Experimental quantum speed-up in reinforcement learning agents.

As the field of artificial intelligence advances, the demand for algorithms that can learn quickly and efficiently increases. An important paradigm within artificial intelligence is reinforcement learning1, where decision-making entities called agents interact with environments and learn by updating their behaviour on the basis of the obtained feedback. The crucial question for practical applications is how fast agents learn2. Although various studies have made use of quantum mechanics to speed up the agent's decision-making process3,4, a reduction in learning time has not yet been demonstrated. Here we present a reinforcement learning experiment in which the learning process of an agent is sped up by using a quantum communication channel with the environment. We further show that combining this scenario with classical communication enables the evaluation of this improvement and allows optimal control of the learning progress. We implement this learning protocol on a compact and fully tunable integrated nanophotonic processor. The device interfaces with telecommunication-wavelength photons and features a fast active-feedback mechanism, demonstrating the agent's systematic quantum advantage in a setup that could readily be integrated within future large-scale quantum communication networks.

Experimental demonstration of memory-enhanced quantum communication.

The ability to communicate quantum information over long distances is of central importance in quantum science and engineering1. Although some applications of quantum communication such as secure quantum key distribution2,3 are already being successfully deployed4-7, their range is currently limited by photon losses and cannot be extended using straightforward measure-and-repeat strategies without compromising unconditional security8. Alternatively, quantum repeaters9, which utilize intermediate quantum memory nodes and error correction techniques, can extend the range of quantum channels. However, their implementation remains an outstanding challenge10-16, requiring a combination of efficient and high-fidelity quantum memories, gate operations, and measurements. Here we use a single solid-state spin memory integrated in a nanophotonic diamond resonator17-19 to implement asynchronous photonic Bell-state measurements, which are a key component of quantum repeaters. In a proof-of-principle experiment, we demonstrate high-fidelity operation that effectively enables quantum communication at a rate that surpasses the ideal loss-equivalent direct-transmission method while operating at megahertz clock speeds. These results represent a crucial step towards practical quantum repeaters and large-scale quantum networks20,21.

Bright nanowire single photon source based on SiV centers in diamond.

The practical implementation of many quantum technologies relies on the development of robust and bright single photon sources that operate at room temperature. The negatively charged silicon-vacancy (SiV-) color center in diamond is a possible candidate for such a single photon source. However, due to the high refraction index mismatch to air, color centers in diamond typically exhibit low photon out-coupling. An additional shortcoming is due to the random localization of native defects in the diamond sample. Here we demonstrate deterministic implantation of Si ions with high conversion efficiency to single SiV- centers, targeted to fabricated nanowires. The co-localization of single SiV- centers with the nanostructures yields a ten times higher light coupling efficiency than for single SiV- centers in bulk diamond. This enhanced photon out-coupling, together with the intrinsic scalability of the SiV- creation method, enables a new class of devices for integrated photonics and quantum science.

Circulating Interleukin-6 Is Associated with Skeletal Muscle Strength, Quality, and Functional Adaptation with Exercise Training in Mobility-Limited Older Adults.

BACKGROUND: Human aging is characterized by a chronic, low-grade inflammation suspected to contribute to reductions in skeletal muscle size, strength, and function. Inflammatory cytokines, such as interleukin-6 (IL-6), may play a role in the reduced skeletal muscle adaptive response seen in older individuals. OBJECTIVES: To investigate relationships between circulating IL-6, skeletal muscle health and exercise adaptation in mobility-limited older adults. DESIGN: Randomized controlled trial. SETTING: Exercise laboratory on the Health Sciences campus of an urban university. PARTICIPANTS: 99 mobility-limited (Short Physical Performance Battery (SPPB) ≤9) older adults. INTERVENTION: 6-month structured physical activity with or without a protein and vitamin D nutritional supplement. MEASUREMENTS: Circulating IL-6, skeletal muscle size, composition (percent normal density muscle tissue), strength, power, and specific force (strength/CSA) as well as physical function (gait speed, stair climb time, SPPB-score) were measured pre- and post-intervention. RESULTS: At baseline, Spearman's correlations demonstrated an inverse relationship (P<0.05) between circulating IL-6 and thigh muscle composition (r = -0.201), strength (r = -0.311), power (r = -0.210), and specific force (r = -0.248), and positive association between IL-6 and stair climb time (r = 0.256; P<0.05). Although the training program did not affect circulating IL-6 levels (P=0.69), reductions in IL-6 were associated with gait speed improvements (r = -0.487; P<0.05) in "higher" IL-6 individuals (>1.36 pg/ml). Moreover, baseline IL-6 was inversely associated (P<0.05) with gains in appendicular lean mass and improvements in SPPB score (r = -0.211 and -0.237, respectively). CONCLUSIONS: These findings implicate age-related increases in circulating IL-6 as an important contributor to declines in skeletal muscle strength, quality, function, and training-mediated adaptation. Given the pervasive nature of inflammation among older adults, novel therapeutic strategies to reduce IL-6 as a means of preserving skeletal muscle health are enticing.

Lower-Extremity Torque Capacity and Physical Function in Mobility-Limited Older Adults.

OBJECTIVES: Skeletal muscle weakness and an increase in fatigability independently contribute to age-related functional decline. The objective of this study was to examine the combined contribution of these deficiencies (i.e., torque capacity) to physical function, and then to assess the functional implications of progressive resistance training (PRT) mediated-torque capacity improvements in mobility-limited older adults. DESIGN: Randomized controlled trial. SETTING: Exercise laboratory on the Health Sciences campus of an urban university. PARTICIPANTS: Seventy mobility-limited (Short Physical Performance Battery (SPPB) ≤9) older adults (~79 yrs). INTERVENTION: Progressive resistance training or home-based flexibility 3 days/week for 12 weeks. MEASUREMENTS: Torque capacity was defined as the sum of peak torques from an isokinetic knee extension fatigue test. Relationships between torque capacity and performance-based and patient-reported functional measures before and after PRT were examined using partial correlations adjusted for age, sex, and body mass index. RESULTS: Torque capacity explained (P<0.05) 10 and 28% of the variance in six-minute walk distance and stair climb time, respectively. PRT-mediated torque capacity improvements were paralleled by increases (P<0.05) in self-reported activity participation (+20%) and advanced lower extremity function (+7%), and associated (P<0.05) with a reduction in activity limitations (r=0.44) and an improved SPPB score (r=0.32). CONCLUSION: Skeletal muscle torque capacity, a composite of strength and fatigue, may be a proximal determinant of physical function in mobility-limited older individuals. To more closely replicate the musculoskeletal demands of real-life tasks, future studies are encouraged to consider the combined interaction of distinct skeletal muscle faculties to overall functional ability in older adults.

Broadband loop gap resonator for nitrogen vacancy centers in diamond.

We present an S-band tunable loop gap resonator (LGR), which provides strong, homogeneous, and directionally uniform broadband microwave (MW) drive for nitrogen-vacancy (NV) ensembles. With 42 dBm of input power, the composite device provides drive field amplitudes approaching 5 G over a circular area ≳50 mm2 or cylindrical volume ≳250 mm3. The wide 80 MHz device bandwidth allows driving all NV Zeeman resonances for bias magnetic fields below 20 G. The device realizes percent-scale MW drive inhomogeneity; we measure a fractional root-mean-square inhomogeneity σ rms = 1.6% and a peak-to-peak variation σ pp = 3% over a circular area of 11 mm2 and σ rms = 3.2% and σ pp = 10.5% over a larger 32 mm2 circular area. We demonstrate incident MW power coupling to the LGR using two methodologies: a printed circuit board-fabricated exciter antenna for deployed compact bulk sensors and an inductive coupling coil suitable for microscope-style imaging. The inductive coupling coil allows for approximately 2π steradian combined optical access above and below the device, ideal for envisioned and existing NV imaging and bulk sensing applications.

The families of borderlines. A comparative study.

The families of 12 carefully diagnosed patients with borderline personality disorder are compared with the families of both paranoid schizophrenic patients and patients with neurotic personality disorders. The families of the borderline patients were distinguished by the rigid tightness of the marital bond to the exclusion of the attention, support, or protection of the children. This pattern of neglect conforms to one theme in the clinical literature, and its implications for understanding and treating borderline patients are discussed. Limitations in the research methodology make the conclusions from this study tentative, but the results suggest new areas in need of research attention.

Comparison of the safety and efficacy of nabumetone and aspirin in the treatment of osteoarthritis in adults.

A six-month, multicenter, double-blind study compared the efficacy and safety of two therapeutic regimens in 332 patients with osteoarthritis. The patients received either 1,000 mg of nabumetone as a single bedtime dose or 900 mg of aspirin in four divided doses. At the end of the study, patients in both treatment groups showed significant improvement from baseline for all five parameters; no statistically or clinically significant differences were observed between the groups. The safety data did reveal clinically and statistically significant differences between the groups. Aspirin-treated patients experienced a greater frequency of withdrawal from the study because of adverse experiences (34 percent versus 13 percent), a greater incidence of having at least one treatment-related adverse experience (73 percent versus 52 percent), a greater percentage of patients with at least one moderate or severe treatment-related adverse experience (47 percent versus 22 percent), and a greater percentage of patients with treatment-related adverse experiences affecting the gastrointestinal system (43 percent versus 32 percent) or the inner ear (32 percent versus 10 percent). The results of this study demonstrated that nabumetone, 1,000 mg at bedtime, is as efficacious as aspirin, 900 mg four times daily, produces fewer adverse effects, and is indicated in the treatment of osteoarthritis.

Plasma oestriol following vaginal administration: morning versus evening insertion and influence of food.

The aim of this trial was to study the vaginal absorption of oestriol and to investigate whether morning rather than evening oestriol administration would produce different plasma oestriol patterns. The influence of food intake on plasma oestriol levels was also investigated. Nine post-menopausal women were given 0.5 mg oestriol (ovula supplied by Leo AB, Sweden) intravaginally every evening for 16 days. Thereafter, 1 mg oestriol was given every evening for another 5 days, except on treatment days 18 and 19 when 1 mg oestriol was given in the morning instead. Venous blood samples were collected at frequent intervals on day 19 (morning administration) and a meal was allowed 4 h later. On the day 21 (evening administration), venous blood samples were taken at frequent intervals during the night and no meal was given until the next morning. Plasma concentrations of unconjugated oestriol were measured by means of a specific radioimmunoassay (RIA). A difference was seen in the plasma oestriol patterns when the results following morning and evening administration were compared. However, no significant difference as regards the total 24-h systemic availability of oestriol was observed. A minimal increase in plasma oestriol levels was seen after a meal in the case of both morning and evening intravaginal oestriol administration, possibly as a result of enterohepatic recirculation.

Effects of vaginally-administered oestriol on post-menopausal urogenital disorders: a cytohormonal study.

Forty post-menopausal women with urogenital disorders who were inpatients in the same geriatric hospital were treated with oestriol (E3) for 6 weeks. For the first 2 weeks 0.5 mg E3 (Leo AB, Sweden) was administered intravaginally every day. Over the following 4 weeks the patients received the same quantity either once or twice weekly as a maintenance dose. Oestrogen influence on the vaginal and urethral epithelium was assessed by means of the karyopyknotic index (KPI), while the degree of maturation of the vaginal epithelium was estimated visually. Urinary bacteria were cultivated. A pronounced and progressive rise in KPI was seen in both the vaginal and the urethral epithelium following daily E3 treatment. However, neither of the two maintenance dosages was sufficient to sustain the initial maturation of the vaginal and urethral epithelium induced by E3, since the KPI returned to pretreatment values within 4 weeks. The effect of E3 administration on the vaginal epithelium was overestimated by the visual assessment method. No changes were seen in urinary bacteria. Medroxyprogesterone acetate was given before and after E3 treatment. None of the women suffered from withdrawal bleeding.

Pharmacokinetics and pharmacodynamic effects of vaginal oestradiol administration from silastic rings in post-menopausal women.

Silastic rings releasing approximately 200 microgram of 17beta-oestradiol per day were inserted into the vaginas of 4 post-menopausal women for one to three 21-day periods. Plasma concentrations of oestrone and oestradiol were analysed by radioimmunoassay. The effect of circulating oestrogens on FSH, LH and sex-hormone binding globulin (SHBG) levels as the well as on the endometrium was studied. During the first 24 h of treatment the plasma oestradiol levels were higher than the oestrone levels. But during the following days of the 21-day periods, the levels of the two oestrogens were almost equal, varying between about 100 and 200 pg/ml plasma, a pattern similar to that seen in fertile women. the release of oestradiol from the ring gave stable plasma oestrogen levels. The FSH and LH levels were clearly depressed while the SHBG levels did not change. Characteristics of oestrogen influence were found in endometrial biopsies. The rings were well accepted and could be inserted and removed easily by the women. Absorption of oestradiol from the vagina is good and more complete than after oral administration allowing lower doses to be used for treatment.

Endometrial effects of levonorgestrel and estradiol: A Scanning electron microscopic study of the luminal epithelium.

Fertile women in the follicular phase possessed an uterine luminal surface with many ciliated cells and with non-ciliated cells, which carried numerous, fairly long microvilli. A moderate number of the non-ciliated cells had an irregular surface with small apical protrusions. Postmenopausal women had an endometrial surface containing rather flat cells. Ciliated cells were seldon encountered, and the non-ciliated cells possessed mostly only few short microvilli. When menopausal women had been wearing estradiol-containing intravaginal rings for three weeks, the uterine surface had developed many ciliated cells, and the non-ciliated cells now possessed many long microvilli. This appearance resembles that appearing during the follicular phase. Fertile women with levonorgestrel-containing subdermal implants or intravaginal rings showed a surface epithelium with few ciliated cells and with non-ciliated cells possessing short and irregular microvilli; that is, an epithelium less developed than that from a cyclic women. Adding estradiol to the levonorgestrel-containing intravaginal rings resulted in an estrogen response with an increase in number and length of the microvilli and an appearance of a few small apical protrusions.

PIP: This scanning electron microscopic study (SEM) investigated the extent of estrogenic influences on endometrium; biopsy specimens from 2 groups of women were compared, one group using a levonorgestrel-only containing vaginal ring and the other using a levonorgestrel-estradiol containing vaginal ring; these women were all fertile. To evaluate the effect of estradiol, biopsies were also taken from menopausal women using vaginal rings containing estradiol alone. These were all compared with control biopsies from normal fertile women from follicular phase-menopause. Fertile women in follicular phase possessed a uterine luminal surface with many ciliated cells and those nonciliated cells carried numerous, fairly long microvilli. Some nonciliated cells had irregular surfaces with small apical protrusions. Postmenopausal women's endometrial surfaces showed flat cells; ciliated cells were seldom seen, and nonciliated cells had mostly short, and very few, microvilli. Menopausal women, who had worn the estradiol ring for 3 weeks, showed ciliated uterine surfaces, and the remaining nonciliated cells now possessed long microvilli, similar to follicular-phase endometrium. Fertile women with levonorgestrel-only implants or rings showed surface epithelium with few ciliated cells and with nonciliated cells of short and irregular microvilli. Adding estradiol to the levenorgestrel ring gave an estrogen response with increased number and length of microvilli and the appearance of a few small apical protrusions.

Enterohepatic recirculation of oestriol studied in cholecystectomized and non-cholecystectomized menopausal women.

This study was done to evaluate the absorption of a single oral dose of 12 mg oestriol (Triovex, Leo AB, Sweden) and to confirm the hypothesis that the enterohepatic recirculation can prolong the plasma oestriol elevation obtained. Twelve menopausal women, six of whom had been cholecystectomized earlier, were given 12 mg oestriol orally. Fatty meals were given immediately after drug administration and then at four hourly intervals. Fat was given to induce the bileflow and provide oestriol to the intestine for deconjugation and enterohepatic recycling. One of the non-cholecystectomized women also remained fasting for 24 hours after oestriol administration. Plasma concentrations of unconjugated oestriol were measured by a specific RIA-method. In all women the plasma oestriol levels were considerably elevated for 24 hours. In the non-cholecystectomized women the plasma oestriol levels fluctuated in relation to meals whereas in the cholecystectomized women the fluctuations were not as pronounced, indicating that the release of biliary oestriol metabolites is the source of intestinal degradation and reabsorption to the systemic circulation. Fasting also gave increased and stable plasma oestriol levels. After a high oral dosage of oestriol, the enterohepatic recycling renders oestriol an enhanced potency since the plasma oestriol elevation time is prolonged.

Oral versus vaginal absorption in oestradiol in postmenopausal women. Effects of different particles sizes.

Crystalline oestradiol-17 beta is poorly absorbed from the gastrointestinal tract. Three different fractions and a standard fraction containing oestradiol- 17 beta of a known particle size and surface area, were administered orally, to postmenopausal women, to test if changes in particle size will influence the absorption. The bioavailability of each fraction was determined by measurements of peripheral plasma oestrogens. Two different dosages of the standard fraction were given vaginally to compare the bioavailability after oral and vaginal administration. The gastrointestinal absorption was dependent of the particle size of oestradiol. The smaller particle the more rapid and effective absorption as reflected by increasing area under the plasma concentration curve of oestrone and oestradiol. The smallest particle, however, resulted in a pronounced initial oestradiol peak. The coarser particles were more slowly absorbed with more even plasma oestrogen elevation for a sustained period of time. The vaginal absorption of oestradiol was more effective than the gastrointestinal. When the same amount of an equal preparation according to particle size, was given vaginally the maximal plasma concentration was almost 40 times higher than when given orally.

Estriol: absorption after long-term vaginal treatment and gastrointestinal absorption as influenced by a meal.

This study was designed to evaluate the vaginal absorption of estriol when given as a 21-day treatment. Vaginal absorption was compared with the oral absorption of a known estriol preparation (TriovexR, Leo AB, Sweden). One mg of estriol was administered intravaginally once a day for 21 days to 6 menopausal women. Plasma concentrations of unconjugated estriol were measured by a specific RIA-method at frequent intervals during 24 hours on the first and 21st day of treatment. One month later, 10 mg of estriol was given once orally and plasma estriol concentrations were measured in the same way. At vaginal administration, the absorption of estriol was very effective. When measured on the 21st day, the absorption had declined significantly but was still nearly in the same range as after oral administration of 10 mg of estriol. At oral administration, there was an initial plasma estriol elevation for 3 hours only followed by a second one immediately postprandially. It is concluded that estriol is readily absorbed from the vagina, but the absorption does decline significantly during prolonged treatment. A large single oral dose of estriol provides initially a high plasma estriol concentration but also a second one induced by eating a meal, possibly indicating an enterohepatic recirculation of estriol.

Enterohepatic recirculation of oestriol: inhibition by activated charcoal.

We have earlier reported on a prolonged effect of orally administered oestriol caused by its enterohepatic recycling after reabsorption from the intestine. The aim of the present study was to test if oral administration of activated charcoal could inhibit the enterohepatic recirculation of orally given oestriol. Plasma concentrations of unconjugated oestriol were measured using a specific radioimmunoassay (RIA). Twelve mg oestriol administered orally to postmenopausal women resulted in elevated plasma oestriol levels for more than 24 h. Plasma oestriol fluctuations in relation to meals were seen. When activated charcoal was given 3 h after oestriol administration, the plasma oestriol concentration declined without further fluctuations and returned to the pretreatment value within 6 h. Our data indicate that oestriol given orally undergoes enterohepatic recirculation after reabsorption from the intestine since administration of charcoal, which binds steroids, resulted in a rapidly declining oestriol level. It is concluded that the prolonged oestriol elevation, which is normally seen, is caused by enterohepatic recycling.

Endometrial effect of oral estriol treatment in postmenopausal women.

Estriol is a weak estrogen with a claimed specific action on the epithelium in cervix uteri and vagina and with no or limited ability to induce endometrial proliferation. In a previous pharmacokinetic study we have shown elevated estriol levels for only 2-3 hours after oral administration of the drug. The present study was performed to test if estriol, when given orally in daily divided doses to postmenopausal women, has any effect on the endometrium. Twenty postmenopausal women who had no vaginal bleeding in response to lynestrenol (Orgametil 5 mgX2XV) were treated with 6 mg estriol a day (Ovesterin 2 mgX3), divided into three doses, for 2 up to 3.5 months. When lynestrenol (5 mgX2XV) was given following the estriol treatment periods, 12 women out of 20 experienced a vaginal bleeding and one reported spotting. Endometrial biopsies in ten of these women who had a bleeding were examined histologically. The endometrium was atrophic in four women, proliferative in two, slightly hyperplastic in one and showed signs of weak hormonal activity in one. Two women had secretory endometrium. It is concluded that estriol, administered in a way that gives prolonged elevation of the blood levels, is able to produce the same effect on the endometrium as other estrogens.

PIP: Estriol is a weak estrogen with a claimed specific action on the epithelium in cervix uteri and vagina and with limited or no ability to induce endometrial proliferation. In a previous pharmacokinetic study, we have shown elevated estriol levels for only 2-3 hours following oral administration of the drug. The present study was performed to determine if estriol, when given orally in daily divided doses to postmenopausal women, has any effect on the endometrium. 20 postmenopausal women with no vaginal bleeding in response to lynestrenol (Orgametil (R) 5 mgx2xV) were treated with 6 mg estriol/day (Ovesterin (R) 2 mgx3), divided into 3 doses, for between 2 and 3.5 months. When lynestrenol (5 mgx2xV) was given following the estriol treatment periods, 2 of 20 women experienced vaginal bleeding and 1 reported spotting. Endometrial biopsies in 10 of those women who had bleeding were examined histologically. The endometrium was atrophic in 4 women, proliferative in 2, slightly hyperplastic in 1, and showed signs of weak hormonal activity in 1. 2 women had secretory endometrium. It is concluded that estriol, administered in a way which prolongs elevation of the blood levels, is able to produce the same effect on the endometrium as other estrogens.