Plan U: Universal access to scientific and medical research via funder preprint mandates.

Preprint servers such as arXiv and bioRxiv represent a highly successful and relatively low cost mechanism for providing free access to research findings. By decoupling the dissemination of manuscripts from the much slower process of evaluation and certification by journals, preprints also significantly accelerate the pace of research itself by allowing other researchers to begin building on new results immediately. If all funding agencies were to mandate posting of preprints by grantees-an approach we term Plan U (for "universal")-free access to the world's scientific output for everyone would be achieved with minimal effort. Moreover, the existence of all articles as preprints would create a fertile environment for experimentation with new peer review and research evaluation initiatives, which would benefit from a reduced barrier to entry because hosting and archiving costs were already covered.

Careers in Science Publishing.

Publishing, particularly journal publishing, offers the chance to stay in contact with science and scientists and so appeals to people considering leaving the laboratory for another career. Professional editors of research journals review and select manuscripts for publication, negotiating as needed with authors and referees. Review journal editors commission articles on suitable topics and work with authors to shape manuscripts appropriately for the readership. Experienced individuals may advance to become a Managing Editor and further to a Publisher/Publishing Director position within a company or a not-for-profit organization, with responsibility for the business aspects of a publishing program. Would-be editors must be prepared to broaden their scientific knowledge, engage in person with community members, be tactful but firm in decision making, and work happily in the background. Evidence of a genuine interest in the communication of science beyond the usual writing and publishing of papers is necessary to compete successfully for entry positions.

Tips and tricks of ureteroscopy: consensus statement. Part II. Advanced ureteroscopy.

Our "tips and tricks" focuses on all aspects of upper tract endourology and we hope these will be of use to all trainees and consultants who perform ureteroscopy. We report an "expert consensus view" from experienced endourological surgeons, on all aspects of advanced ureteroscopic techniques, with a particular focus on avoiding and getting out of trouble while performing ureteroscopy. In this paper we provide a summary of placing ureteric access sheath, flexible ureteroscopy, intra renal stone fragmentation and retrieval, maintaining visual clarity and biopsy of ureteric and pelvicalyceal tumours.

Vestibular contribution to balance control in the medial gastrocnemius and soleus.

The soleus (Sol) and medial gastrocnemius (mGas) muscles have different patterns of activity during standing balance and may have distinct functional roles. Using surface electromyography we previously observed larger responses to galvanic vestibular stimulation (GVS) in the mGas compared with the Sol muscle. However, it is unclear whether this difference is an artifact that reflects limitations associated with surface electromyography recordings or whether a compensatory balance response to a vestibular error signal activates the mGas to a greater extent than the Sol. In the present study, we compared the effect of GVS on the discharge behavior of 9 Sol and 21 mGas motor units from freely standing subjects. In both Sol and mGas motor units, vestibular stimulation induced biphasic responses in measures of discharge timing [11 ± 5.0 (mGas) and 5.6 ± 3.8 (Sol) counts relative to the sham (mean ± SD)], and frequency [0.86 ± 0.6 Hz (mGas), 0.34 ± 0.2 Hz (Sol) change relative to the sham]. Peak-to-trough response amplitudes were significantly larger in the mGas (62% in the probability-based measure and 160% in the frequency-based measure) compared with the Sol (multiple P < 0.05). Our results provide direct evidence that vestibular signals have a larger influence on the discharge activity of motor units in the mGas compared with the Sol. More tentatively, these results indicate the mGas plays a greater role in vestibular-driven balance corrections during standing balance.

Acromegaly Presenting as Erectile Dysfunction: Case Reports and Review of the Literature.

Erectile dysfunction (ED) is a common yet complex condition. The authors report two cases of acromegaly presenting with ED and hypogonadotropic hypogonadism. Surgical cure of the acromegaly was associated with either an improvement or resolution of hypogonadotropic hypogonadism-associated ED. Active acromegaly should be considered in the differential diagnosis of ED presenting with supporting clinical features, particularly hypogonadotropic hypogonadism.

Tips and tricks of ureteroscopy: consensus statement Part I. Basic ureteroscopy.

Ureteroscopy is fast becoming the first line treatment option for the majority of urinary tract stones. Ureteroscopy training can be performed in a variety of ways including simulation, hands on ureteroscopy courses and supervised operative experience. We report an "expert consensus view" from experienced endourological surgeons, on all aspects of basic ureteroscopic techniques, with a particular focus on avoiding and getting out of trouble while performing ureteroscopy. In this paper we provide a summary of treatment planning, positioning, cannulation of ureteric orifice, guidewire placement, rigid ureteroscopy and stone fragmentation.

Absence of lateral gastrocnemius activity and differential motor unit behavior in soleus and medial gastrocnemius during standing balance.

In a standing position, the vertical projection of the center of mass passes in front of the ankle, which requires active plantar-flexor torque from the triceps surae to maintain balance. We recorded motor unit (MU) activity in the medial (MG) and lateral (LG) gastrocnemius muscle and the soleus (SOL) in standing balance and voluntary isometric contractions to understand the effect of functional requirements and descending drive from different neural sources on motoneuron behavior. Single MU activity was recorded in seven subjects with wire electrodes in the triceps surae. Two 3-min standing balance trials and several ramp-and-hold contractions were performed. Lateral gastrocnemius MU activity was rarely observed in standing. The lowest thresholds for LG MUs in ramp contractions were 20-35 times higher than SOL and MG MUs (P < 0.001). Compared with MUs from the SOL, MG MUs were intermittently active (P < 0.001), had higher recruitment thresholds (P = 0.022), and greater firing rate variability (P < 0.001); this difference in firing rate variability was present in standing balance and isometric contractions. In SOL and MG MUs, both recruitment of new MUs (R(2) = 0.59-0.79, P < 0.01) and MU firing rates (R(2) = 0.05-0.40, P < 0.05) were associated with anterior-posterior and medio-lateral torque in standing. Our results suggest that the two heads of the gastrocnemius may operate in different ankle ranges with the larger MG being of primary importance when standing, likely due to its fascicle orientation. These differences in MU discharge behavior were independent of the type of descending neural drive, which points to a muscle-specific optimization of triceps surae motoneurons.

Muscle-specific modulation of vestibular reflexes with increased locomotor velocity and cadence.

Vestibular information is one of the many sensory signals used to stabilize the body during locomotion. When locomotor velocity increases, the influence of these signals appears to wane. It is unclear whether vestibular signals are globally attenuated with velocity or are influenced by factors such as whether a muscle is contributing to balance control. Here we investigate how vestibular sensory signals influence muscles of the leg during locomotion and what causes their attenuation with increasing locomotor velocity. We hypothesized that 1) vestibular signals influence the activity of all muscles engaged in the maintenance of medio-lateral stability during locomotion and 2) increases in both cadence and velocity would be associated with attenuation of these signals. We used a stochastic vestibular stimulus and recorded electromyographic signals from muscles of the ankle, knee, and hip. Participants walked using two cadences (52 and 78 steps/min) and two walking velocities (0.4 and 0.8 m/s). We observed phase-dependent modulation of vestibular influence over ongoing muscle activity in all recorded muscles. Within a stride, reversals of the muscle responses were observed in the biceps femoris, tibialis anterior, and rectus femoris. Vestibular-muscle coupling decreases with increases in both cadence and walking velocity. These results show that the observed vestibular suppression is muscle- and phase dependent. We suggest that the phase- and muscle-specific influence of vestibular signals on locomotor activity is organized according to each muscle's functional role in body stabilization during locomotion.

Hypergonadotrophic hypogonadism due to testicular adrenal rest tumours presenting with hypogonadotrophic hypergonadism.

Primary testicular failure is characterized by low serum testosterone with appropriately high serum gonadotrophins, that is hypergonadotrophic hypogonadism. We report on a 27-year-old man with congenital adrenal hyperplasia (CAH) and infertility due to testicular adrenal rest rumours (TART) resulting in primary testicular failure but presenting with azoospermia, elevated serum testosterone and very low serum gonadotrophins. Hypergonadotrophic hypogonadism was unmasked by increasing glucocorticoid dosage. It is important to recognise the limitations of follicle-stimulating hormone, luteinising hormone and testosterone in assessing testicular function in men with CAH. Abnormal semen analysis may be the best indicator of testicular dysfunction in men with CAH.

Extracting phase-dependent human vestibular reflexes during locomotion using both time and frequency correlation approaches.

Daily activities, such as walking, may require dynamic modulation of vestibular input onto motoneurons. This dynamic modulation is difficult to identify in humans due to limitations in the delivery and analysis of current vestibular probes, such as galvanic vestibular stimulation. Stochastic vestibular stimulation, however, provides an alternative method to extract human vestibular reflexes. Here, we used time-dependent coherence and time-dependent cross-correlation, coupled with stochastic vestibular stimulation, to investigate the phase dependency of human vestibular reflexes during locomotion. We found that phase-dependent activity from the medial gastrocnemius muscles is correlated with the vestibular signals over the 2- to 20-Hz bandwidth during the stance phase of locomotion. Vestibular-gastrocnemius coherence and time-dependent cross-correlations reached maximums at 21 ± 4 and 23 ± 8% of the step cycle following heel contact and before the period of maximal electromyographic activity (38 ± 5%). These results demonstrate 1) the effectiveness of these techniques in extracting the phase-dependent modulation of vestibulomuscular coupling during a cyclic task; 2) that vestibulomuscular coupling is phasically modulated during locomotion; and 3) that the period of strongest vestibulomuscular coupling does not correspond to the period of maximal electromyographic activity in the gastrocnemius. Therefore, we have shown that stochastic vestibular stimulation, coupled with time-frequency decomposition, provides an effective tool to assess the contribution of vestibular ex-afference to the muscular control during locomotion.

Short and medium latency muscle responses evoked by electrical vestibular stimulation are a composite of all stimulus frequencies.

Electrical vestibular stimulation produces biphasic responses in muscles maintaining balance. The two components of these muscle responses (termed the short latency and medium latency components) are believed to be independent and elicited by vestibular stimuli of different frequencies. We tested these hypotheses by determining (a) if frequency-specific stimulation protocols could evoke independently the short and medium latency responses and (b) whether these two components are triggered by distinct brain regions with a fixed time delay, interacting around 10 Hz. First, subjects were provided 10-25 Hz, 0-10 Hz, and 0-25 Hz vestibular stimuli to selectively modulate the short latency, medium latency, or both components of the response; and second, they were provided twenty sinusoidal stimuli from 1 to 20 Hz with a 0-20 Hz control trial, designed to determine whether an interaction between the short and medium latency responses occurs at a specific stimulation frequency. Both the 0-10 Hz and 10-25 Hz vestibular stimuli elicited multiphasic waveforms, suggesting the short and medium latency components were not modulated independently by the frequency-specific stimuli. Sinusoidal vestibular stimuli evoked responses at the stimulated frequency but no evidence of a reflex component interaction was observed. Instead, summation of the responses evoked by each of the sinusoidal stimuli resembled the biphasic response to broad bandwidth stimuli. Due to the lack of interaction and linear contribution of all stimulus frequencies to both the short and medium latency responses, the present results support the use of broad bandwidth electrical vestibular signal for physiological or clinical testing.

Frequency-specific modulation of vestibular-evoked sway responses in humans.

Galvanic vestibular stimulation (GVS) results in characteristic muscle and whole-body responses in humans maintaining standing balance. However, the relationship between these two vestibular-evoked responses remains elusive. This study seeks to determine whether mechanical filtering from conversion of lower-limb muscle activity to body sway, during standing balance, can be used to attenuate sway while maintaining biphasic lower-limb muscle responses using frequency-limited stochastic vestibular stimulation (SVS). We hypothesized that SVS deprived of frequencies <2 Hz would evoke biphasic muscle responses with minimal whole-body sway due to mechanical filtering of the higher-frequency muscle responses. Subjects were exposed to five stimulus bandwidths: two meant to induce sway responses (0-1 and 0-2 Hz) and three to dissociate vestibular-evoked muscle responses from whole-body sway (0-25, 1-25, and 2-25 Hz). Two main results emerged: 1) SVS-related sway was attenuated when frequencies <2 Hz were excluded, whereas multiphasic muscle and force responses were retained; and 2) the gain of the estimated transfer functions exhibited successive low-pass filtering of vestibular stimuli during conversion to muscle activity, anteroposterior (AP) moment, and sway. This successive low-pass filtering limited the transfer of signal power to frequencies <20 Hz in muscle activity, <5 Hz in AP moment, and <2 Hz in AP trunk sway. Consequently, the present results show that SVS delivered at frequencies >2 Hz to standing humans do not cause a destabilizing whole-body sway response but are associated with the typical biphasic lower-limb muscle responses.

Short-duration galvanic vestibular stimulation evokes prolonged balance responses.

The application of galvanic vestibular stimulation (GVS) evokes distinct responses in lower limb muscles involved in the control of balance. The purpose of this study was to investigate the balance and lower limb muscle responses to short-duration GVS and to determine whether these responses are modulated by small changes in center of gravity (CoG) and baseline muscle activity occurring during quiet standing. Twelve subjects stood quietly on a force plate with their feet together and were instructed to look straight ahead. One thousand twenty-four GVS stimuli (4 mA, 20-ms pulses) were delivered bilaterally to the mastoid processes in a bipolar, binaural configuration. Bilateral surface electromyography (EMG) from soleus (Sol) and tibialis anterior (TA) and ground reaction forces were recorded. EMG and force responses were trigger averaged at the onset of the GVS pulse. Short-duration GVS applied during quiet standing with the head facing forward evoked characteristic balance responses and biphasic modulation of all muscles with the same polarity for ipsilateral Sol and TA. The amplitude of the GVS-evoked muscle responses was modulated by both the estimated position of the subject's CoG and the background activation of the recorded muscle. Muscle-dependent modulations of the GVS-evoked muscle responses were observed: the Sol responses decreased, while the TA responses increased when the CoG position shifted toward the heels. The well-defined balance responses evoked by short-duration GVS are important to acknowledge when studying the vestibulo-motor responses in healthy subjects and patient populations.

Investigation of acute flank pain: how do practices of U.K.and Irish urologists compare with those of transatlantic and continental European colleagues?

BACKGROUND AND PURPOSE: Noncontrast-enhanced spiral CT (NESCT) is more accurate and reliable than intravenous urography (IVU) in diagnosing the cause of acute flank pain. This study aimed to determine the impact of current literature on the choice of imaging modality used to investigate acute flank pain within the UK and the Republic of Ireland. MATERIALS AND METHODS: A questionnaire regarding the preferred investigation for acute flank pain was sent to all consultant urologists registered as British Association of Urological Surgeons members. RESULTS: Of the 548 consultants from 210 institutions surveyed, 293 (54%) from 171 (81.4%) institutions returned their questionnaires. Intravenous urography is used in the majority of institutions (146; 85.4%) for investigating acute flank pain. Only 18 (10.5%) use NESCT, while 4.1% use ultrasonography. Among those using IVU as the investigation of choice, the main reason given was limited CT services (82.4%). Others included familiarity with IVU features (51.2%), limited availability of radiologists for out-of-hours reporting of CT (26%), more rapid procedure (20.8%), lower cost (20%), and lower radiation exposure (19.6%). Only 52.4% of consultants using IVU would prefer NESCT if both were equally available. CONCLUSIONS: Urography remains the commonest modality for the investigation of acute flank pain in the UK and Ireland primarily because of limited CT services and greater familiarity with the images. Given the opportunity, only half of consultant urologists would select NESCT in preference to IVU, suggesting that improving the availability of CT services alone may not lead to practice paralleling that of our transatlantic and continental European colleagues.