Field-resolved high-order sub-cycle nonlinearities in a terahertz semiconductor laser.

The exploitation of ultrafast electron dynamics in quantum cascade lasers (QCLs) holds enormous potential for intense, compact mode-locked terahertz (THz) sources, squeezed THz light, frequency mixers, and comb-based metrology systems. Yet the important sub-cycle dynamics have been notoriously difficult to access in operational THz QCLs. Here, we employ high-field THz pulses to perform the first ultrafast two-dimensional spectroscopy of a free-running THz QCL. Strong incoherent and coherent nonlinearities up to eight-wave mixing are detected below and above the laser threshold. These data not only reveal extremely short gain recovery times of 2 ps at the laser threshold, they also reflect the nonlinear polarization dynamics of the QCL laser transition for the first time, where we quantify the corresponding dephasing times between 0.9 and 1.5 ps with increasing bias currents. A density-matrix approach reproducing the emergence of all nonlinearities and their ultrafast evolution, simultaneously, allows us to map the coherently induced trajectory of the Bloch vector. The observed high-order multi-wave mixing nonlinearities benefit from resonant enhancement in the absence of absorption losses and bear potential for a number of future applications, ranging from efficient intracavity frequency conversion, mode proliferation to passive mode locking.

Cannabis use while trying to conceive: a prospective cohort study evaluating associations with fecundability, live birth and pregnancy loss.

STUDY QUESTION: Is cannabis use assessed via urinary metabolites and self-report during preconception associated with fecundability, live birth and pregnancy loss? SUMMARY ANSWER: Preconception cannabis use was associated with reduced fecundability among women with a history of pregnancy loss attempting pregnancy despite an increased frequency of intercourse. WHAT IS KNOWN ALREADY: Cannabis use continues to rise despite limited evidence of safety during critical windows of pregnancy establishment. While existing studies suggest that self-reported cannabis use is not associated with fecundability, self-report may not be reliable. STUDY DESIGN, SIZE, DURATION: A prospective cohort study was carried out including 1228 women followed for up to six cycles while attempting pregnancy (2006 to 2012), and throughout pregnancy if they conceived. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 18-40 years with a history of pregnancy loss (n = 1228) were recruited from four clinical centers. Women self-reported preconception cannabis use at baseline and urinary tetrahydrocannabinol metabolites were measured throughout preconception and early pregnancy (up to four times during the study: at baseline, after 6 months of follow-up or at the beginning of the conception cycle, and weeks 4 and 8 of pregnancy). Time to hCG-detected pregnancy, and incidence of live birth and pregnancy loss were prospectively assessed. Fecundability odds ratios (FOR) and 95% CI were estimated using discrete time Cox proportional hazards models, and risk ratios (RRs) and 95% CI using log-binomial regression adjusting for age, race, BMI, education level, baseline urine cotinine, alcohol use and antidepressant use. MAIN RESULTS AND THE ROLE OF CHANCE: Preconception cannabis use was 5% (62/1228), based on combined urinary metabolite measurements and self-report, and 1.3% (11/789) used cannabis during the first 8 weeks of gestation based on urinary metabolites only. Women with preconception cannabis use had reduced fecundability (FOR 0.59; 95% CI 0.38, 0.92). Preconception cannabis use was also associated with increased frequency of intercourse per cycle (9.4 ± 7 versus 7.5 ± 7 days; P = 0.02) and higher LH (percentage change 64%, 95% CI 3, 161) and higher LH:FSH ratio (percentage change 39%, 95% CI 7, 81). There were also suggestive, though imprecise, associations with anovulation (RR 1.92, 95% CI 0.88, 4.18), and live birth (42% (19/45) cannabis users versus 55% (578/1043) nonusers; RR 0.80, 95% CI 0.57, 1.12). No associations were observed between preconception cannabis use and pregnancy loss (RR 0.81, 95% CI 0.46, 1.42). Similar results were observed after additional adjustment for parity, income, employment status and stress. We were unable to estimate associations between cannabis use during early pregnancy and pregnancy loss due to limited sample size. LIMITATIONS, REASONS FOR CAUTION: Owing to the relatively few cannabis users in our study, we had limited ability to make conclusions regarding live birth and pregnancy loss, and were unable to account for male partner use. While results were similar after excluding smokers, alcohol use and any drug use in the past year, some residual confounding may persist due to these potential co-exposures. WIDER IMPLICATIONS OF THE FINDINGS: These findings highlight potential risks on fecundability among women attempting pregnancy with a history of pregnancy loss and the need for expanded evidence regarding the reproductive health effects of cannabis use in the current climate of increasing legalization. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contract numbers: HHSN267200603423, HHSN267200603424, HHSN267200603426, HHSN275201300023I). Jeannie G. Radoc has been funded by the National Institutes of Health Medical Research Scholars Program, a public-private partnership supported jointly by the National Institutes of Health and generous contributions to the Foundation for the National Institutes of Health from the Doris Duke Charitable Foundation (DDCF Grant # 2014194), Genentech, Elsevier, and other private donors. The authors report no conflict of interest in this work and have nothing to disclose. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT00467363.

Terahertz photonic integrated circuit for frequency tuning and power modulation.

The quantum cascade laser is a powerful solid-state source of terahertz-frequency radiation. However, integrating multiple photonic functions into a monolithic platform in this frequency range is non-trivial due to the scaling of photonic structures for the long terahertz wavelengths and the low frequency tuning coefficients of the quantum cascade lasers. Here, we have designed a simple terahertz-frequency photonic integrated circuit by coupling a racetrack resonator with a ridge laser in the longitudinal direction to design a notch filter. The transmission properties of this filter structure are dependent on the phase matching and losses in the coupled racetrack and results in a comb of stopband frequencies. We have optimized the comb separation by carefully selecting the cavity dimensions of the racetrack resonator to suppress longitudinal modes in the ridge laser enabling single-mode emission. The emission frequencies and output power from laser are controlled through appropriate control of drive currents to the ridge and the racetrack resonator. The emission frequency is electrically tuned over ∼81 GHz exploiting Stark shift of the gain as a function of drive current at the ridge laser, coinciding with an output power variation of ∼27% of the peak power (at a heat sink temperature of 50 K). The output power from the ridge also varied by ∼30% and the frequency was tuned by a further 10 GHz when the driving conditions at the ridge laser are invariant and the current at the racetrack resonator was varied. To our best knowledge, this is the first report of a frequency engineering, tuning and power modulation of terahertz-frequency quantum cascade lasers using a photonic integrated circuit.

Increasing the sensitivity of terahertz split ring resonator metamaterials for dielectric sensing by localized substrate etching.

We demonstrate a significant enhancement in the sensitivity of split ring resonator terahertz metamaterial dielectric sensors by the introduction of etched trenches into their inductive-capacitive gap area, both through finite element simulations and in experiments performed using terahertz time-domain spectroscopy. The enhanced sensitivity is demonstrated by observation of an increased frequency shift in response to overlaid dielectric material of thicknesses up to 18 µm deposited on to the sensor surface. We show that sensitivity to the dielectric is enhanced by a factor of up to ∼2.7 times by the incorporation of locally etched trenches with a depth of ∼3.4 µm, for example, and discuss the effect of the etching on the electrical properties of the sensors. Our experimental findings are in good agreement with simulations of the sensors obtained using finite element methods.

Silver-based surface plasmon waveguide for terahertz quantum cascade lasers.

Terahertz-frequency quantum cascade lasers (THz QCLs) based on ridge waveguides incorporating silver waveguide layers have been investigated theoretically and experimentally, and compared with traditional gold-based devices. The threshold gain associated with silver-, gold- and copper-based devices, and the effects of titanium adhesion layers and top contact layers, in both surface-plasmon and double-metal waveguide geometries, have been analysed. Our simulations show that silver-based waveguides yield lower losses for THz QCLs across all practical operating temperatures and frequencies. Experimentally, QCLs with silver-based surface-plasmon waveguides were found to exhibit higher operating temperatures and higher output powers compared to those with identical but gold-based waveguides. Specifically, for a three-well resonant phonon active region with a scaled oscillator strength of 0.43 and doping density of 6.83 × 1015 cm-3, an increase of 5 K in the maximum operating temperature and 40% increase in the output power were demonstrated. These effects were found to be dependent on the active region design, and greater improvements were observed for QCLs with a larger radiative diagonality. Our results indicate that silver-based waveguide structures could potentially enable THz QCLs to operate at high temperatures.

Extraction-controlled terahertz frequency quantum cascade lasers with a diagonal LO-phonon extraction and injection stage.

We report an extraction-controlled terahertz (THz)-frequency quantum cascade laser design in which a diagonal LO-phonon scattering process is used to achieve efficient current injection into the upper laser level of each period and simultaneously extract electrons from the adjacent period. The effects of the diagonality of the radiative transition are investigated, and a design with a scaled oscillator strength of 0.45 is shown experimentally to provide the highest temperature performance. A 3.3 THz device processed into a double-metal waveguide configuration operated up to 123 K in pulsed mode, with a threshold current density of 1.3 kA/cm2 at 10 K. The QCL structures are modeled using an extended density matrix approach, and the large threshold current is attributed to parasitic current paths associated with the upper laser levels. The simplicity of this design makes it an ideal platform to investigate the scattering injection process.

Mode-locking of a terahertz laser by direct phase synchronization.

A novel scheme to achieve mode-locking of a multimode laser is demonstrated. Traditional methods to produce ultrashort laser pulses are based on modulating the cavity gain or losses at the cavity roundtrip frequency, favoring the pulsed emission. Here, we rather directly act on the phases of the modes, resulting in constructive interference for the appropriated phase relationship. This was performed on a terahertz quantum cascade laser by multimode injection seeding with an external terahertz pulse, resulting in phase mode-locked terahertz laser pulses of 9 ps duration, characterized unambiguously in the time domain.

Management of sports-related concussions.

Mild head injury is a frequent occurrence in a multitude of athletic endeavors across all levels of play. Clinicians should carefully consider all interventions at their disposal to reduce the prevalence and severity of injury to protect those involved. The exploration and evaluation of using properly fitted mouthguards to provide effective, albeit limited, defense against brain injury merits attention. The minimal costs of such an intervention when properly applied would no doubt reap numerous benefits in terms of reducing the medical, financial, cognitive, psychological, and social consequences of mild head injury. The cosmetic salvation would be no small side effect to efficacious, properly fitted mouthguard use.

Acute skier's thumb repaired with a proximal phalanx suture anchor.

The purpose of this study was to determine the functional outcome of a surgical technique for the repair of injuries of the ulnar collateral ligament of the thumb. A 14-point questionnaire was developed to determine functional outcome after surgical repair of acute ulnar collateral ligament rupture. Early ulnar collateral ligament repair was performed on 58 patients with grade III sprains (complete rupture) of the ligament using a new technique that employs a suture anchor for fixation. Forty-five patients were interviewed at a minimum postoperative interval of 12 months and were included in this study. Forty-four patients (98%) believed they had a stable repair, were satisfied with their surgery, and would have it again if necessary. Forty-four patients (98%) were not hindered in their day-to-day activities and had a functional range of motion. Mild discomfort was felt by eight of our patients (17%), but only three patients (7%) had pain with activities. The average time to return to skiing was 1.7 days. The use of a suture anchor provided a strong and stable repair if the surgery was performed early.

Primary traumatic anterior shoulder dislocation in patients 40 years of age and older.

During three consecutive ski seasons (1991 to 1994), 125 patients 40 years of age and older without previous shoulder injuries or surgery sustained a traumatic first-time anterior shoulder dislocation. At a minimum of 2 years' follow-up, patients were contacted to determine long-term outcome and to identify factors leading to prolonged morbidity or the need for surgical intervention. Fifty-two patients were available for interview. A modified Rowe shoulder score showed 32 excellent, nine good, eight fair, and three poor results. Eighteen (35%) rotator cuff tears were subsequently identified, with only 11 (61%) of these patients obtaining an excellent or good outcome (P = .011). Of the 11 patients with a fair or poor result, seven (64%) had a rotator cuff tear. Of the 12 patients with isolated cuff tears, 84% had an excellent or good result when treated surgically, compared with 50% when treated nonsurgically. Our findings indicate that recurrence is not a frequent complication of traumatic anterior shoulder dislocation in this age-group (4%). However, prolonged morbidity secondary to rotator cuff tear is more prevalent than in a younger population. We believe early diagnosis of rotator cuff pathology by either magnetic resonance imaging (MRI) or arthrogram with subsequent surgical repair can lead to faster restoration of function and a better outcome in these select individuals.

The impact of surgical timing on postoperative motion and stability following anterior cruciate ligament reconstruction.

A prospective study was designed to determine the impact of surgical timing on postoperative motion and stability following anterior cruciate ligament (ACL) reconstructive surgery. The study population was limited to acute ACL ruptures from downhill skiing undergoing arthroscopic ACL surgery without arthrotomy or surgical intervention for other ligamentous structures; 185 patients were entered into four separate groups based on the time interval from injury to surgery. Motion and stability were tested at multiple time points from the index surgery and adverse events were recorded. We found no statistical difference in restoration of extension or flexion in any group at any time point. KT-1000 data at 12 months showed a side-to-side difference of < or = 3 mm in 94%, with 6% showing a side-to-side difference of > 3 and < or = 5 mm. We conclude that, in this population, by using modern arthroscopic surgical techniques and an aggressive postoperative physical therapy protocol, motion and stability can be restored in a high percentage of patients and that surgical success is independent of the timing of surgery.

A strategy for improving the supervision and performance of moonlighting residents.

BACKGROUND: In 1990 the Ambulatory Care Service of the Ralph H. Johnson Department of Veterans Affairs Medical Center, affiliated with the Medical University of South Carolina College of Medicine, developed written clinical protocols for the management of patients with certain high-risk medical conditions. METHOD: Appropriateness of care was assessed by determining physician compliance to the protocols over a 24-month period (October 1990-September 1992). All physicians who did not comply received individualized feedback from the service chief. For the first 12 months, both staff physicians and moonlighting second- and third-year medical residents were assessed (a total of seven staff physicians and 20 residents participated in the study). For the second 12 months, only the residents were assessed. RESULTS: The moonlighting residents were notably less consistent than the staff physicians in protocol compliance (95-100% for the staff physicians; 78-100% for the moonlighters). Additional interventions were then implemented to improve the moonlighters' utilization of the protocols. Moonlighters' compliance over the subsequent 12 months was less variable (mean compliance of 92%, SD, 3%, the first year versus 95%, SD, 8%, the second year). CONCLUSION: The strategy seemed to improve the supervision and performance of the moonlighting residents and promoted consistent delivery of high-quality outpatient care.

Grade III avulsion fracture repair on the UCL of the proximal joint of the thumb.

A technique is presented for repair of grade III avulsion fractures of the ulnar collateral ligament when the bony avulsion fragment in the thumb is too small or too comminuted to allow simple repair. The case presented demonstrates that a single suture-to-bone anchor can provide secure ligament fixation without the need for external pull-out wires or buttons and can make possible an early return to activity.

Treatment of comminuted distal radial fractures with preliminary horizontal finger trap traction and a Roger-Anderson external fixation device.

Over a five-year period, 43 patients with comminuted distal radial fractures were treated with a Roger-Anderson external fixation device after the fracture was aligned in Strong's horizontal finger trap traction. Nineteen patients (21 wrists) were available for personal interview and radiographic follow-up. A 0.5-mm loss of radial height and an average loss of 2.4 degrees of palmar angulation presented. Range of motion (ROM) was excellent, stiffness was nonexistent or minimal in 81%, pain was nonexistent or minimal in 86%, and weakness of grasp was nonexistent or minimal in 81%. Complications were minimal; they included three pin tract infections, two of which required pin removal before they resolved. One patient fractured a pin that also required removal. Strong's horizontal finger trap traction and the Roger-Anderson external fixation device simplified the sometimes difficult treatment of this fracture. It seems to be most effective in young athletic individuals who have good bone stock and very comminuted fractures.

Effects of intermittent feeding upon body weight and lifespan in inbred mice: interaction of genotype and age.

Beginning at either 1.5, 6 or 10 months of age, male mice from the A/J and C57BL/6J strains and their F1 hybrid, B6AF1/J were fed a diet (4.2 kcal/g) either ad libitum every day or in a restricted fashion by ad libitum feeding every other day. Relative to estimates for ad libitum controls, the body weights of the intermittently-fed restricted C57BL/6J and hybrid mice were reduced and mean and maximum life span were incremented when the every-other-day regimen was initiated at 1.5 or 6 months of age. When every-other-day feeding was introduced at 10 months of age, again both these genotypes lost body weight relative to controls; however, mean life span was not significantly affected although maximum life span was increased. Among A/J mice, intermittent feeding did not reduce body weight relative to ad libitum controls when introduced at 1.5 or 10 months of age; however, this treatment did increase mean and maximum life span when begun at 1.5 months, while it decreased mean and maximum life span when begun at 10 months. When restricted feeding was introduced to this genotype at 6 months of age, body weight reduction compared to control values was apparent at some ages, but the treatment had no significant effects on mean or maximum life span. These results illustrate that the effects of particular regimens of dietary restriction on body weight and life span are greatly dependent upon the genotype and age of initiation. Moreover, when examining the relationship of body weight to life span both between and within the various groups, it was clear that the complexity of this relationship made it difficult to predict that lower body weight would induce life span increment.

Changing patterns in tibial fractures resulting from skiing.

Of the 734 adult tibial fractures treated in Aspen, Colorado, from 1968-1978, follow-up results were obtained on 527 (72%). The fractures were analyzed with regard to rate of healing, age of patient, and location of fractures. There was a statistically significant increase in healing time with increasing age between ages 16-40. The location of tibial fracture (proximal, middle, distal) had no significant influence on rate of healing. The occurrence of open tibial fracture was low (3% of total) and in most instances wounds were benign (Class I). Compartment syndrome is rarely encountered in skiing fracture because of the relatively low energy involved. All tibial fractures occurring between 1982-1984 were reviewed and compared to the earlier series. This comparison confirmed the continual overall decline in rate of tibial fracture from skiing (from 12.9/100,000 skier days in 1968 to 2.9/100,000 skier days in 1983). This decline was primarily in spiral fractures (from 70% of total in 1968 to 50% in 1983). The percent of transverse fractures was unchanged (+/- 15%) while the percent of short oblique fractures increased from 11% to 33%. Properly adjusted and maintained safety equipment afforded reasonable protection from spiral fractures of the tibia, but a conceptual departure from the current release binding design would be required to protect against the benign moments that produced transverse and short oblique fracture. The current treatment philosophy is based on fracture type and the availability or experience with newer treatment modes.

Acute surgical repair of the skier's thumb.

Complete ulnar collateral ligament tears incurred during the period fall 1977 through spring 1979 were treated under regional anesthesia by a single group of surgeons in an identical fashion as outpatients. Of 123 thumbs repaired, 69 (59%) were available for follow-up examination. There were 34 women and 35 men with an average age of 34.5 years (range, 16-61 years). The follow-up period averaged 31.6 months (range, 16-46 months). Weakness of pinch was described as none or mild in 66 (96%) and significant in only three (4%). Stiffness was described as none or mild in 66 (96%), moderate in two (3%), and severe in one (1%). Pain was described as none or mild in 68 (99%) and moderate in one (1%). Sixty-two patients (90%) preferred outpatient surgery with regional anesthesia whereas only seven (10%) did not. Forty-five (65%) of the 69 patients who required surgery had used traditional poles with straps, suggesting the pole as the causative factor. However, only 20% of noninjured skiers during the 1981-1982 season were using traditional poles with straps, and the total number of complete ulnar collateral ligament repairs did not decrease with the same number of skiers. Therefore, the change in pole design has not decreased the incidence of total ulnar collateral ligament tears. The results of acute surgical repair as an outpatient with regional anesthesia are excellent; 96% of the patients were pleased with the results. If the lesion is overlooked, the results of secondary construction are not nearly as good.

Dietary restriction benefits learning and motor performance of aged mice.

Female C3B10RF1 mice maintained on either a control (approximately 95 kcal/week) or restricted (approximately 55 kcal/week) diet since weaning were tested in a behavioral battery at 11 to 15 or 31 to 35 months of age (middle-aged vs. aged). Age-related declines observed among control groups in tests of motor coordination (rotorod) and learning (complex maze) were prevented by the restriction regime. In addition, diet restriction increased locomotor activity in a runwheel cage among mice of both ages but did not affect exploratory activity in a novel arena.

Primary knee ligament repair--revisited.

There were 4710 knee sprains resulting from skiing in the four Aspen ski areas between 1976 and 1979. Twenty percent of the patients (942) had complete tears. Of these, 302 elected to remain in Aspen for treatment. All were treated by primary ligament repair without augmentation. These cases were evaluated an average of 42 months after injury. Patients with isolated tears of the medial collateral ligament were found to be doing well; virtually all of them had returned to preinjury activity levels. Thirty-six percent of the isolated anterior cruciate repairs were rated failures, and 43% of the combination ACL-MCL injuries had failed because of anterior cruciate deficiency. Twenty-nine percent of the ACL and ACL-MCL injuries had meniscal tears. Cases that included meniscectomy had a failure rate twice as great as those in which the meniscus was preserved. The results following repair of anterior cruciate tears were not acceptable, and augmentation was indicated. Primary repair of medial collateral ligament tears produced excellent results. Meniscal tears were frequent in association with ligament disruption. Ligament repairs were less satisfactory when meniscectomy was performed at the time of the repair.

Effects of intermittent feeding upon growth, activity, and lifespan in rats allowed voluntary exercise.

From weaning until death, male Wistar rats were housed in activity-wheel cages with one group maintained on an ad libitum (AL) diet and another provided the diet every-other-day (EOD). EOD-fed rats had a mean lifespan of 124 weeks compared to 103 weeks for AL-fed rats. While post-weaning body weight and growth rates were reduced among the EOD-fed animals compared to AL-fed animals, there was no significant difference in growth duration. Positive correlations were observed between lifespan and estimates of growth rate and duration in the AL group but not in the EOD group; thus, little evidence was produced to support the hypothesis that growth rate is inversely related to longevity. While the EOD feeding regimen resulted in higher activity levels later in life, wheel activity levels were actually lower in this group in early life compared to the AL group. The observation of reduced wheel activity among young rats fed EOD was replicated in a second experiment. Thus, little support was obtained for the hypothesis that increased activity mediates the beneficial effects of dietary restriction on longevity, unless this mechanism is active late in the lifespan.