The subject of climate feedbacks focuses attention on global mean surface air temperature (GMST) as the key metric of climate change. But what does knowledge of past and future GMST tell us about the climate of specific regions? In the context of the ongoing UNFCCC process, this is an important question for policy-makers as well as for scientists. The answer depends on many factors, including the mechanisms causing changes, the timescale of the changes, and the variables and regions of interest. This paper provides a review and analysis of the relationship between changes in GMST and changes in local climate, first in observational records and then in a range of climate model simulations, which are used to interpret the observations. The focus is on decadal timescales, which are of particular interest in relation to recent and near-future anthropogenic climate change. It is shown that GMST primarily provides information about forced responses, but that understanding and quantifying internal variability is essential to projecting climate and climate impacts on regional-to-local scales. The relationship between local forced responses and GMST is often linear but may be nonlinear, and can be greatly complicated by competition between different forcing factors. Climate projections are limited not only by uncertainties in the signal of climate change but also by uncertainties in the characteristics of real-world internal variability. Finally, it is shown that the relationship between GMST and local climate provides a simple approach to climate change detection, and a useful guide to attribution studies. GMST is also the central metric around which UNFCCC discussions of mitigation policy are based. However, GMST is a remote concept to most people. Fundamentally, it is changes on regional and local scales that affect people directly. Knowledge about changes on these smaller scales is essential for the development of robust adaptation strategies, and is also required by national policy-makers when debating mitigation options. From these considerations follows a simple but important question: what does knowledge of past and future GMST tell us about local climate?The issue of the relationship between changes in GMST and other aspects of a changing climate has recently gained prominence in discussions of the so-called ‘pause’ or ‘hiatus’ in global mean surface temperature rise –4. Over Another example is provided by The aim of this paper is to explore more systematically the relationship between changes in GMST and changes in local climate in different parts of the world. To do so requires consideration of both the internal variability in the climate system and the response of the climate system to changing forcing, such as that caused by the rapid increase in greenhouse gas concentrations in the atmosphere. Climate model simulations are used to separate the contributions from these two factors, and to explore their combination in reality. The structure of the paper is as follows. Section 2.We examine historical variations in surface air temperature (SAT) using data from the Berkeley Earth Surface Temperature (BEST) project . BEST an1 As we will discuss later, this is an interesting and far from obvious result  over land areas than sea areas. Higher values are also found in the Arctic and in the South Atlantic and southern Indian Oceans. Two regions where low values are found stand out: the subpolar North Atlantic and the Indian Ocean east of Madagascar. In both of these regions GMST accounts for less than 20% of the variance on decadal timescales. The North Atlantic region has been described as a ‘warming hole’ . Figure in situ data were available for this region, which suggests that this warming may not be real, and that the apparent differences from the evolution of GMST are similarly unreliable. These data issues merit further research.Inspection of the SAT time series for the Indian Ocean region shows an abrupt warming in the late 1940s (not shown), which is not seen in GMST. However, this is a period when very little Further interpretation of the observational results shown in 3.Internal variability refers to fluctuations in climate that arise from instabilities in one component of the climate system (e.g. baroclinic instability in the atmosphere or ocean) or from interactions between different components . These fluctuations arise even in the absence of any change in forcing. Some internal variability (of which ENSO is an example) causes significant fluctuations in GMST, but most does not. However, internal variability plays a central role in explaining climate variability on regional and smaller scales ,19.On interannual and shorter timescales, internal variability exhibits some preferred timescales . It is not known whether preferred timescales of internal variability also exist on decadal or longer timescales. There is undoubtedly memory in the oceans and land surface  on decadal-to-centennial timescales, and memory in the cryosphere extends to much longer timescales, but it is unclear whether such memory leads to significant peaks in the power spectrum of internal variability or merely causes a broader enhancement of power at low frequencies (i.e. reddening the power spectrum).after detrending) and also differ in the shape of their power spectra. Some models (e.g. GFDL-CM3) show evidence of preferred timescales while others do not. The magnitude of internal decadal variability in GMST is influenced by climate feedbacks, and is directly relevant to understanding events such as the recent ‘hiatus’ in GMST rise, discussed in §The study of internal variability on decadal and longer timescales is hampered by short observational records and difficulties in separating internal variability from forced signals in the face of substantial uncertainties in both forcings and responses. Climate model simulations offer an alternative approach to study internal variability in more controlled circumstances, but a difficulty here is that different models show surprisingly diverse behaviour ,21. Figu— In all models, over most of the planet, GMST accounts for less than 20% of the variance in local SAT on decadal timescales . This finding is consistent with our expectation that most internal variability is unrelated to GMST.— The regions where GMST accounts for more than 50% of the variance in local SAT differ substantially between models. For example, in some models the relevant regions are found in the tropics, while in other models higher latitudes dominate . This fiRegression analysis can be used to identify the spatial patterns of climate change that are related to internal variability in GMST . Applica4.To compare cleanly the forced responses simulated by different climate models it is necessary to remove, or minimize, the effects of internal variability. Where they are available ensemble simulations, in which individual ensemble members differ in their realization of internal variability, provide a very valuable resource ,24. In pA comparison of The patterns of forced response in precipitation change show much greater diversity between models than is the case for SAT change . This ‘rnot imply no change in climate. On the contrary, different forcings may lead to substantially different patterns of regional climate change [e change ,36. So, e change . The cone change . Note th5.In the real world, the forced response of anthropogenic climate change is gradually emerging from the background of natural internal variability. At the local scale, internal variability is the dominant factor in people’s experiences of day-to-day and year-to-year variations in the weather. Individuals and societies are adapted to a certain level, or range, of weather variability that is characteristic of the places where they live, and the same is true of natural ecosystems. It is when climate change leads to weather or climate events that are outside of this familiar range of experience that large and costly impacts typically arise ,40. ThesThe relative importance of the forced climate response and internal climate variability, and hence the emergence of the signal of climate change, depends on several factors: the variable of interest, the spatial scale, the temporal scale, and the time horizon . We have2 concentration. For a single simulation, over a time horizon of 140 years GMST accounts for 80% or more of the variance in local SAT over most of the planet. By contrast, over a time horizon of 20 years GMST accounts for less than 40% of the variance. The exact proportion will depend on the model examined, but an important robust result is that, on timescales of a few decades, at the local scale internal variability can easily dominate the forced response [response ,19. Thisresponse ), with tresponse ,43.FiguThe value of GMST as a predictor of local climate has relevance to detection and attribution of climate change . As was Detection analysis does not identify which specific changes in forcing may have caused the observed climate change (the attribution problem), but ruling out internal variability as the sole or dominant cause is an important step. In addition, comparing local changes in climate on decadal timescales with changes in GMST provides a very simple approach to identify regions where particularly careful attention in attribution research may be required, as is undoubtedly the case for the NASPG region, discussed in §§6.net) forced change in GMST, a fact which is crucial to the assessment of geo-engineering proposals.The value of GMST as a predictor of regional changes in climate depends on the relative importance of forced responses and internal variability, which depends in turn on the variable of interest; the spatial scale; the time scale; and the time horizon. Internal variability is increasingly important at smaller space and time scales and for shorter time horizons. It is also more important for mean precipitation than for SAT. In the absence of any forced climate signals , GMST explains only a small fraction of the variance in local climate . In the case of a pure forced signal, if the response is linear then GMST necessarily explains 100% of the variance in local climate. However, nonlinear responses to greenhouse gas forcing are known to exist, and are expected to be important in specific regions such as the North Atlantic Subpolar Gyre. Furthermore, competition between multiple forcings (e.g. greenhouse gases and anthropogenic aerosol) complicate the relationship between changes in GMST and changes in local climate. An important consequence is that large forced changes in regional climates may occur in the absence of any  is important for the assessment impacts and changing risks. Projections of emergence are limited by significant uncertainties in both the climate change signal on local scales (response uncertainty) and uncertainties in the characteristics of internal variability. Large differences in the latter characteristics have been found in comparisons between different climate models. For some applications, uncertainties in internal variability may be as important as the uncertainties in climate feedbacks.In an analysis of observational records, it has been shown that GMST explains 60%, or more, of the variance in local SAT on decadal and longer timescales over a large fraction of the planet. When considered in the context of other findings, this result implies that decadal changes in SAT over the instrumental record have been substantially shaped by a forced response. Thus analysing the relationship between GMST and local climate provides a simple approach to climate change detection, and a useful guide to attribution studies.


Subjective tinnitus is the perception of sound in the absence of a corresponding external sound for which there is no known medical etiology. For a minority of individuals with tinnitus, the condition impacts their ability to lead a normal lifestyle and is severely debilitating. There is no known cure for tinnitus, so current therapy focuses on reducing the effect of tinnitus on the patient’s quality of life. Tinnitus retraining therapy (TRT) uses nonpsychiatric tinnitus-specific educational counseling and sound therapy in a habituation-based protocol to reduce the patient’s tinnitus-evoked negative reaction to, and awareness of, the tinnitus, with the ultimate goal of reducing the tinnitus impact on the patient’s quality of life. Some studies support the efficacy of TRT, but no trial to date has compared TRT with the current standard of care or evaluated the separate contributions of TRT counseling and sound therapy. The Tinnitus Retraining Therapy Trial (TRTT) is a randomized, double-blind, placebo-controlled, multicenter trial for individuals with intolerable tinnitus.The TRTT is enrolling active-duty and retired military personnel and their dependents with functionally adequate hearing sensitivity and severe tinnitus at US Air Force, Navy, and Army medical centers. Eligible study participants are randomized to TRT, partial TRT, or standard care to determine the efficacy of TRT and its components (TRT counseling and sound therapy). The primary outcome is change in score on the Tinnitus Questionnaire assessed longitudinally between baseline and follow-up . Secondary outcomes include subscale score changes in the Tinnitus Questionnaire, overall and subscale score changes in the Tinnitus Functional Index and Tinnitus Handicap Inventory, and change in the visual analog scale of the TRT Interview Form. Audiological outcomes include tinnitus pitch and loudness match and measures of loudness discomfort levels. The incidence of depression as a safety measure is assessed at each visit using the Beck Depression Inventory Fast Screen.NCT01177137.Clinicaltrials.gov Tinnitus is the perception of sound in the absence of a corresponding external sound for which there is no apparent cause. The precise mechanisms underlying subjective tinnitus are currently unknown. Almost everyone experiences some degree of tinnitus at some time, including sensations of ringing, buzzing, whistling, or hissing. The majority of persons experiencing tinnitus do not report undue distress associated with the tinnitus or require professional help. The prevalence of continuous subjective tinnitus among adults ranges from 10.1 to 14.5% significant change’, . An effect size of 0.8 to 1.0 on the full Tinnitus Questionnaire would correspond to a change of approximately 10 to 13 points. Wolfgang Hiller, a researcher with extensive experience with the Tinnitus Questionnaire stated, ‘A change of less than 5 to 6 points does not mean much’, . Based on these considerations, we chose to design the TRTT with sufficient power to detect a ten-point difference for the primary comparison  and a seven-point difference for the secondary comparisons . We assumed a type-I error rate of 0.05, using a two-sided test and 80% power for the secondary comparisons. We further assumed that a standard deviation of 12.5 would hold for all groups and that there would be 10% attrition. Accordingly, by dividing an α of 0.05 among the three comparisons and accounting for 10% attrition, we estimated that a total of 228 study participants (76 participants in each of the three groups) will be required to yield at least 80% power to detect a seven-point difference for analyses of the TRT components, sound therapy and TRT counseling. This saThe TRTT clinical center staff collect study data on paper data collection forms and enter data online using the TRTT website. All data items are validated against criteria specified in the data dictionary, including checks for consistency with other responses and completeness during data entry. Data errors or inconsistencies are flagged and displayed immediately online during the data entry process. Data flags require ‘immediate correction’ or may be set as ‘warnings’ (missing data). Flags that require ‘immediate correction’ do not permit submission of the form without correction. Warnings will not disallow submission of the form, but must be addressed in a timely manner. Warnings are entered into an error log, and an error report is produced by the system. Any variables that are marked as possibly in error are reported to the clinical centers. In addition, errors are detected by data coordinating center staff during routine audits, in which data on copies of paper data collection forms are compared with data already entered into the database. Sites make corrections in the TRTT website database or verify that the information entered is correct. Any new errors generated during editing are added to the error log. Immediately following completion of entry of all expected data collection forms for an individual study participant, a set of cross-form and cross-visit data queries will be run and the clinic queried for inconsistencies detected. Official interim datasets, containing data entered ‘as of’ a given date, are created for monitoring purposes in conjunction with data and safety monitoring board interim report generation. These datasets are archived for reference in duplicate analysis.Security measures include password protection for each user who is granted privileges; access is based on ‘need to know’. All elements of the database are backed up daily and weekly onto high-capacity cassette tapes, and monthly backups are transferred to CD media. In addition to data kept on site, copies of weekly backups are stored off site in a fireproof safe.Initial analyses will be descriptive in nature, using means, standard deviations, and proportions to describe baseline characteristics of the study participants, both combined and by intervention group. Distributions of continuous variables will be examined for symmetry, and transformations will be considered for seriously skewed variables. For continuous variables, one-way analysis of variance will be used to compare intervention groups on demographic and other baseline characteristics. For dichotomous or other categorical variables, chi-square tests will be used to compare intervention groups, and enrolled and excluded groups. Pearson correlation coefficients will be calculated to assess the strength of the associations among the various outcome measures and to examine associations of other covariates with outcome measures; potential confounding variables will be considered for inclusion in secondary analyses involving regression models.The primary outcome variable will be change in the Tinnitus Questionnaire score, using spaghetti plots for initial exploratory analyses and longitudinal data analyses for the primary analytic method. Indicator variables will identify treatment group, with coefficients in the models representing the primary focus on group differences. Mean Tinnitus Questionnaire scores will be compared between two treatment groups using generalized estimating equations. The basic model will account for effects of clinical center, treating audiologist, treatment group, and, possibly, personality traits, as measured by the State-Trait Anxiety Index or Positive and Negative Affect Schedule. Other factors that might be included are scores from the Hearing Handicap Inventory or early completion of treatment. Similar models will be run for the secondary objectives. These variables in the models will be used to estimate the relation between various personality characteristics and successful habituation to tinnitus. Interaction terms between these participant characteristics and treatment groups will be included, to assess whether the effect of TRT is greater for certain types of participant. Similar analyses will assess whether age, sex, or other participant characteristics are predictive of successful habituation with or without TRT.For the secondary efficacy analyses, we will compare Tinnitus Questionnaire mean scores at 18-months follow-up (end of treatment) among treatment groups using analysis of covariance, adjusting for baseline Tinnitus Questionnaire scores and heterogeneity of tinnitus status in the study population. We will also adjust for important baseline covariates and variables that may be unbalanced at baseline and potentially related to Tinnitus Questionnaire score. We will also use generalized estimating equations for this analysis.We will use this approach with other outcome variables, including the Tinnitus Questionnaire subscales, global and subscale scores of the Tinnitus Functional Index, Tinnitus Handicap Inventory, and visual analog scale of the TRT Interview Form. We will also compare baseline audiometric measures, psychoacoustic variables of tinnitus pitch and loudness match, and loudness discomfort levels to evaluate change across time in these measures.All analyses will be based on the principle of intention to treat  regardless of whether they adhered to, or completed, the assigned treatment. For the primary outcome, the only participants who will not be included will be those for whom Tinnitus Questionnaire could not be assessed at any follow-up visit due to loss to follow-up. However, we anticipate that few, if any, participants will be unable to complete at least one follow-up Tinnitus Questionnaire measure. To account for missing values, we will use multiple imputation, which assumes that missing data are missing at random.Organizational units of the TRTT include a study chair’s office, a data coordinating center, clinical centers, and various committees. The National Institute on Deafness and Other Communication Disorders (NIDCD) at the National Institutes of Health funds the TRTT through a cooperative grant arrangement and provides a project officer. Leadership in the TRTT is shared by the study chair and the director of the data coordinating center.The chair’s office is responsible for the overall scientific and administrative aspects of the trial. Study personnel at the chair’s office include the study chair, TRT and standard care training and protocol monitors, a human research protocol monitor, and an administrative assistant. The chair’s office is responsible for supervision of the overall study by integrating the activities of the data coordinating center and clinical centers, including recruitment and oversight of the clinical centers. The chair’s office provides assistance to clinical centers on protocol implementation and monitors clinical center institutional review board approval. It is charged with resolution of all technical and scientific questions regarding clinical training and treatment issues and complications. The study chair organizes and conducts TRT and standard care training sessions. Together with the data coordinating center, the study chair implements quality assurance measures to monitor treatment adherence in TRTT clinical centers. The data coordinating center oversees scientific aspects of study design, and serves as the focus of study communications, training, and certification of clinical staff in trial procedures, protocol interpretation, data processing, data analysis, and quality assurance activities. Staff at the data coordinating center include the director, biostatistician, director of information management, database programmer, statistical programmer or analyst, project coordinator, and research assistants. The data coordinating center prepares, maintains, and distributes study documents, data collection forms, and a web-based data system to process data with computer-based randomization schedules for each clinical center. The data coordinating center trains clinical center staff on the study protocol, supervises TRTT data collection and processing, and performs all study analyses. Quality control and assurance responsibilities include certification of clinical center staff and routine monitoring of recruitment, data processing, and adherence to study protocol. The data coordinating center is the official TRTT archive for all study data, and will prepare a public use data set of TRTT data.Clinical center staff include at least two audiologists, a coordinator, an otolaryngologist, or study physician, and a data system operator. Clinical centers are responsible for participant recruitment, treatment administration, and follow-up according to study protocol. Data management activities at participating clinics include proper completion of all data collection forms, transmission of that information to the data coordinating center using the TRTT website accurately and timely, and responses to requests for data clarification or correction.The TRTT has three primary standing committees: a steering committee, an executive committee, and a data and safety monitoring board.Members of the steering committee include the study chair, data coordinating center director, biostatistician, clinical center directors, and NIDCD project officer. The steering committee is responsible for the review and approval of trial procedures, resolution of technical or operational issues, review of study progress and approval of major changes to the study protocol. The steering committee is also responsible for acting on advice from the data and safety monitoring board, appointment or termination of subcommittees, review and approval of ancillary studies, and oversight of publication of study findings.The executive committee includes the study chair, data coordinating center director, and NIDCD project officer, and is responsible for implementation of decisions made by the steering committee and matters affecting the day-to-day operations of the trial.The data and safety monitoring board is responsible for ensuring participant safety and monitoring the overall performance of the trial. This board reviews the study data, as they are collected, for evidence of harmful or beneficial treatment effects. The members of this committee, appointed by the NIDCD, include a chair and three additional voting members not affiliated with the study. This committee is the only committee provided with evidence of treatment effects while the study is still in progress. The data and safety monitoring board usually meets twice a year, but additional meetings are scheduled as necessary.All TRTT papers that describe the main results of the TRTT  will follow corporate or group authorship format, naming ‘The Tinnitus Retraining Therapy Trial Research Group’ as author, with individual investigators and clinical center staff acknowledged. No comparison data will be available prior to completion of the study and no clinic may publish data obtained from their clinic independently. Writing committees for TRTT papers will include at least one representative from the chair’s office, one from the data coordinating center, and other study group members based on interest and expertise. All TRTT manuscripts will be submitted to journals complying with the National Institutes of Health Public Access Policy, and all publications will be archived in PubMed Central, as required by this policy. Presentations at conferences describing or presenting TRTT results follow the same guidelines and require clearance by the steering committee.The TRTT data will become available to outside investigators at the conclusion of the trial and following publication of the main study findings. To protect the confidentiality of participant data, only de-identified data will be made available for secondary analysis. All secondary users of data will be asked to sign a data use agreement that stipulates: confidentiality and data security standards must be adhered to by the recipient; data are to be used for research purposes approved by the institutional review board only; no effort will be made to identify individual participants; and data will not be transferred to other users by the recipient.This report describes a randomized clinical trial that will determine the efficacy of TRT and its component parts, tinnitus-specific educational counseling and sound therapy, compared with standard care, in a military population. Two features of the study highlight efficiency in design. First, we designed the trial with three arms; two arms differ only by whether placebo or conventional sound generators are used and the third arm is standard care. This design allows us to make multiple comparisons and parse out the separate effects of the TRT components. In addition, we are conducting the study in US military hospitals. We chose to conduct the study in this setting given the higher prevalence of tinnitus among individuals exposed to intense noises. Because the military population is similar to the general population in all other aspects, we believe that the study results will be generally applicable.Because the TRTT is assessing tinnitus-specific health-related quality of life using three commonly used instruments , we will be able to assess comparability across these instruments. We will also assess whether the Digit Symbol Substitution Test is a useful measure to assess the ability to concentrate in individuals with tinnitus.A unique feature of the TRTT is the development of a standardized protocol for both TRT and standard care, as practiced in the military for persons suffering from severe tinnitus. The TRTT developed a standardized tinnitus-specific educational counseling component of TRT, comprised of scripts, a flipchart, and visual aids to be used by all audiologists at all clinical centers. This standardized treatment protocol allowed different audiologists across military centers to learn and administer TRT as a treatment for severe tinnitus not only within the trial, but in their clinical practices. In addition, the TRTT investigators engaged the assistance of General Hearing Instruments, Inc., in the development of a placebo sound generator, enabling measurement of the separate effects of the component parts of the TRT intervention, tinnitus-specific educational counseling and sound therapy. Both placebo and conventional sound generators can be used to assess participant compliance by recording times when the device is worn or not worn. This ability provides for the monitoring of treatment fidelity. The TRTT investigators also developed a standard care protocol to achieve uniformity in the care of tinnitus by surveying clinical centers before the trial began and incorporating current guideline recommendations. StandarThe TRTT is currently in the process of recruiting study participants.


Urethral stricture is one of the most difficult urological problems to heal adequately and many surgical and no surgical techniques have been described to its management. Reports has been documented in ancient literature of the Hindus, Egyptians and Greeks . In 1957Since this description by Sachse, the direct vision internal urethrotomy (DVIU) became one of the most popular treatments on the management of urethral strictures. The male anterior urethra stricture is characterized by a fibrotic process which achieves varying degrees of peri-urethral spongiosum tissue fibrosis (spongiofibrosis) associated with a decrease in urethral caliber and consequently in the urine flow. Endoscopic treatment is based on the deep incision of the fibrotic area and subsequently local reepithelization process to the maintenance of the urethral patency.Data from the National Health Service in the UK during 2006 showed that the DVIU or urethral dilatation was used in 93% of cases and urethroplasty in 7% of cases . In a naDuring the 80's and 90's decades, many authors have published very interesting rates of success for the endoscopic management of anterior urethral strictures and helped to popularize this method in this period. Even in cases of complete obstruction of the urethral, with intense spongiofibrosis, the use of the DVIU was postulated by some authors. Publications demonstrating a success rate up to 77% on 369 procedures performed in 225 patients  follow-up –10 risk More recently, Santucci et al. presented lower success rates for the DVIU. In this study, the success rates were no higher than 9% for first or subsequent urethrotomy during the observation period .As a treatment for male urethral stricture, internal urethrotomy has the advantages of ease, simplicity, speed and short convalescence. Despite that, some rate of complications is associated to the procedure– erectile dysfunction, penile curvature, bleeding, urinary tract infections and priapism –11.Various modifications of the classic single cold-knife incision in the 12 o'clock position have been proposed, including multiple radial incisions. Another point, is the post operative period with the urethral catheter. In both, number or position of the incisions and time of catheterization, the publications are usually retrospective case-series and there are no good prospective, randomized studies to prove their claims of greater efficacy. Our personal preference is to use multiple radial incisions (between 3–5) to improve the reepithelization area and leave a silicon catheter for 3 days only. In a survey with American Urologic Association members, the majority of the urologists leave the catheter around one week .In recent decades several authors have published more significant changes in technique, mainly related to new forms of energy and the use of anti-fibrotic agents.Lasers have been used for the treatment of urethral strictures since 1977. The types used for urethrotomy include carbon dioxide, Nd: YAG, the KTP, the Argon, the Ho: YAG and excimer lasers . In anotThe use of various anti-fibrotic substances during the endoscopic procedure have also been describe by many authors - corticosteroids, botulinum toxin, hyaluronic acid, captopril gel and mitomycin C among others. A systematic review showed that the use of local corticosteroid may prolong the time to recurrence of stenosis after a DVIU but not seem to affect the final rate of recurrence . Kim et In our practice we found that ultrasound can be used as a complementary method to the retrograde and voiding urethrogram in selecting patients for an internal urethrotomy. This method can provide more accuracy in defining the length and location of the stricture segment and can add information about the degree of spongiofibrosis and the urethral caliber. The proper selection and characterization of patients seems to be essential to achieve better results with the internal urethrotomy.A common practice among urologist, is the use of sequential dilatation protocols after the DVIU, which can reduce the chance of failure, as described in some papers . From thWright et al. indicated that the most cost-effective management algorithm for a bulbar urethral stricture of <2 cm is a single internal urethrotomy followed by urethroplasty if the urethrotomy fails . Rourke In the group of patients selected to have the best results for the internal urethrotomy  the results observed to the urethroplasty still seems to be more effectives. Failures for urethroplasty, in this group, will be an uncommon event. Excision with primary urethral anastomosis has a high success rate with durable long-term results in most patients and the complications are rare with short duration and self-limited. , 10, 11.The DVIU can also be an option in the initial management of localized failures after urethroplasty, including procedures with tissue substitution (grafts and flaps). In a retrospective study, Rosenbaum et al observed that about half of patients with re-strictures <1 cm after uretroplasties with buccal mucosa grafts (BMG) can be treated with a internal urethrotomy without new failures in a mean follow-up of 11.7 months .In our practice we consider to offer internal urethrotomy for selected cases as first surgical alternative - bulbar, short (<1 cm) and non-traumatic . All patients should be informed about the low success rates in the long term follow-up with this procedure and the possibility to be submitted to procedures with more definitive results as anastomotic urethroplasty or substitution urethroplasty. We do not offer a second urethrotomy as an option after an initial failure. The internal urethrotomy may also be used as a optional technique in some patients with post urethroplasty failures and even in patients with high surgical risk for a more aggressive procedures.Urethral dilatation and DVIU remain widely used in urethral stricture management but high-level comparative evidence of benefit and harms against urethroplasty in the short and long-term is still lack.


The obesity epidemic is rapidly advancing in South America, leading to inevitable health consequences. Argentinian and Brazilian health policies try to become adapted to the new economic and social framework that follows from this epidemic. It is in incipient and ineffective control so far since the prevalence of obesity was not restrained. The Argentine national legislation is more advanced, through the so-called “Ley de Obesidad.” In Brazil, there are numerous local initiatives but still not a comprehensive law. National policies relating to decisions regarding obesity are discussed in this paper. Trends in decisions issued in higher courts of Argentina (Supreme Court of Justice of the Nation—CSJN) and Brazil (Supreme Court of Justice—STF), in the last 15 years, seek to clarify the approach of each country and court's resolutions. Marked differences were found in their positions. Finally, legal and health solutions to this obesity epidemic are proposed. Obesity is a worldwide health and sociopolitical problem. Excessive body-weight currently affects over 50% of the Brazilian and Argentinian populations. This picture is similar to other countries in the world nowadays ,2. Only 2] and 14.8% were obese (BMI over 30 kg/m2). Regarding gender, 40.3% of females and 59.7% of males were overweight. Among adults, the largest percentage of overweight persons was found in people between 35 and 64 years of age; In Brazil, a study done by the Ministry of Health ; both have a presidential government system, a still-inadequate income distribution, and belong to the same commonwealth of Mercosur. They share a parliament for the Mercosur and many common laws and health initiatives. They represent, indeed, the two most important economies and countries of South America. In both nations, there are three echelons of litigation: first (entrance level), second, and third (higher) level courts. Issues of national interest involving the country's health policies and constitutional matters can reach the highest level, represented in Brazil by the Supreme Court of Justice (STF) and, in Argentina, by the Supreme Court of Justice of the Nation (CSJN). In this way, judicial decisions can influence government policies towards health ,15. EquaLitigation can also be a useful strategy to advancing social rights in developing countries. Juridical decisions may influence public policies, leading to important political and economic consequences  as shownIn Brazil, the Public Healthcare System (a.k.a. as ‘SUS’) has control over public health. Since the adoption of the last constitution, as of 1988, all former health systems have been merged and placed under its auspices. SUS reaches the entire population but suffers from some obvious limitations, such as a low ‘per-capita’ investment and limited support for 190 million users. In Argentina, three different health systems exist , each with different rules. This division of authority makes it more difficult to achieve an ideal management. Therefore, rules that apply to all three systems are often necessary, such as the ‘Ley de Obesidad’ , a subordinate agency of the Ministry of Health, was a milestone in this process ,21. ArguIn 2008, Argentina approved a national obesity law. Argentinian Federal Law No. 26.396 of 3 September 2008  establishes a national policy for and approaches to the prevention of obesity . This laIn Brazil, Article 196 of the Constitution dictates that health issues are the responsibility of local and municipal governments. Brazil took initiatives at the municipal but not at the national level. Many municipalities have joined the project ‘Lighter City’ (‘Cidade Mais Leve’) by approving laws that deal with the needs of overweight and obese patients and citizens .Compared to other legal demands, the superior courts in Brazil and Argentina still handle the obesity issue as a secondary matter. The study of judicial decisions over the past decade shows markedly opposing interpretations in the two countries. In Brazil, there is a tendency to understand obesity as a disease that deserves attention since it impairs the health of those who suffer from it; obesity is, thus, considered a type of ‘physical disability’. Conversely, in Argentina, it is regarded as a relative condition, balanced in relation to the context and the subject, taking into account factors other than obesity itself. Therefore, obesity is associated with frailty in Brazil while it is seen as a single, though not decisive, factor in judicial decisions in Argentina.The aim of this paper is to analyze and understand the impact of obesity-related public health policies in Brazil and Argentina's legal systems. The decisions of the higher law courts of those countries are studied. Medicine, law, and public health share interests on the obesity epidemic.2). A BMI greater than or equal to 25 indicates overweight while one greater than or equal to 30 specifies obesity, and one of 40 or more implies severe obesity.Overweight and obesity are defined as “abnormal or excessive fat accumulation that may impair health” . The bodThe main review was conducted using the search engines of the websites of the superior courts of Brazil and Argentina, using the key word ‘obesity’ to select the decisions in which this term was mentioned. The entire content of the juridical decisions was accessed, which means that the final decision and report, signed by the members of the courts, were analyzed and described for a better comprehension of the understanding of the legal authority on that matter. For the medical and juridical reviews of the obesity issue, searches were conducted for the academic literature on law and medicine and for online sources in Google Scholar, PubMed, Medline, juridical web pages, books, and law doctrines. The constitutions and national laws of Brazil and Argentina were examined to identify trends in their approaches to obesity. Principles of Law, such as the principle of human dignity and of the protection of law, present in both constitutions, were analyzed in the context of obesity. In Latin America today, specific legislation is almost always founded on the principles of law. The sources of data search, including constitutions, laws, and doctrines are described in Obesity is now regarded not only as a single health matter but shows also social implications. Therefore, applicants request their rights in social demands when obesity impairs their working and social capacities. The methods of this study include the analysis of these social demands, looking for trends and facts to embase and explain the reasons why health courts and other law courts have to judge increasing obesity demands on private civil rights.The content of the decisions of the ministers and courts and the specific approach of each jurist were studied in order to identify the principal methods used in resolving conflicts and addressing the issue of obesity. The decisions of judges always should rely on existing laws and reflect the principles of law and relevant specific situations. The highest courts of both countries were studied, that is, those that possess the right to interpret the laws in search of the best juridical ends.A qualitative analysis of the votes of each magistrate was used for conceptualizing the obesity issue. The analysis involved cases dealing with (i) authorization of clinical or surgical procedures, which usually depended on given court decisions and (ii) decisions relating to the social rights of the defendants. These latter decisions are described in Ten cases involved obesity over the last 15 years.Four were related to the treatment of disorder .Six cases were referred to the social dignity of obese applicants . These cThe second case was referred to the lack of structure of the health institution to deal with the obese patient seen. This patient had an excess weight and required the special technical care that obesity demands: special beds, sphigmomanometers, specialized care; and other health apparatus which were not available at the hospital, although these were covered by the Argentinian ‘Ley de Obesidad’.The 3 cases referring to retirement were analyzed separately according to each personal situation. One person had debts to pay and alleged to be obese but the court did not accept this explanation. In the other 2 cases, the court accepted the demand because the patients had obesity and associated morbidities which impaired their working capacity.The survey found 11 obesity-related jurisprudential decisions and one monocratic decision by the president of the Supreme Court.Six cases concerned to the costs of the treatment for the disorder. Remarkably, all but one of the latter regarded the funding of bariatric surgeries, a hot topic on treatment for obesity these days because of its shown long-term efficacy. The Brazilian court always permitted this procedure—in all 5 referred cases described in Six other cases concerned the right to social dignity of obese persons. Those showed different patterns, heterogeneous arguments, reasons, and facts. The decisions of the six cases relating to the social dignity of people with obesity are outlined in Two cases were referred to candidates to the Air Force and the Police Department. Both candidates were obese and demanded approval at the physical test, despite their condition because they sufficiently performed the logics and reasoning theory tests, having achieved high grades on those latter topics. The security forces forcefully require not only approval on theory tests but also demand specific physical conditions for acceptance because of the critical conditions of some of their job positions, such as a pilot's and a policeman's daily physical procedures. The court's decisions on both cases positioned for the special forces. The judges understood that the Principle of Equality on a contest demands the contest's bidding and purpose to be followed and should also respect the working conditions demanded from each candidate .An important case in 2001 was referred to a request of comfortable seats on cultural events at the municipality of Curitiba–Paraná (Brazil). The applicant demanded the right to an adequate seat, considering his special health situation , which raised public awareness of this disease and may influence future decisions of this court.The Supreme Court of Brazil tended to favour the protection of obese individuals, regardless of the other juridical issues or facts involved in their claims. Obese people were treated as ‘victims’ of an environment and an exclusionary culture that denies them basic rights. Among the 12 cases analyzed, eight (67%) involved positive decisions for obese applicants. Furthermore, three of the four cases with unfavourable decisions were justified only by formal, constitutional and regulation factors, although the discourse that motivated and justified the rulings demonstrates the judges’ deep understanding of a fragility of those affected by the disease.Current research and comprehension of obesity suggests that it has long ceased to be merely a matter of health and now became a major social, economic, juridical, and public policy issue in most countries of the world, especially in those who undertook the ‘nutritional transition’. The alarming growth rate of this epidemic led some western societies to think and conduct researches about the future consequences of obesity in the population. Governments, consumers, and affected populations must understand that their personal action regarding food regulation and health law discussion are essential to ensure that changes towards a healthier environment will occur.In Brazil, the Government works on the opposite way, undertaking a public health policy towards famine called ‘Zero Hunger’ (‘Fome Zero’). This is focused on controlling famine and poverty. However, trends regarding obesity and famine have significantly changed during the last 15 years. Obese people now clearly outnumber by far those suffering from famine in a reversal of the previous trend. We believe it is time for a change in the priorities of the Federal Government of Brazil, considering the increasing obesity epidemic and the sharp decrease in famine in absolute and relative numbers.If the current rate of increase in obesity is maintained, almost the entire population of the United States would be overweight or obese by 2048, reaching one of the most tragic pictures of the human ‘evolution’ and ‘development’.Future generations are about to earn the consequences of inaction while the obesity rate among children and adolescents increases faster than among adults. A political, legal, and social debate is inevitable in countries that face high overweight rates. Some possibilities of solutions have already arisen in different places. One of them is by overtaxing unhealthy foods. Taxing unhealthy foods, particularly sugar-sweetened beverages, could have an important impact on the control of this epidemic. Recent evidence associates high fructose intake levels to a higher risk of the metabolic syndrome, suggesting a pattern towards weight gain. Lowering taxes of healthy products could also be a logical next step.It was also suggested by some landmark centres of research on obesity and health law issues that national governments should lead the effort, just as they did with tobacco control. This initiative achieved success in reducing the number of smokers and the cultural habits that improve the addiction but was preceeded by a major legal suit—the 1998 ‘Tobacco Master Settlement Agreement’, suggesting that a similar deal should be sought regarding obesity control.Another recently-discussed proposal is a better food labelling. This could be an easy, legal and democratic way of helping consumers to make healthier choices. There is some evidence pointing to this pathway.Research on possible public policies targeting obesity started in some countries, universities, and research centres, focusing on better school environments for children and increasing exercise habits, with limited degree of success.This paper addresses decisions made by the superior courts. It could have addressed judicial decisions in all levels of jurisdiction. However, the authors decided to narrow the objectives of the research, willing to illuminate the dominant juridical positions of both countries. The essential legal questions and the major problems tend to reach the superior courts.Obesity is a complex, multifactorial health problem whose analysis certainly involves not only juridical issues but also public health, political and social matters. So, it is probable that this article would not fully reach its purposes of understanding the links and the genesis of the disease, along with its widespread consequences.The analysis of these policies was focused on the social dignity of the subjects, not on decisions regarding funding for medical procedures. This bias could restrain the understanding of the whole public policies towards obesity. This decision aimed to highlight a topic that should be addressed in a better way than actually is. Many medical procedures and their funding already show a degree of organization. Social rights protection still do not have the same standard. The understanding of obesity should consider a wider analysis of its health, legal and social aspects.There are increasing evidences that obesity might not be solved solely through specialized healthcare. This public health challenge requires an intense interdisciplinary debate and a broad social, political and legal response. As a positive sign of slow changes going on, this discussion is leading to the creation of new juridical forums and a huge, varied literature regarding public health, health law, and health courts on the most important universities of the world.


Much debate has arisen from research on muscle synergies with respect to both limb impedance control and energy consumption. Studies of limb impedance control in the context of reaching movements and postural tasks have produced divergent findings, and this study explores whether the use of synergies by the central nervous system (CNS) can resolve these findings and also provide insights on mechanisms of energy consumption. In this study, we phrase these debates at the conceptual level of interactions between neural degrees of freedom and tasks constraints. This allows us to examine the ability of experimentally-observed synergies—correlated muscle activations—to control both energy consumption and the stiffness component of limb endpoint impedance. In our nominal 6-muscle planar arm model, muscle synergies and the desired size, shape, and orientation of endpoint stiffness ellipses, are expressed as linear constraints that define the set of feasible muscle activation patterns. Quadratic programming allows us to predict whether and how energy consumption can be minimized throughout the workspace of the limb given those linear constraints. We show that the presence of synergies drastically decreases the ability of the CNS to vary the properties of the endpoint stiffness and can even preclude the ability to minimize energy. Furthermore, the capacity to minimize energy consumption—when available—can be greatly affected by arm posture. Our computational approach helps reconcile divergent findings and conclusions about task-specific regulation of endpoint stiffness and energy consumption in the context of synergies. But more generally, these results provide further evidence that the benefits and disadvantages of muscle synergies go hand-in-hand with the structure of feasible muscle activation patterns afforded by the mechanics of the limb and task constraints. These insights will help design experiments to elucidate the interplay between synergies and the mechanisms of learning, plasticity, versatility and pathology in neuromuscular systems. The manner in which the nervous system coordinates the multiple muscles in the body is complex. It has been studied for decades, but a more full understanding is needed to enable the development of effective evaluation and treatment methods in disorders that cause neuromuscular disability such as cerebral palsy and stroke. In addition, the computational control of robots has and will continue to improve as the brain’s methods of muscular control are progressively reverse-engineered. Here, we study the capacity of arm muscles to regulate the stiffness of the hand for tasks such as using tools, stabilizing hand-held objects, and using doors. Using a simplified but generalizable model, we show that there will be necessary trade-offs in the functional capabilities of the limb if the nervous system chooses to control muscles in functional groups. This adds to our understanding of the consequences of different strategies to control muscles for real-world tasks with multiple and often competing demands. It enables future research and clinical experiments on the learning and execution of the multiple tasks of varying difficulty encountered in real life. It also sheds light on the design of control strategies for robots to operate in human and unstructured environments. Limb impedance control by the central nervous system (CNS) has been a subject of much study and debate over the past three decades. Numerous experiments and theoretical analyses have studied the biomechanical and neuromuscular capabilities of the CNS to regulate the impedance of a limb e.g., –22). The. The22])The existence and interpretation of muscle synergies is controversial and has received much attention in the recent literature –29. SyneThere is extensive literature on the analysis and synthesis of endpoint stiffness in robotic limbs , 30–33. In this study, we investigate the effects of muscle synergies on endpoint stiffness synthesis and energy consumption . To thisfeasible activation set’ [Importantly, our work takes on the approach that we are interested in finding the families of feasible endpoint stiffness realizations throughout the workspace of the limb. That is, how much can the nervous system control the size, shape  and orientation of endpoint stiffness ellipses for all limb postures? Due to muscle redundancy, there may be multiple ways to achieve any one possible stiffness ellipse. That set of multiple neural commands that can achieve a given realization is its ‘ion set’ , 36. We As mentioned in the Discussion, this neuromechanical approach emphasizes the feasibility of neuromechanical actions and allows us to consider several potential confounds when comparing across studies. Such studies may include examination of the extent, efficacy and nature of training, the influence of limb postures on task goals specified by the experimenter, and the implicit neural strategies specified by the CNS with regard to stiffness regulation in health and disease. Our results also allow us to discuss how learning, experimental design, and neural strategies affect our ability to tune endpoint stiffness.Kend, is a matrix that is calculated as a function of individual musculotendon stiffnesses, which are the elements of the matrix Kmuscles. The individual musculotendon stiffness generated by each muscle is represented by a numerical variable that is, in effect, a lumped parameter model introduced by Hogan and Mussa-Ivaldi [We use a simplified planar arm model with 6 muscles similar to those that have been used in other theoretical and computational studies , 13, 37 a-Ivaldi , 13 that details , 13, 37,Kend) to an ellipse that represents the characteristics of this matrix—shape —measured by the matrix condition number, and orientation of the major axis with respect to the x-axis.We use workspace constraints identical to those used in  to produKend, as a function of muscle active stiffnesses, Kmuscles. As a point of clarification, we focus on muscle active stiffness that results from the feedforward activation of the muscle such as during force production or co-contraction. We do not include passive stiffness, which normally refers to the inherent material properties of the limb or muscles with no muscle activation. This could arise, for example, from tendon properties. Similarly, as mentioned in the Discussion, we do not include the time-delayed stiffness resulting from reflexes, often called reflexive stiffness. In our formulation, Kend relates the vector of differential endpoint displacements to differential endpoint forces:Kjoint, relates the vector of differential joint angle displacements to differential joint torques:J . As we will see in the results, this one-dimensional manifold in muscle activation space does not allow the realization of the arbitrary endpoint stiffness ellipses because the synergies, by coupling muscles, also couple two important stiffness characteristics: the stiffness ellipse’s shape and orientation. That is, in the presence of synergies, as just described, there is only one free parameter that can be varied to control these characteristics, aelbow/ashoulder. Therefore, changing orientation independently of shape is impossible.In the presence of these synergies, one parameter suffices to change the orientation and shape of the endpoint stiffness ellipse: the ratio of elbow synergy activation to shoulder synergy activation, aelbow/ashoulder) over a range of 2 orders of magnitude (1/10 to 10) to see how much the orientation of the ellipse is able to change.To further explore this coupling of task constraints by synergies, we vary the ratio of shoulder synergy activation to elbow synergy activation and the endpoint stiffness has a given desired shape and orientation, as in In the absence of synergies in our model , we can determine if the arm is able to meet the constraints thatThen if the feasible activation set begins as a 3-dimensional unit cube in the positive octant.The constraint of zero endpoint force is a 2-dimensional plane in activation space passing through the origin. This is because endpoint forces have a minimal value of 0 at zero activation).The constraint for desired endpoint stiffness of unity is also a 2-dimensional plane in activation space, but it does not pass through the origin. This is because muscle activation is required to produce stiffness: at the origin, there is no muscle contraction, therefore there is no muscle stiffness stiffness or endpoint stiffness.An illustration of these constraints, the existence of a solution, and the potential for energy minimization in the absence of synergies is illustrated in a1 = 2a2) results in an additional constraint plane that passes though the origin that will reduce the feasible activation set, reducing the dimensionality of the solution space. In this simple example, the dimensionality is reduced to zero—a unique solution [This geometric interpretation , 43, 44 solution , 43, 45.solution , synergiIn our 6-muscle model, the activation hypercube is 6-dimensional. The constraint of zero endpoint force is a 4-dimensional hyperplane in activation space passing through the origin  is realizable. We did this every 5° around the full range of orientations  and then checked the fraction of these orientations that are realizable. An example of the fraction of realizable orientations for all postures in the workspace is shown in The constraints in the realizability tests have five equality constraints Eqs  and 13. Our rationale for quantifying these ratios is that, for given observed stiffness ellipsoid in human subjects experiments, we want to know whether or not the central nervous system could minimize energy expenditure. If there is a large possible range of energies expended for a same endpoint stiffness ellipse, then it may only be possible for experimental means such as EMG to reach strong conclusions about energy minimization. But if the range is low, then EMG measurements may not have the resolution to reveal much additional information about energy expenditure (above the information obtained by only measuring the stiffness ellipse).−1 to 10. The arm endpoint is in a sample x − y position , where each link of the arm has length of 1. The area of the ellipses in To explore the effect of synergies in detail, we performed a more detailed analysis for a single posture. In that sample posture, The range of orientations is approximately 70°, which represents a realizable fraction of orientations of about 0.39. In this posture, shown in any orientation. Note the strong dependence on the posture of the arm . In general, the maximal possible energy reduction for many of the workspace postures for these stiffness ellipse shapes is low (10–30%), but can increase significantly to around 50% for some specific postures.The literature on muscle synergies is large and growing. There are already several papers debating their origins, advantages, and disadvantages , 42, 46.In the literature mentioned above, the origins of synergies as well as their specific structure and permanence continue to be debated. In their paper on static arm postures, Osu and Gomi (1999) mention that other arm synergies have been reported and that the regulation of muscle activation in static conditions seems to be quite different from that during movements. Nevertheless, this does not affect our main finding that synergies—regardless of their origin, structure or permanence—have important neuromechanical consequences in a variety of functional domains. This is because synergies imply a loss of control degrees of freedom . Therefore, the specifics of the synergies we chose to simulate as reported by Osu and Gomi do not affect the generality of our results. In fact, we went on to simulate five additional synergies as shown in Figs It is important to mention that comparing muscle coordination and stiffness regulation in static versus dynamic movement conditions may not be advisable—or even possible. This stems from the fact that the physics and neuromuscular physiology of the control of static force versus movement are inherently distinct and can even be incompatible; see , 48–50 aThe feasible activation set—i.e., all feasible neural commands to achieve a given task , 43, 44—This geometric approach uses a 6-muscle arm model with experimentally derived synergies to show that synergies severely constrain the ability to control the properties of the stiffness of the arm’s endpoint. Furthermore, it also shows reduction in the flexibility of energy consumption to implement them. That is, by reducing the dimensionality of the feasible activation set, synergies drastically limit the ability to orient the endpoint stiffness ellipse independently of its shape. The range of achievable orientations in the absence of synergies is already very sensitive to posture, but still allows significant energy minimization in some postures. Implementing synergies drastically reduces, and can even remove, the ability to minimize energy.Ks is the shoulder stiffness provided by co-contraction of the mono-articular shoulder muscles, Kb is the bi-articular joint stiffness provided by co-contraction of bi-articular muscles, and Ke is the elbow stiffness provided by co-contraction of mono-articular elbow muscles. This implies 3 constraints, and therefore 3 degrees of freedom for the system. However, our formulation without synergies has 4 degrees of freedom since only 2 constraints must be satisfied  of the endpoint of a simulated arm can be controlled in the presence or absence of muscle synergies. That is, the extent to which the endpoint of the limb would displace passively in response to a force perturbation in every direction. That stiffness is the product of the level of activation of each muscle, and the anatomy and posture of the limb. We assumed, as others have in the past, that the active stiffness of a muscle is linear and proportional to the maximal force a muscle can produce and the level to which it is activated. While the linearity of active muscle stiffness with respect to muscle strength and activation is likely not entirely realistic, we focused on the effects of the presence or absence of muscle synergies. Using a nonlinear relationship would likely produce different numerical results for the precise shape, size and orientation of stiffness ellipses. However, it would not overcome the limitations that muscle synergies impose because those limitations come about from a reduction of the number of individually controllable muscles. That is a matter of scale rather than quality. Future work should naturally explore whether or not more realistic physiological mechanisms for muscle stiffness exacerbate the effects of synergies—particularly in neurological conditions. In addition, this model is limited in that it does not take into account passive muscle stiffness, reflexive stiffness, or feedback pathways, which can clearly be used to minimize energy further depending on the frequency content of a perturbation or motor noise during a task. It has been suggested  that somA subtle but important issue is that studying symmetric endpoint stiffness does not take away from our findings, bur rather enhances our result about the functional limitations of synergies. Adding a net endpoint force (or torque) deforms the symmetry of endpoint stiffness, but it also further constrains the range of stiffness modulation. Balasubramanian and colleagues have made this point well by indicating that defining an endpoint force imposes an additional set of functional constraints that compromise the modulation of endpoint stiffness . SimilarOur model, like many others used to study arm stiffness , 13, 37,Our results suggest ways in which future high-dimensional models and arm stiffness experiments may be conducted to analyze stiffness synthesis strategies used by the CNS such as synergies, energy minimization, posture adjustment, and active reflex pathways. Reaching experiments could test stiffness ellipses in various postures during the reaching movement, since stiffness ellipsoid orientation flexibility is very sensitive to small changes in posture. Findings that conflict with the results of such a study could be analyzed in more detail as this would suggest significant feedback pathways that were developed as a result of motor learning and neural plasticity. More research into muscle synergies will help elucidate existing mysteries of neuromuscular control and empower improved mechanisms for therapeutic interventions for neuromuscular disorders in aging and disease.More generally, to our knowledge, this is the first study of the neuromechanical and energetic consequences of using synergies while meeting the multiple and compounding force and stiffness constraints that define tasks in the real world, particularly important for unstructured environments. As pointed out previously e.g., , 45, 47), 4745, 4An objection to the strength (though not to the substance) of this conclusion is that having many more muscles will naturally allow the implementation of synergies without such a drastic reduction of the feasible activation set. We agree with this interpretation as we have argued that thinking of vertebrates as having ‘too many’ muscles is paradoxical with evolutionary biology and clinical reality. That is, we have barely enough muscles for versatile and robust function in the real world , 45, 47.Set the necessary endpoint stiffness size, shape and orientation Specify the direction, speed and duration of the movement Control for the desired endpoint forces and torques Consider the influence of motor noise α-motoneuron pools to produce the necessary joint torques as per the classical muscle redundancy force-sharing problem α-motoneuα-motoneuron pools across shortening and lengthening muscles [Coordinate reciprocal inhibition of  muscles γ-drive and/or inhibit the stretch reflex in muscles undergoing eccentric contractions γ-drive aMediate interneuronal interactions Satisfy the temporal constraints of conduction velocities, muscle excitation-contraction dynamics, and activation/deactivation time constants  to ensurMore generally, every modeling study must assess its generalizability to everyday life—especially models with a relatively small number of joints and muscles. In such simplified systems, a few constraints may suffice to artificially deplete the system of its control degrees of freedom. The question then becomes whether, in models with many more muscles, the achievable stiffnesses are ‘good enough’ for the usual, day-to-day operation of the limb; and if so, from the functional perspective this reduced flexibility may not really be a disadvantage at all. We and others have debated this important issue in the contexts of muscle redundancy for the production of static forces, unimpeded limb motion, and their combinations , 54, 55.This compounding of multiple, potential conflicting, spatial and temporal constraints naturally leads to a dramatic shrinking of the set of feasible neural commands for natural movements even when we have many muscles. This line of thinking helps clarify the apparent and longstanding paradox between the classical concept of muscle redundancy and the clinical reality of motor development and dysfunction . For exaIn spite of the simplified model used in the prior literature and here, our results nevertheless add to current thinking about endpoint stiffness in two critical ways. First, they enable us to explore the specific task-level trade-offs associated with specific synergies. And second, they show that there is a natural limit to how generalizable and flexible any synergy can be. Simply said, every synergy that is prescribed will reduce the feasible activation set (and thus the set of feasible actions) as strictly as the mechanics of the limb or the constraints of the task.Thus if one is to prescribe synergies to meet the multiple constraints of the many tasks we face in real life, how many synergies should one learn? The idea that each prescribed synergy solves, by construction, a well-defined control problem is well studied in the control literature , 65, 66.S1 Dataset(XLSX)Click here for additional data file.


Lack of appropriate human resources planning is an important factor in the inefficient use of the public health facilities. Workforce projections can be improved by using objective methods of staffing needs based on the workload and actual work undertaken by workers, a guideline developed by Peter J. Shipp in collaboration with WHO—Workload Indicators of Staffing Need (WISN). A cross-sectional study was carried out to estimate the nursing stuff requirement for the rural hospitals and provide a quantitative description of imbalances, if there is any, in the allocation at the district level during 2011. The average WISN turns out to be 0.35 for entire district, which means only 35% of the required nurses is available or 65% understaffed. So, there is an urgent need for more allocations and deployment of staff so that workload can be tackled and evenly distributed among all nursing personnel. Continuing and worsening shortages of nurse nationally and internationally have been a matter of concern . ShortagPresently, policy-makers in India are concerned about both efficiency and equity in the use of resources in the health sector. In the task of making estimation for the existing and projected manpower needs in the health sector, there are a number of problems, such as (a) highly-inadequate information system in health; (b) lack or laxity in registration systems and current stock; (c) inadequate information on supply; (d) lack of information on migration, death rates, and attrition on other grounds; and (e) methodological problems relating to estimation of manpower requirements . EffortsPeter J. Shipp, in collaboration with WHO, Geneva, has developed guidelines to determine Workload Indicators of Staffing Need (WISN) . The WISA descriptive cross-sectional study was carried out during April 2012 to March 2013 in Burdwan district in the state of West Bengal, India. Burdwan, a district of West Bengal (an eastern state of the country), with a population of 7,717,563 is the most densely-populated district   from specific health staff category .The basis of the WISN Method is activity standard, which is the time it would take for a well-trained and well-motivated member of a particular staff category to perform an activity at acceptable professional standards. In this study, the nursing personnel with substantial experience in their field having thorough knowledge about the nursing practice and administrative issues were interviewed to identify different activities and set working time for each component. There were, sometimes, differences in opinion regarding time requirement; in such situation consensus were reached taking average of opinions of three experts. According to Peter J. Shipp, the author of the original WISN manual, experts are “expected to bring to bear professional expertise and recent working experience.” We also found it difficult to group different activities for setting activity standard as there were a lot of subtasks in each of the components of activity.Available working time and the actual time spent per staff category at work were calculated giving due consideration to all the official leaves. The available working time was obtained by subtracting the duration of total absence from the total available working days in a year. Out of 52 weeks per year, 17 weeks are unavailable as working weeks, and the remaining 35 weeks are available as working time, which is 210 days or 1,680 hours per year. Government offices in Burdwan remain open for 8 hours on six working days in the entire year .Hospital statistics regarding different patient-care activities for all rural hospitals of Burdwan district is also given . The actFor analysis, the staff members who were directly involved in different nursing care in hospital were considered; sister-in-charge was excluded from calculation. Rural hospital in Memari had maximum requirement of 32, in addition to the existing nursing staff working to bear the workload as shown by the last year's statistics and least requirement of 10 nurses shown by rural hospital in Ballavpur. Rural hospitals in Singhat, Srirampur, and Manker showed maximum workload pressure ranging from 70% to 75%. The WISN ratio for rural hospital in Manker turned out to be 0.30; for rural hospital in Singhat, it was only 0.25. It means there were only 25% staff members available as per their need; there was 75% deficit or 75% overburden .As in many other developing countries, the Ministry of Health in India is constantly under pressure to provide better health services to an ever-increasing population and to maintain equity in the distribution of those services but resources are not keeping pace with the increase in demand. Thus, health administrators must make all efforts to achieve optimum utilization of resources, particularly human resources, in order to have greater impact (by improving current effectiveness levels) and equity in the provision of health services  and economy of operation . Population ratios and standard staffing schedules are generally used in determining the workforce requirements. These methods have serious limitations. Population ratios are based on all qualified staff in a particular category, irrespective of their specialty. On the other hand, with the standard staffing schedules, the distribution of the facilities themselves is a major factor determining staffing needs. None of these methods takes account of the wide local variations with respect to morbidity, access to facilities, etc. Staffing norms based on population ratios and standard staffing schedules are usually set somewhere in the middle of the range. This leads to overstaffing in some facilities and understaffing in others. The latter facilities, unable to cope with their workloads, apply for more staff and frequently get an increase because the request is, in fact, justified. Once this precedent has been established, other facilities also seek staff increases even though their staffing levels are in fact adequate for their workloads. Thus, the authority of the norms or standard staffing schedules disappears and their value in the management and control of human resources for health (HRH) is diminished. Using the WISN Method for human resource management in a district, by comparing the estimated results (ratios and differences) for a group of facilities, a manager can identify whether there are any staffing inequities between the facilities and, moreover, what can be done to improve the situation.et al. ; information on these was prospectively collected for the purpose of the study.As all the rural hospitals of one district was chosen, the demographic situation and morbidity and mortality status, on one hand, and requirement of healthcare beneficiaries, on the other, are more or less similar everywhere; so, there was less chance of differences in services offered in the hospitals depending on local population health conditions or the types of medicine or surgery practised by the doctors or the physical facilities, availability of supplies, etc., which might create barriers to more efficient work.This study was carried out among only one category of health personnel working in the facility. Precise estimation in the process of setting activity standard was not possible for all activities as there was possibility of sharing the activity by other category of workers as and when required. Moreover, estimation of activity standard may be affected by subjective method of setting the standard. The WISN Method overlooks the consequences of ‘errors’ arising from the invalid assumptions. The estimation by this method is based on current utilization rate of service and does not consider the possible increase in utilization rate in future.The health sector of India is constantly under pressure to increase efficiency and equity. Appropriate human resources management and planning can contribute greatly to the improvement of efficiency and equity in the health sector. Presently, no objective criterion is followed in India in determining staffing needs as well as in allocating workforces. Deployment, transfer, posting, etc. are important issues for human resources management in the health sector. Workload indicator of staffing need (WISN) has been estimated for nurses working in different rural hospitals under Burdwan district of West Bengal. The average estimate of WISN turned out to be 0.35. However, there exists a wide variation of this figure among the rural hospital. It varies from 0.25 to 0.58. The presence of significant variation of WISN indicates that health managers have a role in increasing efficiency and equity by making optimal deployment of workforces among facilities. In a nutshell, planning for nursing personnel in Burdwan district can be done by using WISN Method for proper allocation and deployment so that workload can be evenly distributed among nursing staff in all hospitals to improve the healthcare services in rural hospitals.The study was partially self-funded and partially funded by Indian Association of Preventive and Social Medicine , India, under grant for best research project proposal initiated by Prof. Akalanka Bhandari in 2012.Conflict of interest: The authors declare no conflict of interest.


Social media analysis has rarely been applied to the study of specific questions in outcomes research.The aim was to test the applicability of social media analysis to outcomes research using automated listening combined with filtering and analysis of data by specialists. After validation, the process was applied to the study of patterns of treatment switching in multiple sclerosis (MS).A comprehensive listening and analysis process was developed that blended automated listening with filtering and analysis of data by life sciences-qualified analysts and physicians. The population was patients with MS from the United States. Data sources were Facebook, Twitter, blogs, and online forums. Sources were searched for mention of specific oral, injectable, and intravenous (IV) infusion treatments. The representativeness of the social media population was validated by comparison with community survey data and with data from three large US administrative claims databases: MarketScan, PharMetrics Plus, and Department of Defense.A total of 10,260 data points were sampled for manual review: 3025 from Twitter, 3771 from Facebook, 2773 from Internet forums, and 691 from blogs. The demographics of the social media population were similar to those reported from community surveys and claims databases. Mean age was 39 (SD 11) years and 14.56% (326/2239) of the population was older than 50 years. Women, patients aged 30 to 49 years, and those diagnosed for more than 10 years were represented by more data points than other patients were. Women also accounted for a large majority  of reported switches. Two-fifths of switching patients had lived with their disease for more than 10 years since diagnosis. Most reported switches  were from injectable to oral drugs with switches from IV therapies to orals the second largest switch . Switches to oral drugs accounted for more than 80% (927/1114) of the switches away from injectable therapies. Four reasons accounted for more than 90% of all switches: severe side effects, lack of efficacy, physicians’ advice, and greater ease of use. Side effects were the main reason for switches to oral or to injectable therapies and search for greater efficacy was the most important factor in switches to IV therapies. Cost of medication was the reason for switching in less than 0.5% of patients.Social intelligence can be applied to outcomes research with power to analyze MS patients’ personal experiences of treatments and to chart the most common reasons for switching between therapies. The Internet is rapidly becoming the first source of general and specific information on illnesses and treatments for a large number of people worldwide. Surveys have reported that between 70% and 75% of online users in the United States and Europe search for health care information -4. SociaFor researchers, this explosion of online activity has generated a treasure trove of digital data that can be mined for insights into various aspects of health-seeking behavior and treatments. In the areas of infectious disease and public health, social network messages have been analyzed  -9. SociaIn recognition of this value of the Internet and digital media, the European Medicines Agency in its guideline on good pharmacovigilance practices recommends that marketing authorization holders should regularly screen Internet or digital media  under their management or responsibility for potential reports of suspected adverse reactions .Despite this intense activity, social media analysis has rarely been applied to the study of specific questions in outcomes research. To test the validity of social media information and the applicability of social intelligence to outcomes research, we developed a comprehensive process that blends automated listening with the filtering and analysis of data by life sciences-qualified analysts and physicians. The process was designed to combine the advantages of purely manual and purely automated analyses. Manual coding in content analysis studies is superior to automatic content analysis in capturing complex semantic relationships between concepts or recognizing irony or sarcasm, which are frequently used in the informal conversation typical of social media. Automated analysis systems are superior in their sheer computing power, required to scan large datasets for relevant lexical entities, coding, and statistical analysis.The mix of manual and automatic content analysis has been applied in other settings , but to In this pilot study, we validated our social intelligence process by analyzing the representativeness of the social media population with multiple sclerosis (MS). To apply the analysis to outcomes research, we then used the collected data to study patterns of treatment switching to and from oral therapies in the MS population.Social intelligence analysis combines automated listening to social media conversations with the filtering and analysis of data by human experts. As such, it is a noninterventional, retrospective database analysis of data available in the public domain.The population was patients with MS from the United States. Patients who did not mention their location country or mentioned their location as not in the United States were excluded from the switchover analysis. Data sources for user-generated content were Facebook, Twitter, blogs, and online forums. The sites were selected because they are highly active, with a large number of users, and the content is publicly available and not redacted. Only publicly available social media conversations were included in the listening process and no password-restricted information was accessed. No patient-identifiable information available on social media was collected. Age, sex, and geographic location of social media users were collected when available.The overall process is illustrated in The identification of potential switches was performed by the automatic system based on a set of predefined categories: potential switches; category of conversations as information sharing or information seeking; themes of conversation as cost, efficacy, side effects, or adherence; and conversation sentiment as positive or negative. For potential switches, the system was trained to recognize conversations containing switching patterns, terms, brands involved in a switch, and the potential reason for the switch. The data were filtered for relevance to the study objectives. The identification and grouping of content was done by the automated system. The automatic identification was followed by manual analysis of the complete set of records to eliminate errors and record the involved brands and reasons for switchovers.The objectives of the analysis were (1) to explore the feasibility of using social media analysis to address outcomes questions in health care that focus on a population of MS patients; (2) to validate the representativeness of the social media population by comparing the characteristics of the database population with data on MS patients obtained by other methods, such as medical records, patient advocacy groups, or general practitioners; and (3) to use the validated database to analyze switching patterns and reasons for switching between oral and injectable classes of MS therapies.This study was designed, implemented, and reported in accordance with the Guidelines for Good Pharmacoepidemiology Practices of the International Society for Pharmacoepidemiology , the StrThe information extracted by the automated system was organized by social platform . The data were further stratified monthly for each platform. To generate representative samples for the population dataset for manual review, random samples were extracted for each month and for each platform based on a 95% confidence interval with a 5% margin of error. These data were subjected to manual analysis by life sciences-qualified analysts, who were guided by a physician, to confirm the representativeness of the samples. After the review of these samples, validation sample sets were generated for three random months for each platform using the preceding methodology to cross-validate the findings derived from the sample set.Social media conversations were monitored between October 1, 2013 and October 31, 2014. A total of 49 forums and 152 blogs were used for the analysis. All publicly available Facebook pages were searched for the relevant semantic information. The automated system extracted 25,073 social media data points (unique posts on any specific media platform) in this time period. A total of 22,887 relevant data points were identified: 8672 from Twitter, 6919 from Facebook, 6505 from Internet forums, and 791 from blogs. Of these, 10,260 data points were sampled by the analysts for a detailed manual review: 3025 from Twitter, 3771 from Facebook, 2773 from Internet forums, and 691 from blogs.The demographics of the population are shown in As a validation of the representativeness of the social media population, the characteristics were compared with those from a survey in three US communities in Texas, Ohio, and Missouri . As showA total of 1684 data points were identified as treatment switches. Switches were most frequent among patients on injectable therapies who were represented by 1114 of 1684 (66.15%) data points for switches . The larRelative rates of switches away from oral, injectable, and IV therapies, respectively, are shown in By monitoring conversations, it was possible to identify a number of reasons for drug switching discussed among patients. Four reasons accounted for more than 90% (1130/1234) of all switches: severe side effects, lack of efficacy, physicians’ advice, and greater ease of use . The thrThe results from this pilot study indicate that social intelligence can be applied to outcomes research with the power to tease out facts not available by other analyses, such as retrospective analyses of claims databases, commonly employed in outcomes research. Using a combination of automated listening and filtering and analysis of data by life sciences-qualified analysts and physicians, it was possible to obtain data on MS patients’ personal experiences of their treatments and to generate a map of the most common reasons for switching between therapies.The study had three objectives. The first was to test the applicability of social intelligence in outcomes research. Use of the Internet for medical information varies with the condition: patients with MS have among the highest rates of use at 60% to 80% of (US) patients compared with 35% of (Canadian) patients with spinal cord injury ,19. In aAlthough published data are likely to lag behind the rapid increase in Internet use fed by the mobile revolution, choosing MS as the condition for our analysis was expected to provide a large dataset to analyze which could be assumed to represent a varied population and reduce the potential for bias. The large number of data points related to MS included in our sample shows that there is an extensive and active social media population generating sufficiently large datasets with relevant information to enable analysis of questions typically posed in outcomes research.The second objective of the study was to validate the representativeness of the social media population for MS. A comparison of the characteristics of the social media population with other MS patient cohorts characterized in community surveys or by analysis of large US administrative claims databases showed strong similarities between populations identified with different methods. Likewise, the analysis of switching patterns yielded similar results to those from other sources: market analyses by Novartis (data on file) indicate that most switches in real life are from injectable to oral therapies, including a not negligible percentage of patients on IV drugs. The similarities between these results from different sources indicate that the risk of bias in online data is no greater than that in acceptable and validated analyses of clinical reality in populations identified and characterized using other methods.Most patients in the social media population had been living with their disease for several years and the age distribution corresponds to the means for MS patients on therapies. That a large majority of the population were women is a reflection of the demographics of the MS population because the disease is several times more prevalent in women . Our ratThe third objective was to apply the social intelligence approach to the study of patterns of treatment switching between oral, injectable, and IV therapies for MS. For the purpose of the analysis, oral therapies were represented by the drugs Tecfidera, Gilenya, and Aubagio. In the time period covered by the data, these three compounds represented all available oral medications on the US market. Because the treatments represent different molecular entities, there is a reduced risk of potential bias from social media discussions of drug-specific characteristics not directly related to the oral or injectable nature of the different treatments. Injectable drugs were represented by five common BRACE therapies that together cover the majority of injectable MS medications in the United States. This pilot analysis did not attempt to tease out drug-specific reasons for switching, although the performance of the analysis indicates that such an exercise would be possible with the methods employed in this analysis.There are few published data on patients’ reasons for switching between MS therapies. Most investigators have focused on efficacy comparisons in patients switching from one treatment to another, using observational data from registries to approach the real-world situation . Our finThe strength of the method lies in the combination of automated and manual analysis. Manual analysis alone is too labor-intensive to be feasible in social media analysis of large datasets. Automated tools for content analysis will not capture the varieties of human expression, such as irony or the use of nonstandard abbreviations, nor will they identify complex semantic relationships between concepts or process information expressed in colloquial language typical of social media ,27. The The study has a number of limitations. First, all social media are susceptible to misinformation , which may be difficult to identify even for the human analysts and guiding physicians . There iAlthough these limitations should be acknowledged, our analysis shows that when applied to appropriate questions that are frequently discussed openly by patients, social intelligence can be a powerful tool for outcomes research, providing information on specific factors driving patient’s health-seeking behavior that may not be obtainable by other means.