Millions of patients require implantable cardiac devices for management of cardiac dysrhythmias. These devices are susceptible to erosion, exposure, or infection and plastic surgeons are consulted when salvage is required. As of yet, an anterior muscle-splitting approach to effectively and safely relocate the device into the subpectoral position has not been described in the plastic surgery literature. The authors retrospectively reviewed the charts of 7 patients who required repositioning of cardiac devices. Indications for repositioning included exposure, erosion, infection, hematoma at the time of primary placement (3), and one cosmetic revision. All patients were treated with subpectoral repositioning of the device into the subpectoral space via an anterior muscle-splitting approach. Six of 7 patients (86%) achieved successful long-term repositioning in the subpectoral position without recurrent exposure or hematoma and with good cosmetic results. One patient who had a prior history of multiple failed device placements required reoperation due to recurrent infection. The anterior muscle-splitting technique proposed by the authors for defibrillator or pacemaker salvage is a feasible technique with promising results. Plastic surgeons should be aware of this simple and effective approach. In particular, the evolving design of implantable cardiac devices such as pacemakers and automatic internal cardiac defibrillators has improved the management of patients prone to debilitating dysrhythmias. Every year, nearly 300 000 new patients in the United States require implantable cardiac devices.2Traditionally, cardiac electrophysiologists perform primary implantation of these devices. These practitioners tend to favor a subcutaneous site of implantation in the chest that obviates dissection of deeper tissues. While this approach is well tolerated by most patients and the subcutaneous space is conveniently accessible to the implanting electrophysiologist, it is not appropriate for all patients. For example, in patients who are cachectic, primary device placement into the subcutaneous space of the infraclavicular chest can lead to a visible deformity that may be unacceptable or intolerable Fig .,11In the case of device infection, pain, palpability, or exposure Fig , plastic9While other methods for in situ salvage exist, the authors implement a method of salvage that maintains the original access incision while safely placing the salvaged device and/or leads into a fresh and well-vascularized tissue plane. Specifically, this technique relocates the device beneath the pectoralis major muscle via an anterior muscle-splitting approach.The authors retrospectively reviewed the charts of 7 patients who presented with impending or frank exposure, infection, cosmetic concerns, or hematoma at the time of primary placement by cardiology. All patients were treated with subpectoral repositioning via a muscle-splitting approach. The patients were treated over a 36-month period between August 2008 and August 2011 . The institutional review board approved this study.Patients underwent salvage surgeries under sterile technique with intravenous (IV) sedation and local anesthesia in the electrophysiology cardiology laboratory. Initial debridement of the pocket involved resection of necrotic skin and subcutaneous tissue overlying the old generator, and evacuation of any hematoma or periprosthetic infection, abscesses, or purulence. The surgical team then externalized and disconnected the devices from indwelling AV leads and performed a partial or total capsulectomy. The capsulectomy required meticulous dissection to skeletonize the leads, especially as they approach their entry into the subclavian system. After capsulectomy, the resulting pocket was copiously irrigated with antibiotic solution and inspected for hemostasis. Dissection was carried to the base of the pocket where the fascia of the pectoralis major muscle was encountered and the muscle was incised in the orientation of its fibers. A muscle-splitting approach was employed to divide the pectoralis major muscle and identify the subpectoral space. Once identified, a pocket was developed subpectorally using a combination of blunt dissection and electrocautery. At the base of the pocket, the pectoralis minor muscle was left unperturbed. For medial pockets or dissections, particular care was exercised to avoid disruption of neighboring perforators of the underlying internal mammary artery and vein. Throughout the process, awareness and preservation of the cephalic vein and identification of the pectoral branch of the thoracoacromial trunk are paramount. Once a satisfactory subpectoral pocket was created, a new cardiac electrical generator unit was placed and connected to the preexisting AV lead system Fig . Next, tEnterobacter cloacae. Because of the recurrent history of infection with device placement in the chest wall, the authors chose to place a new device and lead system in the abdominal subcutaneous tissue of the right lower quadrant. The patient was successfully treated with IV antibiotics and did not develop subsequent infection.Between July 2008 and August 2011, a total of 7 patients were treated. There were 5 women and 2 men with a mean age of 59 years . In all cases, muscle-splitting technique was performed without intraoperative complications. The mean follow-up was 21 months . Indications for subpectoral repositioning of the cardiac device included impending exposure (1), erosion (1), infection (1), hematoma at the time of initial placement by primary service (3), and cosmesis (1). Six patients (86%) achieved long-term successful repositioning of the generator in the subpectoral position with no recurrent infection or exposure, and with good cosmetic results. Only 1 patient had a failure of treatment due to a recurrent open wound and wire exposure 2 months postoperatively. In this case, failure was attributed to a 14-year-old lead that was not exchanged at the time of device salvage. This patient had a history of several failed device placement in bilateral subcutaneous locations secondary to infection requiring replantation by the cardiac electrophysiology service. After the authors salvaged the device with subpectoral repositioning, recurrent infection developed with a positive wound culture for lateral approach have been described.Subpectoral positioning of cardiac devices is not a novel concept. In fact, techniques for subpectoral positioning of cardiac devices using a There is a paucity of literature on the management of infected devices or devices that are exposed because of either erosion through the overlying skin or secondary to poor wound healing. Device explantation is often not feasible because of risks including sudden cardiac death. For this reason, salvage by repositioning of these infected or exposed cardiac devices often becomes imperative in managing patients with debilitating cardiac arrhythmias.-Less data has been published on techniques used for device salvage in the setting of infection or device erosion. Several authors have independently reported successful outcomes with treated infected device pockets. Taylor and colleagues15Another group, Kolker et al,As mentioned previously, subpectoral positioning for device salvage has been described. In 1995, Foster,26Most recently in 2010, Al-Bataineh et al25Our series demonstrates comparable overall success with true subpectoral positioning of implantable cardiac devices. Analysis of our 7 cases, with indications related to impending or frank exposure, infection, hematoma, and cosmesis, revealed an 86% success rate with subpectoral repositioning with 21-month mean follow-up.Important advantages of the anterior muscle-splitting technique include the ability to reposition the device into a clean plane, coverage with healthy vascularized muscle, and that even with debridement of necrotic skin and subcutaneous tissue, skin of the original pocket is easily closable over drains by means of simple undermining without the need for local flaps. The results demonstrated no hematoma or pneumothoraces, and nipple sensation is not at risk with this approach. All surgeries were performed safely under IV sedation with local anesthesia in the electrophysiology laboratory allowing for easy access to fluoroscopy and interrogation software. This facilitated a collaborative approach between cardiology and plastic surgery allowing for device exchange and subpectoral placement simultaneously in the electrophysiology laboratory.Like previous reports of secondary repositioning of cardiac devices into the subpectoral position, our series is retrospective and our sample size is low. Therefore, it is difficult to draw stringent conclusions. Our results match existing data outcomes and demonstrate a safe approach to the subpectoral space with minimal morbidity.As in the treatment of any infected prosthesis, if explantation of an infected device is not possible, then aggressive debridement, obliteration of all dead space, and coverage with healthy vascularized tissue such as muscle flaps are essential principles of management. There is a wide spectrum of treatment options (see Table


Colorectal cancer is the second most common tumor in developed countries, with a lifetime prevalence of 5%. About one third of these tumors are located in the rectum. Surgery in terms of low anterior resection with mesorectal excision is the central element in the treatment of rectal cancer being the only option for definite cure. Creating a protective diverting stoma prevents complications like anastomotic failure and meanwhile is the standard procedure. Bowel obstruction is one of the main and the clinically and economically most relevant complication following closure of loop ileostomy. The best surgical technique for closure of loop ileostomy has not been defined yet.A study protocol was developed on the basis of the only randomized controlled mono-center trial to solve clinical equipoise concerning the optimal surgical technique for closure of loop ileostomy after low anterior resection due to rectal cancer.The HASTA trial is a multi-center pragmatic randomized controlled surgical trial with two parallel groups to compare hand-suture versus stapling for closure of loop ileostomy. It will include 334 randomized patients undergoing closure of loop ileostomy after low anterior resection with protective ileostomy due to rectal cancer in approximately 20 centers consisting of German hospitals of all level of health care. The primary endpoint is the rate of bowel obstruction within 30 days after ileostomy closure. In addition, a set of surgical and general variables including quality of life will be analyzed with a follow-up of 12 months. An investigators meeting with a practical session will help to minimize performance bias and enforce protocol adherence. Centers are monitored centrally as well as on-site before and during recruitment phase to assure inclusion, treatment and follow up according to the protocol.Aim of the HASTA trial is to evaluate the efficacy of hand-suture versus stapling for closure of loop ileostomy in patients with rectal cancer.DRKS00000040German Clinical Trial Register Number:  Colorectal cancer is the second most common tumor in developed countries, with a lifetime prevalence of 5% ,2. ApproOne randomized controlled trial (RCT) including 141 patients over 6 years has compared hand-sutured and stapled anastomosis for closure of loop ileostomy so far . The resHA/pHA denotes the rate of occurrence of bowel obstruction within one month after ileostomy closure in the hand-suture group (HA)/stapler group (STA), then the following two-sided test problem is assessed: H0: pHA = pSTA vs. H1: pHA ≠ pSTA.The objective of the HASTA-Trial is to investigate whether there is a difference in rate of bowel obstruction one month after hand-suture as compared to stapling loop ileostomy closure. If pPatients with history of low anterior resection (LAR) and creating of a protective loop ileostomy for rectal cancer who are planned for elective closure of loop ileostomy will be recruited for this trial.The HASTA-Trial is conducted by a national study group consisting of certified bowel centers and other German hospitals of all level of health care. Trial design and management are under the responsibility of the Study Center of the German Surgical Society, biostatistical planning, data management and analysis is performed by the Institute of Medical Biometry and Informatics, University of Heidelberg.• Patients equal or older than 18 years scheduled for elective ileostomy closure after LAR• Informed consent• Pathologic findings in routine preoperative diagnostic tests (e.g. anastomotic leakage) which do not allow a safe ileostomy closure• Participation in another intervention-trial with interference of intervention and outcome of this study• Expected lack of complianceCenters are asked to document potential patients in a screening log. Thus, reasons for exclusion are documented.The prior assumptions for sample size calculation are based on the results of Hasegawa et al. (2000)  and asshttp://www.randomizer.at). This software allows choosing different randomization methods as well as different sets of parameters for the chosen method.The randomization numbers will be allocated to the two groups in balanced permuted blocks and stratified by center using the web-based software "Randomizer" provided by the Institute of Medical Informatics, Statistics and Documentation of the Medical University of Graz  is brought into the two opened antimesenteric apexes of the intestinal shanks to facilitate side-to-side  anastomosis Figure . The apeAfter thorough mobilisation the loop ileostomy is resected using two bowel clamps. An end-to-end anastomosis is performed as follows: a two-layer continuous suture using four Polydioxanon equivalent sutures (USP 5-0). The inner layer consists of a transmural suture, the outer layer of a sero-muscular suture. Alternatively, interrupted sutures may be performed depending on local standards. The abdominal wall and the skin are closed in the same way as for stapled closure.No other method of ileostomy than the randomized and described technique in the protocol should be used for anastomosis. Any protocol violation has to be reported with a clear description.The postoperative care is performed according to the principles and standard of the department.The primary endpoint is the occurrence of bowel obstruction within 30 days after ileostomy closure.Bowel obstruction is defined as productive vomiting or the need of gastric tube placement or absolute constipation with a duration of at least three days. This definition is based on the existing trial by Hasegawa  which prSecondary endpoints are the time needed to perform the procedure, wound infection, rate of re-operation due to anastomotic leakage of the ileostomy closure, time to first tolerance to solid food and first bowel movement, whichever of these occurred last, length of postoperative hospital stay, 30 days and 12 months mortality after ileostomy closure, rate of re-operation and re-hospitalization within one year due to bowel obstruction, costs of surgical procedure for the institution , quality of life (EuroQol 5 D).Three out of, five visits are documented by the investigator in each center during in hospital phase , followed by two telephone interviews for 30 days and 12 months follow up after operation . A paper based CRF is used to collect the data. The investigator, or designated representative, should complete the CRF pages as soon as possible after information is collected, preferably on the same day that a trial subject is seen for an examination, treatment, or any other trial procedure. Any outstanding entries must be completed immediately after the final examination. An explanation should be given for all missing data.The completed CRF must be reviewed and signed by the investigator named in the trial protocol or by an authorized sub-investigator. To ensure that the database reproduces the CRF correctly, the Institute of Medical Biometry and Informatics Heidelberg (IMBI) accomplishes a double entry of data. Completeness, validity and plausibility of data are examined by validating programs, which thereby generate queries. The investigator or the designated representatives are obliged to clarify or explain the queries. At the end of the trial, the principal investigator will retain the originals of all CRF.The data will be managed and analyzed in the joint unit of SDGC and IMBI in accordance with the appropriate standard operating procedures (SOP).Monitoring is carried out in accordance with ICH E6 (GCP) and standard operating procedures of the Coordinating Centre for Clinical Studies (KKS) Heidelberg. Two different monitoring strategies are used within as the HASTA trial is part of the ADAMON project , which Half of the trial centers, chosen at random, are monitored by a risk-adapted monitoring strategy which is described in a trial specific monitoring manual. Participating centers are activated with an initiation visit by the monitor, who will hand-out the prepared investigator site file. All relevant trial issues are discussed and personnel are trained on trial specific procedures, documentation and web-based randomization. The monitor is in regular contact by phone or e-mail with all participating centers to follow progression of the study, protocol adherence, and to discuss trial related problems. Further monitoring visits are carried out during the course of the trial for source data verification of relevant core data, i.e., patient informed consent, inclusion/exclusion criteria, performed treatment, primary and secondary endpoints and serious adverse events. Frequency of regular monitoring visits depends on the number of recruited patients and the performance of each trial center. Every trial center is visited at least once during the trial. Close-out visits are not as a standard foreseen in the centers.The remaining participating centers will be monitored by a "full" or 100% monitoring (control-intervention for ADAMON) including: initiation visit, first regular monitoring visit (after inclusion of first patient), further regular monitoring visits , 100% source data verification for all included trial patients, close-out visit.In addition, an efficient central supervision of the clinical trial is established  for both strategies. Investigators in the participating centers will support the monitor in his/her activities.A final audit is scheduled in the participating centers. These audits are carried out to check whether the conduct of the study is in accordance with ICH-GCP regulations. Independence from the trial personnel involved in HASTA is guaranteed for every auditor. Investigators have agreed to give auditors free access to all relevant documents. Based on the results of these audits the two monitoring strategies will be compared.According to ICH-GCP the term "adverse event" covers any clinically relevant sign, symptom, syndrome, illness that appears or worsens in a subject during the period of observation in the clinical trial and that may impair the well-being of the subject.Adverse events fall into the categories non-serious and serious. Non-serious adverse events will not be documented in HASTA trial. The following conditions and treatments are expected after the initial operation and will therefore not be classified as AE: pain, nausea, hyper-/hypotension, blood sugar problems, electrolyte imbalances and other lab values out of normal range, if they are not exceeding the duration and extent that can be expected after such an operation.However, all endpoint relevant complications  are explicitly being asked for and documented in the CRF as endpoint (not as adverse events). Any other complications that are considered as clinically relevant by the investigator should be documented in free text.From the day the subject has signed informed consent until the regular end of trial at 12 months follow-up or until premature withdrawal of the patient, all serious adverse events (SAE) must be documented on a "serious adverse event form" available in the investigator site file. Serious adverse events have to be reported by the attending physician to the principal investigator within 5 days after the SAE becomes known.It is the responsibility of the principal investigator to register all SAEs and to check incoming SAEs as to completeness, correctness and plausibility.In case of any irregularities for example concerning the frequency or type of SAE reported the principal investigator will inform the members of the Independent Data Safety Monitoring Board (DSMB) without delay. At least once every 12 months, the DSMB will receive a written safety report. The members of the DSMB then report the result of the benefit/risk assessment to the principal investigator and will give appropriate recommendations concerning the continuation of the trial.Analysis of safety related data is performed with respect to frequency of SAE in both treatment groups and frequency of SAE stratified by causality.Each patient's allocation to the different analysis populations  according to the intention-to-treat (ITT) principle, per protocol (PP) analysis set, safety analysis set) will be defined prior to the analysis. The allocation will be documented in the statistical analysis plan. During the data review, deviations from the protocol will be assessed as „minor" or „major". Major deviations from the protocol will lead to the exclusion of a patient from the PP analysis set.The null-hypothesis is assessed by testing the intervention effect in a logistic regression model that takes into account the covariates "intervention" (hand-suture/stapler) and "skill of surgeon" (board certificate yes/no). Due to the high number of targeted centers (approximately 20), the variable "center" for which randomization was stratified is not planned to be additionally included in the model. A two-sided type I error rate of will be applied.Confirmatory analysis will be primarily based on the FAS which is consistent with the intention-to-treat (ITT) principle by including all patients who were randomized to the two groups. This approach reflects the idea that the study should match as close as possible to the conditions in clinical practice.If a patient discontinues from the study prematurely, missing data with respect to the primary outcome variable will be replaced by ICA-r method described by Higgins et al. (2008) .In addition to the evaluation of the FAS, a PP analysis will be performed including all randomized patients without major protocol violations.p-values for treatment group comparisons and associated 95% confidence intervals. Possible center effects will be analyzed, too. All additional evaluations will be described in the statistical analysis plan, which will be fixed prior to database closure.The secondary variables will be analyzed descriptively by tabulation of appropriate measures of the empirical distributions, descriptive The homogeneity of the treatment groups will be described by comparison of the demographic data and the baseline values.Data management and analysis will be performed using SAS, version 9.1 or higher.The principal investigator has the right to terminate the trial and to remove all trial material from the trial center at any time in consultation with the trial statistician and the steering committee. For any questions concerning safety of trial subjects the DSMB should be consulted.Reasons that may require trial termination include potential health hazard caused by the study intervention and indicated by the prevalence or severity of adverse events, unsatisfactory patient enrollment with respect to quality or quantity or data recording is severely inaccurate or incomplete. Also, new external evidence may necessitate termination of the trial.There are several institutions that ensure safety, transparency and reproducibility of the trial. The steering committee consists of eight independent members . Tasks of the steering committee are review of the trial protocol before the beginning of the trial and evaluation of Data Safety Monitoring Board (DSMB) recommendations regarding premature study discontinuation. The DSMB consists of three independent members . In case of any irregularities for example concerning the frequency or type of SAE reported the principal investigator will inform the members of the independent DSMB without delay. At least once every 12 months, the DSMB will receive a written safety report. The members of the DSMB then report the result of the benefit/risk assessment to the principal investigator and will give appropriate recommendations concerning the continuation of the trial.78% of centers participating in the HASTA trial are non-university hospitals coming from the organization of certified German bowel centers, some of them with little trial experience. Therefore, we organized a 2-day investigators meeting with following topics on the agenda: introduction to the trial protocol and its rationale, discussion of surgical procedures, preparation for study initiation and patient documentation. All partners from the trial management presented their responsibilities: biometry, data management, monitoring, project management and surgical coordination. To stan dardize surgical procedures, an operative training session was held in a special surgical laboratory. Participants were thus given the opportunity to practice surgical techniques for stapling and hand-suture. 17 out of 18 participants returned the SDGC questionnaire for evaluation of content and rhetoric of the speech as well as for the printed handout, giving a rating between 1.2 and 2.2 (1 is the best end and 6 is the worst end) to all speakers. Yet, the operative session was unanimously considered the highlight of the meeting. Participants also commented very positively that ample time was given for discussion and in question and answer sessions. Thus the meeting was very well accepted by all participants . The trial will also be carried out in compliance with national legal and regulatory requirements. The medical secrecy and the German Federal Data Protection Act will be observed. After termination the trial will be reported in accordance with the CONSORT statement .Patients receive complete oral and written information on the trial by a medical doctor and a written informed consent has to be signed.http://www.germanctr.de/index_de.html) with a unique identification number (DRKS00000040) on October 27, 2008.Before the start of the trial, the clinical trial protocol, informed consent document, and any other appropriate documents had been submitted to the independent ethics committee (IEC). The documents were approved by the independent ethics committee of the University of Heidelberg Medical School on September 23, 2008. Secondary approval is sought from all local ethics committees of the participating centers. The IEC must be informed of all subsequent protocol amendments. Amendments must be evaluated to determine whether formal approval must be sought and whether the informed consent document should also be revised. The investigator must keep a record of all communications with the IEC. The trial was registered by the German Clinical Trial Register (The trial management is committed to writing a scientific publication in any case, even if the trial is stopped early. The design of the trial and the trial results will be published and the authorship will be assigned by the trial management. Representatives of the four highest recruiting trial centers will act as co-authors and each participating center will be mentioned.The first center was initiated in January 2009, the first patient was randomized in February 2009. 334 patients should be randomized within 20 months. After a follow-up period of 12 months the trial should be terminated in October 2011. Figure If there are two or more treatment options for one clinical condition a randomized, controlled trial with a clinically relevant endpoint should determine which is more beneficial to the patient . ConcernAE: Adverse Event; BMBF: German Federal Ministry of Education and Research; CRF: Case Report Form; DGCH: German Surgical Society; DSMB: Data Safety Monitoring Board; FAS: Full Analysis Set; GCP: Good Clinical Practice; ICH: International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use; IEC: Independent Ethics Committee; IMBI: Institute of Medical Biometry and Informatics; ITT: Intention-to-treat; KKS-HD: Coordinating Centre for Clinical Trials - University of Heidelberg; LAR: Low anterior resection; PP: Per Protocol; RCT: Randomized Controlled Trial; SAE: Serious Adverse Event; SDGC: Study Center German Surgical Society; USP: United States Pharmacopoea.All authors disclose any financial and personal relationships with other people or organizations that could inappropriately influence their work within this project. The authors declare that they have no competing interests.TL and CMS participated in the design of the study, wrote the manuscript and had full access and responsibility for all data. IR coordinated the trial and participated in writing the manuscript. TK, OT, RH, MK and TS contributed to patient accrual and helped to draft the manuscript. TB and MK participated in the design of the study, perform the statistical analysis and helped to draft the manuscript. MB supervised the study conduct and revised the manuscript draft. JW conceived the study idea and participated in writing the manuscript. All authors read and approved the final manuscript.


Within the central auditory system, the central nucleus of the inferior colliculus (ICC) is a station where all stimulus information converges. Furthermore, it is a target for auditory prostheses due to its tonotopic order and surgical accessibility . To bettVocalizations, being natural stimuli and showing a variety of spectral and temporal modulations, are particularly interesting and can elicit responses which are not triggered by pure tones, clicks, white noise or other artificial simplified sounds . ConspecWe investigated response similarity along these two dimensions of the ICC for multi-unit thresholded spike trains, local field potentials and voltage traces. We evaluated the correlation dependencies of multi-unit pairs on their spatial distance, difference in best-frequency and similarity of the frequency tuning curves. The presence of a distributed code would imply that the interplay of several multi-units leads to better representation of the complex sound. We have tested this by comparing neural discrimination between pooled sets of simultaneously recorded responses to non-simultaneously recorded ones. The latter was obtained by randomly shuffling the trials. We used linear discriminant analysis for the classification. The extracted features were firing rates of time windows over the duration of the longest vocalizations.We found that the averaged correlation of single spike-trains is much lower than correlation of poststimulus time histograms (PSTH). This is partly due to the high trial-trial variability which is averaged out in the PSTHs. Correlation decreases with distance ( 'μm' and 'best frequency') along the tonotopic gradient, see Figure There is no significant difference in neural discrimination performance for simultaneous and non-simultaneous responses which could be found from the multi-unit responses.


Pulpal and periodontal problems are responsible for more than half of the tooth mortality. There are some articles published in the literature about this issue. Many of them are quite old. There has been also lack of knowledge about the effect of endodontic treatment on the periodontal tissue healing and suitable treatment interval between endodontic and periodontal treatments. In this case report, different kinds of endo-perio lesion were treated with sequential endodontic and periodontal treatment. The follow-up radiographs showed complete healing of the hard and soft tissue lesions. The tooth with endo-perio lesions should be evaluated thoroughly in terms of any cracks and fracture, especially furcation areas for a long term prognosis. In this case report, it was showed that 3 months treatment intervals between endodontic treatment and periodontal surgery has no harmful effect on periodontal tissue healing. Key words:Endo-perio lesion, furcation, mandibular molar, bone graft, crack line, treatment interval. Dental pulp and periodontal tissues are closely related that are ectomesenchymal in origin . The pulPulpal and periodontal problems are responsible for more than half of the tooth mortality . The relThe vast majority of pulpal and periodontal diseases are caused by bacterial infection. It has been suggested that cross-infection between the root canal and the periodontal ligament can occur via the anatomical  and non-physiological pathways  . These pThe classification of endo-perio lesions by Simon et al. is that primary endodontic diseases, primary periodontal diseases and combined disease including primary endodontic disease with secondary periodontal involvement, primary periodontal disease with secondary endodontic involvement and true combined disease . This clThe main factors to take into account for treatment decision-making are pulp vitality and type and extent of periodontal defect. The differential diagnosis of endodontic and periodontal diseases can be challenged but a correct diagnosis has a vital importance so that appropriate treatment can be provided.The aim of this study was to present the diagnosis and management of different types endo-perio lesions and emphasize the importance of the correct treatment sequence.- Case 1A 21-year-old male patient, with a noncontributory medical history was referred for the treatment of pain and intraoral localized swelling in the left mandibular first molar. Clinical and radiographic examinations revealed large caries and periapical and furcal lesions related to tooth #36  and stabilized in the furcation area Fig. . PrimaryThe endo-perio lesions present challenges to clinicians as far as diagnosis and prognosis of the involved teeth are concerned. Correct diagnosis is essential prerequisite to determine the treatment and long-term prognosis. Diagnosis of primary endodontic disease and primary periodontal disease usually presents no clinical difficulty. The first step for proper diagnosis is the vitality tests. Although the vitality test cannot provide the histological status of the dental pulp, their ability to register pulp vitality is quite satisfied. The ability of vitality tests to detect non-sensitive reaction represented a necrotic pulp was reported as 89% with the cold test and 88% with the elec-trical test (The infected root canal can cause a chronic inflammatory reaction which extends the gingival sulcus and drains through the sinus tracts. If the rest of the dentition is periodontally healthy and any root cracks and fractures has been ruled out, healing of the periodontal tissues can be expected after endodontic treatment as it was observed in case 1 and 2. Therefore, further treatment requirements should always considered followed by an observation period of at least 3 months. Conversely, there has been a debate in the literature about the impact of the endodontic treatment on the healing potential of the periodontium. Some studies have been reported that endodontic treatment may cause an inhibitory effect on periodontal wound healing ,10 whileProper endodontic treatment is a key factor for treatment success. Poor endodontic treatment allows canal re-infection and in this way, leads to the treatment failure . MoreoveIn this case report, the cleaning and shaping of the root canals were performed in combination with irrigation with sodium hypochlorite and additional interappointment calcium hydroxide medication to render the root canal system free of cultivable bacteria.Calcium hydroxide is bactericidal, anti-inflammatory and proteolytic and inhibits resorption and favors repair. It also inhibits periodontal contamination from instrumented canals via patent channels connecting the pulp and periodontium before periodontal treatment removes the contaminants. We observed that the sinus tracts extending into the furcation area were disappeared 1-2 weeks later and the canals are eventually filled with a conventional obturation.When periodontal and pulpal lesions occur concurrently, it has been described as combined lesion. In this condition, the treatment and prognosis of the tooth are different from those of teeth involved with only primary endodontic disease. The tooth now requires both endodontic and periodontal treatments. If the endodontic treatment is adequate, the prognosis depends on the severity of the periodontal damage and the efficacy of periodontal treatment. If an increased periodontal tissue destruction occur and cannot be replaced with periodontal regenerative techniques, the extraction of the tooth seems the only solution. The bony lesion of case 4 had endodontic and periodontal lesions and first treated with endodontic therapy. Treatment results were evaluated in 2–3 months and then periodontal treatment was considered. This sequence of treatment allows sufficient time for initial tissue healing and better assessment of the periodontal condition. This case demonstrates that proper diagnosis, followed by removal of etiological factors and utilizing the guided tissue regeneration technique combined with osseous grafting, will restore health and function to a tooth with severe attachment loss caused by an endo-perio lesion.The ideal interval between the endodontic treatment and periodontal surgery has also been challenged by controversial findings. It was reported that root canal treatment performed 2.5 months before periodontal surgery not to impair periodontal healing . MirandaThe treatment planning given in this case report can guide the clinician to deal with the treatment of different types endo-perio lesions. In this case report, treatment strategies were given in related to the different kinds of endo-perio lesions. Treatment outcomes will be more predictable if the clinician has more through knowledge about the diagnosis, treatment sequences and intervals. Thereby, the immediate and true management of the endo-perio lesions can impede the loss of the natural tooth and delay the more complex treatments.


Neutrophils release extracellular traps (NETs) in response to a variety of inflammatory stimuli. These structures are composed of a network of chromatin strands associated with a variety of neutrophil-derived proteins including the enzyme myeloperoxidase (MPO). Studies into the mechanisms leading to the formation of NETs indicate a complex process that differs according to the stimulus. With some stimuli an active nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is required. However, assigning specific reactive oxygen species involved downstream of the oxidase is a difficult task and definitive proof for any single oxidant is still lacking. Pharmacological inhibition of MPO and the use of MPO-deficient neutrophils indicate active MPO is required with phorbol myristate acetate as a stimulus but not necessarily with bacteria. Reactive oxidants and MPO may also play a role in NET-mediated microbial killing. MPO is present on NETs and maintains activity at this site. Therefore, MPO has the potential to generate reactive oxidants in close proximity to trapped microorganisms and thus effect microbial killing. This brief review discusses current evidence for the involvement of reactive oxidants and MPO in NET formation and their potential contribution to NET antimicrobial activity. Neutrophils release extracellular traps (NETs) in response to a diverse range of stimuli including a variety of microorganisms, microbial products, and chemokines (refer to the review by 2O2) leading to the formation of a variety of toxic oxygen derivatives, especially those formed by MPO-catalyzed reactions. Both the NADPH oxidase and MPO have been implicated in the regulation of NET formation. However, the specific reactive oxygen species (ROS) required remains to be clarified.Activated neutrophils produce large amounts of superoxide (2O2 forming the strong oxidant hypochlorous acid (HOCl), the prime mediator of oxidative killing in the phagosome (2O2) to generate HOCl in close proximity to trapped bacteria, thus providing a prospective mechanism for oxidative NET-mediated killing. In this short review, we summarize experimental evidence for the involvement of ROS and MPO in the regulation of NET formation and discuss their potential contribution to NET antimicrobial activity.Myeloperoxidase catalyses the oxidation of chloride by Hhagosome . MPO is hagosome  and has Studies into the mechanisms of NET formation (NETosis) indicate a complex process that differs depending on the stimulus. Given the variability in NET inducers  the exisStaphylococcus aureus, an early phase of NET release induced by secreted bacterial products is independent of the oxidase and of cell death, with dependency on these increasing over time  whose NADPH oxidase is non-functional . Inhibitver time . The latver time .2O2 restores the ability of CGD neutrophils to produce NETs . However, even though an NO donor has been shown to induce NETs , the lowFigure 1A).There is growing evidence that MPO is necessary for PMA-stimulated NETosis and the majority of studies indicate that an active enzyme is required. Inhibition of MPO decreases PMA-stimulated NETs  and neutPseudomonas aeruginosa, S. aureus, or Escherichia coli NET induction . As yet these are not well characterized. During phagocytosis, activation mainly occurs at the phagosomal membrane .Activation of the neutrophil NADPH oxidase leads to the production of a variety of ROS. Assigning which are required for NETosis is not simple. The site of oxidase activation and degree of degranulation, which vary depending on the stimulus, affect the relative amounts of the different ROS produced as well as access to different cell constituents. With soluble stimuli, such as PMA, and non-phagocytosed particulate stimuli, activation largely occurs at the plasma membrane although some occurs at intracellular sites . The production of HOCl in the extracellular environment requires MPO release, the timing or level of which varies with stimulus. In the phagosome, due to high MPO concentrations, essentially all of the H2O2 should react with MPO before it can diffuse out . However, the generation of these oxidants by neutrophils is considered to be very low  which is taken up by endocytosis  to neutrophils has been shown to modestly increase PMA-induced NETs . This woproduced . At presAs the major strong oxidant produced by MPO, HOCl is a potential candidate for the oxidant responsible for MPO-dependent NET formation. Indeed, addition of HOCl to neutrophils has been reported to induce NETosis . However1O2) has been implicated on the basis that NETs were observed after 1O2 was generated using irradiated Photofrin . MPO inhibition and a potent HOCl scavenger prevented killing . Therefore, NET-MPO has the potential to generate HOCl and effect microbial killing. At a site of inflammation, neutrophils that have formed NETs will no longer be producing ROS. However, during inflammation there is continued infiltration and activation of neutrophils which should provide the H2O2 required. The close proximity of NET-MPO to trapped microorganisms would be expected to facilitate exposure of microbes to lethal concentrations of HOCl and avoid all the oxidant being scavenged by the surrounding media. In vivo imaging using HOCl sensitive probes and differential fluorescent detection of live/dead bacteria would confirm if this occurs in living organisms.Myeloperoxidase is present on NETs  placing There is good evidence that the enzymatic processes of the NADPH oxidase and MPO are important in NETosis but elucidation of the specific ROS and their reactions that regulate NET formation requires further investigation. While the use of scavengers and inhibitors is a useful aid to the study of ROS in NET formation, interpretation of results is confounded by limitations of specificity and getting sufficient concentrations to intracellular locales where the critical oxidant generation may occur. The intracellular pathways leading to chromatin decondensation and NET release are still being worked out. Once this information becomes available, the involvement of oxidants in individual steps can be investigated and a clearer picture should emerge.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Due to its anatomical features, the chorda tympani nerve (CTN) is sometimes sacrificed during middle ear surgery, resulting in taste dysfunction. We examined the effect of placing an artificial nerve conduit, a polyglycolic acid (PGA)-collagen tube, across the gap in the section of the resected chorda tympani nerve (CTN) running through the tympanic cavity.The CTN was reconstructed with a PGA-collagen tube in three patients with taste disturbance who underwent CTN resection. To evaluate the effect of the reconstruction procedure on the patients' gustatory function, we measured the patients' electrogustometry (EGM) thresholds. The patients were followed-up for at least two years.Gustatory function was completely restored in all of the patients after the reconstruction. The patients' EGM thresholds exhibited early improvements within one to two weeks and had returned to their normal ranges within three months. They subsequently remained stable throughout the two-year follow-up period. In a patient who underwent a second surgical procedure, it was found that the PGA-collagen tube used in the first surgical procedure had been absorbed and replaced by new CTN fibers with blood vessels on their surfaces.These results suggest that reconstruction of the CTN with an artificial nerve conduit, a PGA-collagen tube, allows functional and morphological regeneration of the nerve and facilitates the recovery of taste function. PGA-collagen tubes might be useful for repairing CTNs that are resected during middle ear surgery. Further research is required to confirm these preliminary results although this is the first report to describe the successful regeneration of a nerve running through an aerial space. The chorda tympani nerve (CTN) contains primary afferent nerve fibers that transmit taste information signals from the anterior two thirds of the tongue to the solitary nucleus in the medulla oblongata. The CTN leaves the facial nerve and runs through an aerial space of the middle ear Restoring severed nerves with achieving sufficient functional recovery continues to be a clinical challenge. Attempts have been to use various artificial nerve conduits as alternatives to autografts for regenerating severed peripheral nerves This study was approved by the Institutional Review Board at Nara Medical University Hospital. Participants provided their written informed consent to participate in this study. There are no financial interests or potential conflict of interests in this study.Three patients who preoperatively presented with dysgeusia (feeling decreased sweetness) were included in this study. Patient 1 was a 52-year-old male who presented with a three-month history of taste disturbance due to a cholesteatoma involving the CTN. Patient 2 was a 33-year-old male who presented with taste disturbance due to a temporal bone fracture that had lasted for three months. Patient 3 was an 18-year-old female with a cholesteatoma who had a five-month history of unilateral gustatory dysfunction. Reconstruction of the CTN with an artificial nerve conduit, a polyglycolic acid (PGA)-collagen tube, was performed for each patient who underwent the resection of CTN that was strongly affected by the lesion (cholesteatoma sac or ossicles dislocation). To evaluate the effect of the reconstruction on the patient's gustatory function, we measured the electrogustometry (EGM) threshold. The patients were followed-up over at least two years, although patient 1 had never come to our clinic in a period ranging from 4–17 months after the surgery.The artificial nerve conduit was composed of a biodegradable tube filled with biodegradable filaments. The tube framework was made of a cylindrically woven PGA mesh, the outer and inner surfaces of which were coated with amorphous collagen layers. Microscopic appearance and ultrastructure of the conduit as observed through scanning electron microscopy (SEM) are shown in The surgery was performed under surgical microscope with retroauricular incision. The nerve gaps produced by the resection of the CTN measured seven, five, and seven mm in length in patients 1, 2, and 3, respectively. PGA-collagen tube was trimmed to appropriate length (two mm longer than the gap) to fit the nerve gap . The resGustatory function was assessed with electrogustometry (EGM) using an electrogustometer , which is a more reliable and objective method of quantitatively evaluating taste function The nerve gaps produced by the resection of the CTN measured approximate seven mm in length in all three patients. The patients' EGM thresholds before and after CTN reconstruction with the PGA-collagen tube are shown in On the other hands, the patients' sweet taste disturbance as a primary subjective symptom had reached the normal feeling by 2 postoperative weeks in patient 1, three months in patient 2, and one month in patient 3.No adverse events including middle or inner ear dysfunction were observed in any of the patients.A 52-year-old male presented with a three-month history of taste disturbance (feeling decreased sweetness on the right side of his tongue) and a two-month history of hearing loss in his right ear. A physical examination detected a white cholesteatoma mass and the formation of inflammatory granulation tissue in the pars flaccida over the manubrium of the malleus. A CT scan obtained with the bone window setting demonstrated the presence of a soft-tissue mass in the epitympanum and tympanic antrum together with ossicular erosion.The patient underwent surgery to remove the cholesteatoma. During surgery, we found that a cholesteatoma sac occupied the attic of the ear and antral cavity, and ossicles including the malleus and incus had been destroyed. The cholesteatoma sac was attached to the CTN, and dissection of the sac suggested that it had invaded the nerve fibers, as indicated in st surgery.  demonstrated functional recovery of the regenerated nerves at a growth rate of 1–2 mm/day Few studies have reported on the time course of the findings of EGM, a quantitative gustatory function test In patient 1, an index case, during the second surgical procedure, a restiform strand covered with blood vessels, which seemed to be composed of nerve fibers, was detected at the PGA-collagen tube implantation site. There are reports describing that the reconstructed site with PGA collagen tube had been replaced by a white linear tissue on gross view in animal experiments. This observation, which could be viewed macroscopically, has been suggested to be an evidence for regenerated nerve fibers, and hence could support our surgical macroscopic finding for suggesting the CTN regeneration As the cholesteatoma sac that was pressing down on the regenerated nerve was removed, the patient's gustatory function returned to normal in the early postsurgical course. Therefore, the morphological nerve fibers seen during the second surgical procedure probably had the potential to transmit gustatory information and represented a functionally regenerated CTN. The results from our second look surgery strongly suggest that reconstruction of CTN with a PGA-collagen tube in our first surgery allows a regeneration of the nerve.Furthermore, no adverse events, including middle or inner ear dysfunction causing hearing loss, tinnitus or dizziness were observed in any of the patients due to the reconstruction with PGA-C tube. PGA, a bioabsorbable substance, generally used as surgical suture material have been proved to be safe although PGA materials have not been applied in the otologic surgery. It was reported that Poly-lactic/glycolic acid placed on the round window niche for drug delivery to the inner ear had no significant adverse effects in the middle and inner ear except for temporary hearing loss These results suggest that reconstruction of the CTN with an artificial nerve conduit, a PGA-collagen tube, allows functional and morphological regeneration of the nerve and facilitates the complete recovery of taste function. Therefore, PGA-collagen tube might be a useful alternative device for a repair of the CTN section during middle ear surgery. This is the first report to describe the successful regeneration of a nerve running through an aerial space. However, further research compared with control is required to confirm these preliminary results obtained from low number of patients.


AbstractBroad-scale patterns of subterranean diversity are a fascinating but neglected part of biodiversity research. Carabid beetles adapted to belowground habitats form a particularly species-rich part of the subterranean fauna. We studied large-scale diversity patterns of these belowground carabids across the western Palaearctic and evaluated potential impacts of historical and contemporary environmental conditions on the distribution of these taxa, using available species richness and environmental data at country level. Regression modelling and variation partitioning showed a strong relationship between species richness and range in elevation. Potential effects of climatic variables, mainly those related to ambient energy input, were much weaker. We discuss the implications of this combination of effects, which suggests, concordant with the absence of subterranean carabids in northern and highest richness in southern Europe, a strong prevailing influence of historical processes on current richness distributions of these taxa. Previous studies did not provide clear indications for such an influence. In contrast to more mobile and widespread carabid beetles, dispersal limitation due to high adaptation of belowground carabids to subterranean habitats has probably hindered their re-colonization of former permafrost and glaciated regions. Hotspots of highest belowground diversity are located in regions with an assumed long-term stability of environmental conditions, correlating with patterns of other dispersal-limited taxa such as many endemic plants. Our study provides important new information in the discussion of potential determinants of the distinct geographic patterns of belowground diversity. Moreover, it contributes to a better understanding of range size related differences previously found in the distribution of diversity and environmental dependencies of widespread and range-restricted species within the highly diverse carabid beetles. Studies on the spatial patterning of biodiversity and its potential determinants have gained much attention over the last decades, especially in light of global change and its assumed effects on the distribution and survival of many species . In thisHowever, reduced dispersal abilities due to their strong habitat specialization also suggest that especially processes and environmental conditions over historical times have played important roles in the survival and present distribution of these species. Regions with high numbers of subterranean species have probably been subject to lower variability in environmental conditions over long time periods and a higher persistence of ecosystems than other western Palaearctic regions .PageBreak and endemic species of carabid beetles in the western Palaearctic, probably due to differences in the dispersal abilities of these taxa. Comparison of these patterns to those of the strongly range-restricted carabids living in belowground habitats can help to extend our understanding of the distribution of diversity and the possible mechanisms behind such range-size dependent diversity patterns.About 50% of the terrestrial fauna in subterranean habitats are beetles . With moAphaenopidius kamnikensis Drovenik 1987, a carabid until recently known to occur only in caves; Limnastis) were not treated as part of the belowground fauna.The aim of our study was to analyse spatial patterns in the species richness of belowground carabids and their potential environmental determinants on a large scale across Europe and North Africa. Distinguishing between the carabid fauna of deeper soil horizons, beetles of the so-called superficial underground compartment  on the richness pattern of belowground carabids. Spatial, topographic and climatic factors might explain similar proportions of the variability in the observed richness patterns. Our approach allows us to handle the non-independence of predictor variables, which might show the same autocorrelated pattern but relate to different conceptual frameworks in the explanation of diversity patterns, and thus to identify the isolated iariables . For eacariables . Variatiariables . We inclPageBreakran’s I values of zero indicate absence of spatial autocorrelation, whereas larger or smaller coefficients  show the degree of positive or negative autocorrelation between neighbouring sampling units. Non-significant values of Moran’s I coefficients after fitting the explanatory variables indicate that the variables selected well account for the spatial pattern in the richness data  and SAM 2.0 .The distribution of species richness of carabids adapted to belowground habitats showed a clear and significant latitudinal gradient across the western Palaearctic . RichnesSpecies numbers decreased towards northern Europe and North Africa  and mostPageBreak in the distribution of subterranean carabid diversity and that modelling results are not affected by spatial autocorrelation , less strongly with richness of widespread species  and most strongly with richness of endemic carabids . It was also highly correlated with species richness of vascular plants  across the western Palaearctic.PageBreake superficial underground compartment (MSS; The spatial analysis of belowground carabids clearly identifies southern Europe, and especially Italy, as the region with highest species richness in the western Palaearctic. Generally, this region has been classified as one of the hotspots of overall terrestrial troglobiont diversity based on the comparison of local species numbers from single caves  and froment MSS; , and thuSpecies richness of carabid beetles adapted to belowground habitats significantly and most strongly co-varied with range in elevation. To a certain extent, this might reflect effects of habitat heterogeneity and availability , as mounPageBreakisolated refuges north of the Holdhaus-line (Anillus species recorded in park locations of Belgium (Concerning the distribution of hotspots of overall troglobiont diversity in Europe, aus-line , furtheraus-line . In cont Belgium  and Germ Belgium  was prob Belgium .As mentioned above, the influence of dispersal limitation might also become evident from the fact that current climate accounted for much smaller amounts of explained variation than elevation range in both single regressions as well as in regression modelling. Species with well-developed dispersal abilities are assumed to have tracked post-Pleistocene climate changes to a certain degree, and high co-variation between species richness of many taxa and climatic variables support this view (reviewed by PageBreakAt least at the coarse scale of our analysis, we did not find evidence for the assumptions of


We have used an end-to-end ecosystem model to explore responses over 30 years to coastal no-take reserves covering up to 6% of the fifty thousand square kilometres of continental shelf and slope off the coast of New South Wales . The model is based on the Atlantis framework, which includes a deterministic, spatially resolved three-dimensional biophysical model that tracks nutrient flows through key biological groups, as well as extraction by a range of fisheries. The model results support previous empirical studies in finding clear benefits of reserves to top predators such as sharks and rays throughout the region, while also showing how many of their major prey groups  experienced significant declines. It was found that the net impact of marine reserves was dependent on the pre-existing levels of disturbance (i.e. fishing pressure), and to a lesser extent on the size of the marine reserves. The high fishing scenario resulted in a strongly perturbed system, where the introduction of marine reserves had clear and mostly direct effects on biomass and functional biodiversity. However, under the lower fishing pressure scenario, the introduction of marine reserves caused both direct positive effects, mainly on shark groups, and indirect negative effects through trophic cascades. Our study illustrates the need to carefully align the design and implementation of marine reserves with policy and management objectives. Trade-offs may exist not only between fisheries and conservation objectives, but also among conservation objectives. Marine reserves (i.e. no-take areas) are widely used as a tool for marine conservation. Recent reviews demonstrate, on average, positive effects of reserve protection on biomass, numerical density, species richness and size of organisms within their boundaries e.g. Until recently, modelling of MPA effects has mainly focussed on fisheries outcomes rather than conservation outcomes and primarily focussed on single species models  and key biological processes. Temperatures and salinities within each cell and three-dimensional physical exchanges between cells were estimated at every time-step utilising archived output from a data-assimilating global ocean circulation model referred to as the Bluelink Reanalysis or BRAN The model included 48 biological groups ranging from phytoplankton and bacteria through to sharks and whales . Selecti−3 of nitrogen and silica, which are the limiting elements in the system). Higher trophic levels were followed using an age-structured formulation that allowed for changes in reproduction and mortality that may be critical in the response of populations to marine reserves . The demersal shallow territorial group was sedentary (i.e. could not move from one box to the others), and a limited set of groups  had a foraging behaviour that allowed them to move among boxes to optimise their potential growth . Other biological processes explicitly represented in the model included consumption and growth, waste production and decomposition, reproduction, habitat dependency, bioturbation and bioirrigation, and predation and other forms of natural mortality. Detailed mathematical formulations for these processes can be found in The functional groups were linked through local trophic interactions and influenced by environmental and habitat conditions in the water column and bottom sediments. Nutrients, planktonic groups and detritus were exchanged between cells on the basis of physical flows estimated from the aforementioned ocean circulation model. The movements of vertebrates were modelled so as to maintain particular distribution patterns, some of which were constant , while others varied through the year . The only exceptions were sharks and rays, for which fishing mortality rates were estimated from the literature.2) or 6.2% (2979 km2) of the total modelled domain (48000 km2). Although they corresponded in location and total area to the real reserves declared off NSW over the past decade (http://www.mpa.nsw.gov.au/), no attempt was made to replicate the complex mosaic of zones with varying degrees of protection. Instead, reserves were idealised as either strictly no-take areas when the reserves covered whole model cells  over the 30-year simulations. These metrics are different from the ones used in field studies, which usually compare one or several sites within and outside of the marine reserves, but with no indication of what is happening at the scale of the whole region.biomass of functional groups expressed as the ratio of the biomass at the end of a given scenario with reserves in place to the biomass at the end of the corresponding baseline scenario with no reserves . While this metric ignores short-term volatility in prices due to factors such as market preferences, international influences and scarcity, it captures any broad trends in catch composition between high and low value species.Change in the functional diversity index (Q90 defined below) expressed as the ratio of the functional diversity index at the end of a given scenario to the functional diversity index at the end of the corresponding baseline scenario. Q90 is derived from Kempton's diversity index and adapted to measure functional biodiversity Change in the Centroberyx affinis) collapsed irrespective of their presence . In most of these cases the relative changes increased roughly in proportion to the size of the area protected , the effects of reduced fishing in reserves necessarily pertained to the entire population. However, even in the case of more sedentary groups, such as demersal omnivores, there was sufficient dispersal in the model for positive effects to extend along most of the coast rather than being restricted to the reserve areas.For migratory sharks, such as grey nurse (Centroberyx affinis fished offshore), it resulted in a net decline in scenarios 2 and 3  such as demersal herbivores, increases in predation only partially offset the benefits of reduced fishing pressure. For groups not being fished in the coastal zone, such as demersal territorials  or redfish , much of which occurred in estuarine fisheries where the reserve coverage was highest. The associated decline in economic value of catches was smaller still as reductions in total catch were partially offset by increases in the proportion of high value fish groups, such as the shallow demersal omnivores in the scenarios 2 and 3, or the shallow demersal herbivores in the scenarios 5 and 6 . In the Removing low fishing from reserves caused a very small increase in the functional diversity index , while rIn this paper, we used an Atlantis ecosystem model of the NSW continental shelf and upper slope to test the effects of coastal no-take marine reserves at a large regional scale over a 30-year period. The results were analysed using metrics related to the higher functional groups  over the 30-year simulations, i.e.: changes in biomass for each functional group and in the functional biodiversity index (Q90), both of which were computed for the whole model domain. This modelling approach contrasts with experimental studies on the impact of marine reserves , or high fishing pressure (i.e. double the 1976 fishing level).Centroberyx affinis). Low fishing levels generated an intermediate level of disturbance in the model that sustained relatively high levels of functional biodiversity The high fishing scenarios (twice the 1976 fishing level) resulted in a strongly perturbed system, where the introduction of marine reserves had clear and mostly direct effects  on biomass and functional biodiversity. However, under lower 1976 fishing level scenarios, the introduction of marine reserves caused both direct positive effects, mainly on shark groups, and indirect negative effects through trophic cascades (e.g. increased predation on shallow demersal territorials and juvenile redfish sensuThe ecosystem response also depended on the size of the protected areas, although to a lesser extent than the disturbance rate. All the groups impacted by the establishment of marine reserves show a biomass response proportional to the size/number of the area protected. This is consistent with the meta-analysis findings of Halpern et al The model results support previous empirical studies e.g. Our study illustrates the need to carefully align the design and implementation of marine reserves with policy and management objectives. Trade-offs may exist not only between fisheries and conservation objectives, but also among conservation objectives. In a low fishing context, functional biodiversity might be negatively affected by the recovery of large predators, and therefore might not be the best indicator of marine reserve performance. This finding is particularly pertinent given that reserve areas are often selected to minimise conflicts with existing fisheries.The implications of our model results for the effects of marine reserves on species diversity are uncertain, but interestingly, Hockey and Bosman


Picea abies) and silver fir . We developed tree-ring chronologies from 13 mesic mid-elevation sites (203 trees) and then compared them to monthly temperature and precipitation data for the period 1846–1995. Correlation functions, principal component analysis and fuzzy C-means clustering were applied to 1) assess the climate/growth relationships and their stationarity and consistency over time, and 2) extract common modes of variability in the species responses to mean and extreme climate variability. Our results highlight a clear, time-stable, and species-specific response to mean climate conditions. However, during the previous-year's growing season, which shows the strongest correlations, the primary difference between species is in their response to extreme events, not mean conditions. Mesic sites at mid-altitude are commonly underrepresented in tree-ring research; we showed that strong climatic controls of growth may exist even in those areas. Extreme climatic events may play a key role in defining the species-specific responses on climatic sensitivity and, with a global change perspective, specific divergent responses are likely to occur even where current conditions are less limited.Climate forcing is the major abiotic driver for forest ecosystem functioning and thus significantly affects the role of forests within the global carbon cycle and related ecosystem services. Annual radial increments of trees are probably the most valuable source of information to link tree growth and climate at long-term time scales, and have been used in a wide variety of investigations worldwide. However, especially in mountainous areas, tree-ring studies have focused on extreme environments where the climate sensitivity is perhaps greatest but are necessarily a biased representation of the forests within a region. We used tree-ring analyses to study two of the most important tree species growing in the Alps: Norway spruce ( The growth and distribution of forests and the related roles of forests within the terrestrial carbon cycle are closely intertwined with climate forcing and variability at both short and long time-scales Many studies have shown that some regions and species are more sensitive to climate variations than others Annual radial growth increments of trees are probably the most valuable source of environmental and ecological information for long time periods. These have been used in a wide variety of studies largely conducted in extra-tropical regions from typical climate reconstructions All of these investigations have added valuable insight into species-specific climate/tree growth relationships and ecosystem responses to climate variability over local to continental spatial scales. However, most of the studies were carried out in marginal areas where the expression of the limiting factors for tree species probably reach the maximum, but at the cost of no longer being representative of the broader forested region. In other words, the role of forests within the global carbon cycle as well as the goods and services they provide is usually reduced in many extreme environments, whereas this role is maximized where conditions are less limiting such as, far from the treeline and at mid-latitude or mid-elevation. Nonetheless, even at lower latitudes or lower elevations, climate is still one of the most influential forcing factors for tree growth and ecosystem functioning. This calls for a better understanding of species and forest ecosystem behaviour in more mesic and milder environments. Indeed, knowing long- and short-term species responses to climate variability, where climate is not regularly limiting, is becoming more important for understanding the role of forests under various future change scenarios Picea abies (L.) Karst.) and silver fir . By using a dense network of tree-ring sites within a typical inner Alpine valley, we tryed to test the species sensitivity to mean climate variability and extreme climatic events, not at the limits of the species’ distributions but well within the temperature and precipitation ranges where most spruce and fir forests find their optimal growth conditions.The Alps are one of the most studied areas worldwide and this mountain range now has one of the best networks of high density and high-quality tree-ring We adopted both classical and novel methodological approaches to explore the influences of mean and extreme climate on tree growth. We first computed the climate-growth relationships using correlation functions and then analyzed the common climate response patterns with principal component analysis and fuzzy C-means clustering.All the field studies and sampling were carried out after permissions had been obtained from the Valle D'Aosta regional forests administration and the Gran Paradiso National Park, Italy.Aosta Valley is located in the western Italian Alps. Due to the inner setting within the Alps, the surrounding high peaks and its east-west orientation, the climate is continental and among the driest in the Alps. The mean annual precipitation and temperature are 561 mm and 10.1°C, respectively  Larix decidua Mill.). Norway spruce is one of the most important species, representing 32% of the regional forest biomass and occurs in the montane and subalpine belts growing in pure and mixed forests, mainly with larch at higher elevation. In the western Italian Alps, silver fir is currently under-represented compared to its potential distribution. Indeed, many of the regional forests of the montane belt could potentially be mixed with the occurrence of both fir and spruce. Past human land-use has systematically selected for a few, preferred species causing the progressive disappearance of others, mainly silver fir in most of the sites. Alternatively, where human influence has not been historically significant in the last couple of centuries, forests are denser. This permits the presence of pure, or near-pure, stands dominated by the shade-tolerant silver fir, which overtakes more shade-intolerant species In this region silver fir represents only 3% of the regional tree biomass. It grows mainly on north-facing slopes of the montane belt where it often forms pure stands but also occurs mixed with spruce and European larch  mean sensitivity (MS), a measure of the relative difference in ring widths between consecutive years, adopted to assess the high-frequency variability of the series, ii) the first order serial autocorrelation (AC), a measure of the influence of previous year’s conditions on ring formation , iii) the variance explained by the first principal component (PC1), and iv) the mean correlation between trees (rbar) and the “expressed population signal” (EPS) to estimate the level of year-by-year growth variations shared by trees in the same site. Higher values of PC1 and rbar indicate higher synchronization in the annual growth patterns among sampled trees and better common signal strength by the mean growth chronologies A minimum of two cores per tree were collected at breast height on the cross-slope sides of the trunk from at least 13 trees at each site. We followed the classical dendroecological protocol, selecting only healthy dominant or co-dominant trees with no visible scars or signs of recent injuries in an attempt to enhance the climatic information retained in the tree-ring sequences and reduce to a minimum the possible effects of external influences such as competition, crown suppression or small-scale disturbances. Samples were prepared following standard procedures outlined in Stokes and Smiley th century mean The HISTALP gridded dataset of monthly temperature and precipitation series Relationships between climate parameters and each individual and site chronology were analyzed using Pearson's correlation coefficient (CC) over the 1846–1995 period Principal Component Analysis (PCA) th and 90th percentile, respectively, Finally, to better define the behaviour of the two species, we selected the coldest and warmest years in the 1846–1995 meteorological record following the extreme event definition outlined in the last two IPCC reports  and ii) the most significant correlations for the July and August temperatures of the previous year, which are concurrently the most important common climate forcing between species. Both these emergent features in the climate/growth responses are confirmed by the PCA. Furthermore, they have proven to be stable and consistent throughout the last 150 years after splitting the analyses into the 50-year sub-periods. Climate/growth responses for all the sites are summarized in The above results suggest a clear species-specific separation, yet the two most significant responses (July and August temperatures of the previous year) are similar. The wide range of responses computed for the same months at the individual level are also similar . AnalyseA careful site and tree selection to enhance tree-growth responses to the environmental feature of interest and to maximize age or length of record is the typical mode of sampling in most traditional dendroecological investigations. This approach is appropriate for many types of research in dendroecology Tree-ring statistics for silver fir indicate a slightly higher year-to-year variability and a greater similarity in the annual growth patterns among sampled trees than spruce. These statistics suggest that fir has a higher sensitivity than Norway spruce to environmental (climate) variability and that overall stand growth for fir is better represented by the mean growth chronologies. This is consistent with many previous studies confirming the better capacity of silver fir to record environmental inputs in its tree-ring sequences compared to the more plastic responses of Norway spruce throughout its broader distribution range The key feature that emerges from our analyses of climate/growth relationships in spruce and fir growing in mesic sites in the Alps is the consistent sensitivity of tree growth to climatic conditions in the previous growing season. This has proven to be a common fingerprint for silver fir throughout its distribution area We inspected the tree-ring growth reaction and its partition to extreme climatic events by sharpening the focus on this single seasonal window (July and August temperature). This shows, with mean monthly parameters, both the strongest and most similar relationships between species. The significant and consistent separation  reveals et al. The species-specific sensitivity to climate is not just a matter of extreme weather conditions, as it also emerges clearly when observing the whole profile of the monthly responses. Here, based on results from mesic sites, the PCA detected a significant separation between the two conifers. This is in contrast to temperature- or drought-limited sites where different species frequently show a correspondence among the response profiles, especially for the growing season months et al. These results are in line with previous findings of Kunstler e.g., SO2 emissions from power plants and refineries th century almost never touched the southern side of the Alps vs. fixed-intervals and PCA, can also lead to different results with their different sensitivities in the trend vs. strength detection of the growth/climate relationships.Both of these features, the species-specific responses together with the convergent previous-year climatic sensitivity, were rather stable over time. Several studies in Europe have tested whether climate/growth responses in the two species are stable over time, and the majority reached the conclusion of a temporal instability mainly centred in the last decades It is nevertheless important to underline that several limitations of our study may alter its potential to detect the responses to climate of mid-elevation forest ecosystems. First, our investigation covered just two conifers. Although Norway spruce is the most important tree species in Europe and together with silver fir represents a key component of the forest cover in the montane belt of the Alps, further studies with different taxa and regions are needed to generalize our findings. Second, we did not directly consider the effect of topographic differences in temperature and precipitation on local climate. In such a dissected landscape a downscaled climatology would likely permit subtle differences to be unmasked in the growth-climate analyses. Although the study area can be considered rather small and homogeneous with respect to the whole Alpine region, future investigations covering larger regions could be more robust by coupling high-resolution climatologies and digital elevation models Our results represent a first step in this direction. Indeed, while still adopting the classical dendroecological sampling protocol, we selected mountain sites at lower elevations. Yet we detected the importance of the species-specific climate sensitivity even within the same regional context. This specificity shows in both the mean and extreme monthly growth responses, with the latter more subtly disentangling the distinct taxon-specific behaviour. The traditional model of tree ecophysiology suggests that species-specific growth responses to climate will begin to converge on more stressful sites . However, as we demonstrate here, the corollary is that at less stressful sites more pronounced species-specific growth responses occur. A clearer understanding of the nature of these responses along stress gradients will allow for better estimates of long-term growth and the outcomes of competitive interactions in native mixed species forests. Future forest productivity estimates and species reactions to climate change based on tree-ring growth data should take into account a revised and more comprehensive sampling strategy, data from modal sites, and relationships obtained from mesic habitats. These sites and relationships are so far underrepresented in tree-ring studies despite importance of their spatial extent, and contribution to regional biomass in the carbon cycle.Figure S1Individual responses to climate.(DOC)Click here for additional data file.Table S1Result statistics of the fuzzy C-mean clustering.(DOC)Click here for additional data file.


This is a commentary discussing the article published in Thrombosis Journal by Subramanian et al. . The need for post-operative thromboembolic prophylaxis in orthopaedic surgery is beyond debate. Post-operative thrombosis is prevalent in these patients. In the absence of thromboprophylaxis, the incidence of venographically confirmed deep vein thrombosis (DVT) in the first 7 to 14 days following surgery is about 40-60%. About half of these thrombi become symptomatic. In most cases DVT is diagnosed within a period of two months after the patients’ discharge from hospital [Guidelines on prophylaxis of venous thromboembolism that have been published by at least four different organisations established in the field of medical research, all agree on the need for post-operative prophylaxis -5.Current prophylactic treatment is highly effective, and a significant reduction in the venous thromboembolism (VTE) incidence can therefore be reached by the use of adequate prophylaxis ,7.et al. [et al. [However, despite the various guideline recommendations and readily available efficacious medication, the use of preventive measures against VTE in clinical practice has been found to be sub-optimal in several instances. A retrospective study by Yu et al.  found th [et al.  showed tThrombosis Journal on the 12 month review of a modified protocol using low dose Dabigatran etexilate in postoperative thromboembolic prophylaxis in joint replacement surgery, to deviate from the NICE guideline, seem legitimate [Therefore, the stated rationale and considerations by the authors of the article published gitimate . On the Usually guidelines fall behind with innovations in clinical practice. After the introduction of new treatment modalities some time passes before synthesized evidence finds its way into guideline recommendations. In the case of the novel oral anticoagulant drugs such as dabigatran and rivaroxaban this implementation into guidelines has been relatively swift.At this moment there is lack of day-to-day clinical experience with the newly introduced drugs and therefore clinical evidence is less unequivocal. Clinical practice usually differs from the setting of a clinical trial. Post surgical gastrointestinal upset and vomiting may reduce the effectiveness of oral antithrombotic therapy. To start prophylactic treatment post surgery with subcutaneous administered LMWH is therefore an attractive alternative.The choice of the authors for a combination treatment of two individually established safe and efficient therapeutic treatment modalities is understandable, but has a number of methodological shortcomings. Patient management was instituted without any preliminary studies, such as to identify the optimal, safe and effective, dosing strategy for the overlap of two different treatment modalities. In addition, a pragmatic, non-evidence based, choice was made for the single use of a low dose of 150 mg dabigatran once daily, irrespective of patient characteristics such as bodyweight, age or kidney function. On the other hand, all consecutive patients who met the inclusion criteria were managed according to the protocol, minimising selection bias. Data on complications such as VTE, bleeding, transfusion rates, periprocedural infections and mortality were prospectively collected and reviewed by an independent reviewer to control for bias.et al., comparable clinical experience was gained in the United States, in this case in the setting of a clinical study, with similar alternative treatment strategies, bridging the periprocedural period with LMWH and making the transition to oral anticoagulant treatment before hospital discharge [In parallel to the article by Subramanian ischarge . This stet al. article adds to our knowledge on the everyday use of the novel oral anticoagulant medication and shows that the choice of prophylactic treatment does depend on clinical circumstances but also on patient preference.The need for  data on the novel oral anticoagulant drugs derived from clinical practice is widely recognized. Despite methodological shortcomings, the recent Subramanian


Neuronal firing is intrinsically noisy, and as signals travel through nervous systems, the precision and reliability of the timing information is varied. At some processing stages spike timing precision is reduced through propagation; e.g., as in auditory signals transmitted from the brainstem to the inferior colliculus. On the other hand, timing information can be sharpened through propagation, as in transmission from the auditory nerve to the brainstem. Indeed, accurate coincidence detection is possible despite the inherent noise of the individual neurons. Motivated by this variability of timing information processing in the auditory system, we investigate how changes in the cellular and synaptic properties contribute to improved or decreased precision of spike timing through synaptic transmission.We use a three-dimensional conductance-based model based on Morris-Lecar equations with added voltage-sensitive potassium M-current. Parameters are tuned to represent dynamics of hippocampal pyramidal cells . The sinWe identify regions in parameter space where the spike timing precision can be explained by the distributions of order statistics of input times. In this region, precision is mostly independent of synaptic time constant and the input strength, provided the input is strong enough. Rather, it is most strongly affected by the number of incoming input lines. This dependence is similar for both coincidence detector and integrator models. In other parameter regimes, the spiking precision depends more subtly on details of interaction between the adaptation mechanism (in the form of M-current) and leak (or background) conductance. We use phase plane and bifurcation analysis to explain results of our numerical observations.


Aims. To examine the dental treatment needs of inner-city Vancouver elementary school-aged children and relate them to sociodemographic characteristics. Methods. A census sampling comprising 562 children from six out of eight eligible schools was chosen (response rate was 65.4%). Dental treatment needs were assessed based on criteria from the World Health Organization. Results. Every third child examined needed at least one restorative treatment. A higher proportion of children born outside Canada were in need of more extensive dental treatments such as pulp care and extractions compared to the children born in Canada. There were no statistically significant differences in dental treatment needs between age, gender, or income groups or between children with or without dental insurance (Chi Squared P > 0.05). The best significant predictors  of higher dental treatment needs were being born outside Canada, gender, time of last dental visit, and family income. Having dental insurance did not associate with needing less treatment. Conclusion. A high level of unmet dental treatment needs (32%) was found in inner-city Vancouver elementary school-aged children. Children born outside Canada, particularly the ones who recently arrived to Canada, needed more extensive dental treatments than children born in Canada. Dental caries has a negative impact on an individual's well-being and quality of life . It is cDental caries is one of the four most expensive diseases to treat . FinanciVancouver inner-city schools are found in areas with the lowest residential stability, highest housing density, and highest population diversity in terms of languages spoken and countries of birth . In VancThe aim of the present study was to examine dental treatment needs of a cohort of inner-city Vancouver elementary school-aged children and relate these treatment needs to a number of sociodemographic factors.The study was approved by the University of British Columbia Ethics Board (H11-00621) and by the Vancouver School Board. According to the socio-economic mapping provided by the Human Early Learning Partnership, Vancouver School District 39  encompasses one of the most disadvantaged areas in British Columbia, Canada . TherefoA census sampling was chosen to obtain an accurate overview of the dental treatment needs of all inner-city Vancouver elementary school-aged children, including the children from kindergarten to grade seven who at the time of the study attended the preselected schools. The recruitment of children was facilitated by school staff and by youth or social workers. A letter of initial contact for parents including a brief summary of the project was translated into the five most common languages according to the demographic profile of inner-city Vancouver. These documents were sent to the children's parents or guardians along with a consent form. The study protocol had been previously tested in a sample of 20 children from an inner-city elementary school not included in the eight schools selected for the present study. During the pilot study, feedback from the children and staff was sought. Subsequently, some revisions to the study's protocol were made. The data of the present study was collected from May 2011 to January 2012. A total of three attempts, including follow-up calls, were made to reach the parents and guardians of the children. The final response rate was 65.4%, and the final study sample included 562 children. Information about these children was collected by means of interview, structured questionnaire, and clinical examination. The sociodemographic data of each family's income, education, and dental insurance status was obtained from the Vancouver School Board. The study variables are presented in The clinical examination was done by a trained dentist who was assisted by another experienced dentist and included assessments of dental treatment needs based on the WHO criteria for Oral Health Surveys . The intAll analyses were performed employing SPSS 21.00 software. Univariate analyses were used to describe the children in terms of a number of socio-demographic factors and to test the data for normalcy in order to prepare for subsequent inferential bivariate and multivariate analyses. Bivariate analyses were employed to test associations between dental treatment needs and socio-demographic factors (Chi Squared test/Fisher's exact test). Linear multiple regression was used to study dental treatment need related outcomes  in relation to socio-demographic factors. The present study comprised a total of 562 children from kindergarten to grade seven, of which 56% were boys and 44% were girls. The sample distribution according to socio-demographic variables is presented in P = 0.024) when compared to the ones who had lived in Canada for a longer period of time.P < 0.001), and the best statistically significant predictors were gender, born outside Canada, and being from a family with a higher income. These predictors jointly explained 17% of the variation (adjusted R square = 0.169). The second multiple regression model for the “number of treatments needed” was also highly statistically significant (P < 0.001), and the best predictors were gender  and being born outside Canada . These two predictors jointly explained 22% of the variation in the total number of treatments needed (adjusted R square = 0.220).The present study focused on the overall dental treatment needs and the specific treatment modalities of unmet dental treatment needs of children from Vancouver's inner-city elementary schools. Prior to discussing the present study's results, it is important to acknowledge that only simple school-based dental examinations were employed, which may have led to an underestimation of the true extent of the dental treatment needs of this cohort of inner-city elementary school-aged children. Overall, a relatively high level of treatment needs was found, as every third child needed to be referred for dental treatments. This high proportion (32%) of Vancouver elementary school-aged children in need of operative treatments is higher than the record of 20% for Canadian population in need of dental treatments as reported in the National Canadian 2007–2009 Survey . Unmet tRecent immigrants to Canada are known to be at high risk of poverty, and it has been reported that this risk has significantly increased in recent years . The priIn a previous Canadian study, the strongest predictor for higher levels of untreated caries in immigrant children was a lack of dental insurance . HoweverTo address the problem of the relatively high level of unmet treatment needs observed in Vancouver inner-city elementary school-aged children, multiple strategies should be considered. For example, the newly formed Platform for Better Oral Health in Europe is working at a macrolevel by bringing interested associations, groups, and individuals together to alert national governments to oral health problems and to promote policies reducing disparities in oral health . AnotherThe unmet dental treatment needs were high in this cohort of Vancouver inner-city elementary school-aged children, and every third child needed an operative dental treatment. Higher treatment needs were found in children who had not visited a dentist within the last year and who had recently immigrated to Canada.


A growing body of evidence shows that mindfulness-based interventions reduce symptoms and improve health-related quality of life. Several instruments have been developed to measure mindfulness. To make a reasonable choice among these instruments, it is important to know the quality of each instrument. The objectives of this study were to critically assess and compare the measurement properties of the existing mindfulness instruments.Ovid Medline and Psycinfo were searched to identify relevant articles on the development and evaluation of the measurement properties of the mindfulness instruments. Using the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist, the methodological quality of the selected studies was evaluated. For each instrument, the measurement properties were separately assessed by two independent reviewers. Discrepancies were discussed with a third reviewer, and final scores were obtained based on the discussion.Our search strategy identified a total of 595 articles; 15 articles were selected. These articles showed the measurement properties of 11 different instruments. For the same instrument, the measurement properties were sometimes evaluated for different populations. Among the 11 instruments, the Mindful Attention Awareness Scale (MAAS) and the Kentucky Inventory of Mindfulness Skills (KIMS) were the most frequently evaluated.Study findings to date suggest that evidence of the psychometric quality of most mindfulness instruments is limited. Future studies investigating measurement properties are needed.