, which downgrades the use of estrogenic preparations and upgrades modern non-estrogenic therapies. Both media and medical sources have created an atmosphere of exaggerated worries over intravaginal estrogen therapies, which are not substantiated by hard clinical facts.

White matter hyperintensities, hot flushes and estrogen--are they related?

White matter hyperintensities (WMH) are areas of high intensity observed in brain MRI scans. They are usually seen in normal aging but also in a number of neurological and psychiatric disorders. One of the underlying mechanisms is ischemia, expressed as small vessel disease. Since the volume of WMH may correlate with cognition, and an ongoing debate links postmenopausal hormone therapy with stroke and a decline in certain cognitive domains, several MRI studies have addressed this potential association. Two major randomized, placebo-controlled trials - WHIMS and KEEPS, the first including elderly women and the second recruiting recently menopausal women, did not demonstrate any safety concerns in this respect in hormone users.

Long-term menopausal hormone therapy and health consequences ­ how to choose sides?

There is no debate any more on the good safety profile of postmenopausal hormone therapy (HT) in healthy perimenopausal and early postmenopausal women, but there are still many open issues related to the consequences of long-term HT, especially in older women. A recent Cochrane meta-analysis showed that women who started HT less than 10 years after the menopause had lower mortality and coronary heart disease (CHD), but more venous thromboembolism (DVT). However, in those who started treatment more than 10 years after the menopause, there was high-quality evidence that it had little effect on death or CHD between HT and placebo groups but there was an increased risk of stroke and DVT. In contrast, many large, observational studies such as a recent one from Finland (3.3 million years of HT exposure) have shown that the risk of CHD or stroke death and all-cause mortality was significantly reduced, both in those who initiated HT below or above age 60 years. Because of conflicting data concerning long-term HT use, it seems that every health-care provider chooses as reference those studies that can support his/her individual views and therapeutic approach.

Sedentary women: sit less, live more!

Even lay persons know that a sedentary lifestyle is unhealthy. Still, the majority of people do not comply with current recommendations for physical activity. Data on the ill effects of sedentarism keep on increasing, clearly showing a significant adverse impact and increased risk for cardiovascular disease, cancer, fracture and various overweight-related metabolic conditions. The simple fact that prolonged sitting is associated with a shorter life span must be repeatedly discussed with our patients.

Deadly forecast.

Recent epidemiological studies from various countries point at the mounting incidence of cancer. This continuous increase in the number of cancer cases will keep its pace in the future. The lifetime risk of cancer for people born since 1960 is forecast to be more than 50%. Thus cancer becomes the major health problem, and policy-makers should plan ahead how to implement effective prevention programs, on the one hand, and optimize the strategy for better diagnosis, treatment and surveillance of cancer patients on the other hand.

Microbiotica in women.

The perception that certain body cavities and spaces that are heavily inhabited by micro-organisms should be regarded as 'external' to the body function is no longer valid. Extensive research during recent years has demonstrated the importance of those microbes to normal physiology, which means that the human body and those tiny organisms are actually symbiotic. The major point of interaction between the human body and the microbiome is the gut. There are also gender-specific aspects for this symbiosis: bacterial vaginosis has serious implications for female morbidity, including reports of pelvic inflammatory disease, adverse pregnancy outcomes, increased susceptibility to sexually transmitted infections and infertility. Re-establishing a normal flora might be beneficial and therefore the use of probiotics and re-colonization by 'healthy' bacteria have become very popular. Probiotics may serve as an adjunct for treating recurrences of urogenital infections and vaginal atrophy. Some animal studies have pointed at potential beneficial effects of Lactobacilli species on bone health.

Patient information leaflets: friend or foe?

Every registered medication has an information insert in its package. This patient leaflet provides information on the product, which includes clinical pharmacology, recommended dose, mode of administration, how supplied, and a large section contains warnings and contraindications, adverse reactions, and precautions. Most of the prescribers do not read the patient information leaflets and do not discuss it with the users, whereas some patients do read it thoroughly. This may create worries and uncertainties resulting in reduced compliance to treatment. With easy access of patients to information on drugs that they use, mainly through the electronic media, it is very important that the text and contents of these patient leaflets are simple to understand and readable. Although information from official health agencies is superior to net-based sources, the patient information leaflets should be improved and become more user-friendly and less frightening.