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Objective: 11C-Methionine positron emission tomography (MET-PET) is used for stereotactic radiotherapy planning in meningioma patients. The role of MET-PET during subsequent follow-up (FU) is unclear. We analyzed the uptake of 11C-Methionine before and after stereotactic radiotherapy (SRT) in patients with a complex meningioma and investigated if there was a difference between patients with progressive disease (PD) and stable disease (SD) during FU. Methods: This retrospective study investigates 62 MET-PETs in 29 complex meningioma patients. Standardized uptake value (SUV)max and SUVpeak tumor-to-normal ratios (T/N-ratios) were calculated, comparing the tumor region with both the mirroring intracranial area and the right frontal gray matter. The difference in 11C-Methionine uptake pre- and post-SRT was analyzed, as well as the change in uptake between PD or SD. Results: Median (IQR) FU duration was 67 months (50.5–91.0). The uptake of 11C-Methionine in meningiomas remained increased after SRT. Neither a statistically significant difference between MET-PETs before and after SRT was encountered, nor a significant difference in one of the four T/N-ratios between patients with SD versus PD with median (IQR) SUVmax T/NR front 2.65 (2.13–3.68) vs 2.97 (1.55–3.54) [p = 0.66]; SUVmax T/Nmirror 2.92 (2.19–3.71) vs 2.95 (1.74–3.60) [p = 0.61]; SUVpeak T/NR front 2.35 (1.64–3.40) vs 2.25 (1.44–3.74) [p = 0.80]; SUVpeak T/Nmirror 2.38 (1.91–3.36) vs 2.35 (1.56–3.72) [p = 0.95]. Conclusions: Our data do not support use of MET-PET during FU of complex intracranial meningiomas after SRT. MET-PET could not differentiate between progressive or stable disease. [ABSTRACT FROM AUTHOR]

Background: Transcranial Doppler (TCD) is a technique to assess blood flow velocity in the cerebral arteries. TCD is frequently used to monitor aneurysmal subarachnoid hemorrhage (aSAH) patients. This study compares TCD-criteria for vasospasm and its association with Delayed Cerebral Ischemia (DCI). An overall score based on flow velocities of various intracranial arteries was developed and evaluated. Methods: A retrospective diagnostic accuracy study was conducted between 1998 and 2017 with 621 patients included. Mean flow velocity (MFV) of the cerebral artery was measured between 2–5 days and between 6–9 days after ictus. Cutoff values from the literature, new cutoff values, and a new composite score (Combined Severity Score) were used to predict DCI. Sensitivity, specificity, and area under the curve (AUC) were determined, and logistic regression analysis was performed. Results: The Combined Severity Score showed an AUC 0.64 (95%CI 0.56-.71) at days 2–5, with sensitivity 0.53 and specificity 0.74. The Combined Severity Score had an adjusted Odds Ratio of 3.41 (95CI 1.86–6.32) for DCI. MCA-measurements yielded the highest AUC to detect DCI at day 2–5: AUC 0.65 (95%CI 0.58–0.73). Optimal cutoff MFV of 83 cm/s for MCA resulted in sensitivity 0.73 and specificity 0.50 at days 2–5. Conclusion: TCD-monitoring of aSAH patients may be a valuable strategy for DCI risk stratification. Lower cutoff values can be used in the early phase after the ictus (day 2–5) than are commonly used now. The Combined Severity Score incorporating all major cerebral arteries may provide a meaningful contribution to interpreting TCD measurements. [ABSTRACT FROM AUTHOR]

Purpose: While hearing loss is a well-known condition following microvascular decompression (MVD) for hemifacial spasm (HFS), tinnitus is an underreported one. This study aims to identify prevalence, characteristics, severity, and predictors of tinnitus following MVD for HFS. Methods: A single-center cohort of 55 HFS patients completed a questionnaire approximately 5 years following MVD. Data encompassed tinnitus presence, side, type, onset, and severity measured by a 10-point Visual Analogue Scale (VAS). Descriptive, correlation, and logistic regression analyses were conducted. Results : At surgery, participants' median age was 58 years (IQR 52–65). The median duration of HFS symptoms before surgery was 5 years (IQR 3–8), slightly predominant on the left (60%). Postoperative tinnitus was reported by 20 patients (36%), versus nine (16%) that reported preoperative tinnitus. Postoperative tinnitus was ipsilateral on the surgical side in 13 patients (65%), bilateral in six (30%), and contralateral in one (5%). Among patients with bilateral postoperative tinnitus, 33% did not have this preoperatively. Tinnitus was continuous in 70% of cases and pulsatile in 30%. Onset of new tinnitus was in 58% immediately or within days, in 25% within three months, and in 17% between three months and one year after surgery. The mean severity of postoperative tinnitus was 5.1 points on the VAS. Preoperative tinnitus and presence of arachnoid adhesions had suggestive associations with postoperative tinnitus in initial analyses (p = 0.005 and p = 0.065). However, preoperative tinnitus was the only significant predictor of postoperative tinnitus (p = 0.011). Conclusion: Tinnitus is a common condition following MVD for HFS, with a moderate overall severity. Causes behind postoperative tinnitus remain obscure but could be related to those of postoperative hearing loss in this patient population. Clinicians should be aware of tinnitus following MVD and vigilantly monitor its occurrence, to facilitate prevention efforts and optimize outcome for HFS patients undergoing MVD. [ABSTRACT FROM AUTHOR]

This article discusses a case report of a 67-year-old woman with Parkinson's disease who experienced episodes of reduced responsiveness. These spells occurred after taking her first dose of levodopa and could last up to one hour. The article explains that these episodes were attributed to orthostatic hypotension, a condition where blood pressure drops when standing up. The patient was advised to drink ample water after waking up and postpone taking levodopa until after breakfast, which successfully eliminated the episodes. The article also discusses the "hypotensive twilight zone," a state of impaired consciousness caused by cerebral hypoperfusion, which can occur in orthostatic hypotension. The authors emphasize the importance of recognizing and properly diagnosing these episodes to prevent unnecessary disability and avoid increasing medication doses. [Extracted from the article]

Tremor, bradykinesia, and rigidity are incapacitating motor symptoms that can be suppressed with stereotactic neurosurgical treatment like deep brain stimulation (DBS) and ablative surgery (e.g., thalamotomy, pallidotomy). Traditionally, clinicians rely on clinical rating scales for intraoperative evaluation of these motor symptoms during awake stereotactic neurosurgery. However, these clinical scales have a relatively high inter-rater variability and rely on experienced raters. Therefore, objective registration (e.g., using movement sensors) is a reasonable extension for intraoperative assessment of tremor, bradykinesia, and rigidity. The main goal of this scoping review is to provide an overview of electronic motor measurements during awake stereotactic neurosurgery. The protocol was based on the PRISMA extension for scoping reviews. After a systematic database search (PubMed, Embase, and Web of Science), articles were screened for relevance. Hundred-and-three articles were subject to detailed screening. Key clinical and technical information was extracted. The inclusion criteria encompassed use of electronic motor measurements during stereotactic neurosurgery performed under local anesthesia. Twenty-three articles were included. These studies had various objectives, including correlating sensor-based outcome measures to clinical scores, identifying optimal DBS electrode positions, and translating clinical assessments to objective assessments. The studies were highly heterogeneous in device choice, sensor location, measurement protocol, design, outcome measures, and data analysis. This review shows that intraoperative quantification of motor symptoms is still limited by variable signal analysis techniques and lacking standardized measurement protocols. However, electronic motor measurements can complement visual evaluations and provide objective confirmation of correct placement of the DBS electrode and/or lesioning. On the long term, this might benefit patient outcomes and provide reliable outcome measures in scientific research. [ABSTRACT FROM AUTHOR]

This letter, published in the journal Clinical Autonomic Research, discusses the clinical signs of the transition from syncope (fainting) to hypoxic coma (a state of reduced oxygen supply to the brain). The authors describe a case report of a 45-year-old woman who experienced episodes of unconsciousness, and they provide a detailed analysis of videos taken during these episodes. The videos show distinct phases of unconsciousness, including severe hypoperfusion (reduced blood flow to the brain), loss of brainstem function, and subsequent recovery. The authors highlight the importance of recognizing these motor signs in order to differentiate syncope from other causes of loss of consciousness. [Extracted from the article]

Sown field margins can improve the conservation of biodiversity in rural areas and can contribute to the aesthetics of rural landscapes, thereby potentially increasing public support for agri-environmental measures. However, these two functions do not necessarily coincide. This raises the question whether field margins that are appreciated for their contribution to landscape aesthetics also deliver on the conservation of biodiversity. We conducted choice experiments with different groups of citizens and collected biodiversity data in the Netherlands, to investigate if the number of colors and vegetation cover in field margins increased respondents' appreciation for them, and how these visual cues correlated with taxonomic diversity and abundance of plants and invertebrates in those field margins. Using manipulated photos, we also assessed whether the presence of colorful field margins in a range of different rural landscapes increased respondents' appreciation of those landscapes. Respondents preferred colorful margins with high vegetation cover and showed a preference for green rural landscapes with colorful field margins. The presence of colorful field margins increased landscape aesthetics most in the least appreciated landscapes. The number of colors correlated positively with the diversity of sown and spontaneous plant species, and overall invertebrate abundance and abundance of predatory invertebrates, but was not related to invertebrate diversity. Our results show for the first time that colorful field margins support both public appreciation and diversity of plants and abundance of ground-dwelling invertebrates, with potential advantages to farmers in terms of natural pest control, at least in intensively used agricultural landscapes. However, management practices to maintain a high number of colors over time may be detrimental for invertebrate diversity. To optimize the different functions, we recommend that field margin layouts should consist of a perennial part that is allowed to develop over time, in combination with a part that is managed for its colorfulness. [ABSTRACT FROM AUTHOR]

Purpose: We compared hemodynamic parameters between subjects with marked, intermediate and minimal cardioinhibition during vasovagal syncope. Methods: The study included subjects with a decrease in heart rate while experiencing a complete vasovagal syncope during tilt-table testing. The subjects were classified as having marked, intermediate or minimal cardioinhibition, based on tertile values of the decrease in heart rate. Hemodynamic parameters between these groups were compared before tilt in the supine position, shortly after tilt and during cardioinhibition. Results: A total of 149 subjects with a median age of 43 (interquartile range 24–60) years were included in the study. Among the three groups with different levels of cardioinhibition, the highest heart rate was observed in subjects with marked cardioinhibition both before and shortly after tilt and at the start of cardioinhibition. The heart rate decrease in these subjects was both larger and faster compared to subjects with minimal and intermediate cardioinhibition. Conclusion: Subjects with marked cardioinhibition have both a larger and faster decrease in heart rate compared to subjects with intermediate and minimal cardioinhibition, as early as from the start of cardioinhibition. Marked cardioinhibition is related to differences in hemodynamic profiles already present well before the start of cardioinhibition. [ABSTRACT FROM AUTHOR]

This paper aims to improve the diagnosis of syncope and transient loss of consciousness (TLOC) in children. Diagnostic problems stem, first, from some causes spanning various disciplines, e.g. cardiology, neurology and psychiatry, while the most common cause, vasovagal syncope, is not embraced by any specialty. Second, clinical variability is huge with overlapping signs and symptoms. Third, the approach to TLOC/syncope of the European Society of Cardiology (ESC) is underused in childcare. We explain the ESC guidelines using an additional paediatric literature review. Classification of TLOC and syncope is hierarchic and based on history taking. Loss of consciousness (LOC) is defined using three features: abnormal motor control including falling, reduced responsiveness and amnesia. Adding a < 5 min duration and spontaneous recovery defines TLOC. TLOC simplifies diagnosis by excluding long LOC (e.g. some trauma, intoxications and hypoglycaemia) and focussing on syncope, tonic–clonic seizures and functional TLOC. Syncope, i.e. TLOC due to cerebral hypoperfusion, is divided into reflex syncope (mostly vasovagal), orthostatic hypotension (mostly initial orthostatic hypotension in adolescents) and cardiac syncope (arrhythmias and structural cardiac disorders). The initial investigation comprises history taking, physical examination and ECG; the value of orthostatic blood pressure measurement is unproven in children but probably low. When this fails to yield a diagnosis, cardiac risk factors are assessed; important clues are supine syncope, syncope during exercise, early death in relatives and ECG abnormalities. Conclusions: In adults, the application of the ESC guidelines reduced the number of absent diagnoses and costs; we hope this also holds for children. What is Known: • Syncope and its mimics are very common in childhood, as they are at other ages. • Syncope and its mimics provide considerable diagnostic challenges. What is New: • Application of the hierarchic framework of transient loss of consciousness (TLOC) simplifies diagnosis. • The framework stresses history-taking to diagnose common conditions while keeping an eye on cardiac danger signs. [ABSTRACT FROM AUTHOR]

Purpose: In preventing Chronic Postoperative Inguinal Pain (CPIP) after inguinal herniorrhaphy, mesh position and mesh fixation seem important factors. The SOFTGRIP trial compared the TransInguinal PrePeritoneal (TIPP) repair to Polysoft mesh, to the Open anterior repair (Lichtenstein) using the self-gripping ProGrip mesh. Since CPIP might resolve and recurrence rate increase, this study reports the SOFTGRIP trial's long-term results (with a minimal follow-up of 5 years). Methods: All patients initially randomized in the SOFTGRIP trial were contacted if not deceased. Patients were invited for an interview and physical examination. The procedures and methodology of this randomized clinical trial have been published together with the short-term results. The main outcomes for this long-term follow-up study were chronic pain, recurrences, re-operations and numbness. Results: A total of 193 patients (81.4% of the initially randomized patients) were included for long-term follow-up analyses, 96 after TIPP, 97 after ProGrip Lichtenstein. After a median follow-up of 74 months (range 60–80) there were no significant differences between the two groups. Overall, chronic pain drastically decreased. Fourteen patients reported CPIP at long-term follow-up (overall 7.3%, 7 after TIPP and 7 after ProGrip Lichtenstein, any form, frequency and intensity of pain included). Recurrence rate increased from 2.6% (n = 6) at one-year follow-up, to 8.3% (n = 16) at 5-year's follow-up. Conclusion: The SOFTGRIP trial´s long-term outcomes show that after both TIPP and ProGrip Lichtenstein, recurrence rate increases and CPIP mostly disappears. These findings aid in better informing patients on the benefits and harms of inguinal hernia repair. The findings of accumulating recurrences and fading of chronic pain, confirms the need for long-term follow-up studies. High-quality long-term data on TIPP, ProGrip Lichtenstein and other types of herniorrhaphy are scarce and complication rates vary widely. Further long-term studies are needed to reveal the true spectrum of benefits and harms of the different inguinal hernia repair techniques. Trial registration: Registered on August 25, 2009 at the Dutch Trial Registry (www.trialregister.nl) NTR1853. [ABSTRACT FROM AUTHOR]

Differentiation of pituitary neuroendocrine tumor (PitNET) tissue from surrounding normal tissue during surgery is challenging. A number of fluorescent agents is available for visualization of tissue discrepancy, with the potential of improving total tumor resection. This review evaluates the availability, clinical and technical applicability of the various fluorescent agents within the field of pituitary surgery. According to PRISMA guidelines, a systematic review was performed to identify reports describing results of in vivo application of fluorescent agents. In this review, 15 publications were included. Sodium Fluorescein (FNa) was considered in two studies. The first study reported noticeable fluorescence in adenoma tissue, the second demonstrated the strongest fluorescence in non-functioning pituitary adenomas. 5-Aminolevulinic acid (5-ALA) was investigated in three studies. One study compared laser-based optical biopsy system (OBS) with photo-diagnostic filter (PD) and found that the OBS was able to detect all microadenomas, even when MRI was negative. The second study retrospectively analyzed twelve pituitary adenomas and found only one positive for fluorescence. The third investigated fifteen pituitary adenomas of which one displayed vague fluorescence. Indocyanine green (ICG) was researched in four studies with variable results. Second-Window ICG yielded no significant difference between functioning and non-functioning adenomas in one study, while a second study displayed 4 times higher fluorescence in tumor tissue than in normal tissue. In three studies, OTL38 showed potential in non-functioning pituitary adenomas. At present, evidence for fluorescent agents to benefit total resection of PitNETs is lacking. OTL38 can potentially serve as a selective fluorescent agent in non-functioning pituitary adenomas in the near future. [ABSTRACT FROM AUTHOR]

Background and objectives: The modified Rankin Scale (mRS) is one of the most frequently used outcome measures in trials in patients with an aneurysmal subarachnoid hemorrhage (aSAH). The assessment method of the mRS is often not clearly described in trials, while the method used might influence the mRS score. The aim of this study is to evaluate the inter-method reliability of different assessment methods of the mRS. Methods: This is a prospective, randomized, multicenter study with follow-up at 6 weeks and 6 months. Patients aged ≥ 18 years with aSAH were randomized to either a structured interview or a self-assessment of the mRS. Patients were seen by a physician who assigned an mRS score, followed by either the structured interview or the self-assessment. Inter-method reliability was assessed with the quadratic weighted kappa score and percentage of agreement. Assessment of feasibility of the self-assessment was done by a feasibility questionnaire. Results: The quadratic weighted kappa was 0.60 between the assessment of the physician and structured interview and 0.56 between assessment of the physician and self-assessment. Percentage agreement was, respectively, 50.8 and 19.6%. The assessment of the mRS through a structured interview and by self-assessment resulted in systematically higher mRS scores than the mRS scored by the physician. Self-assessment of the mRS was proven feasible. Discussion: The mRS scores obtained with different assessment methods differ significantly. The agreement between the scores is low, although the reliability between the assessment methods is good. This should be considered when using the mRS in clinical trials. Trial registration: www.trialregister.nl; Unique identifier: NL7859. [ABSTRACT FROM AUTHOR]

Purpose: Radiologic follow-up of patients with a meningioma at the skull base or near the venous sinuses with magnetic resonance imaging (MRI) after stereotactic radiotherapy (SRT) and neurosurgical resection(s) can be difficult to interpret. This study evaluates the addition of 11C-methionine positron emission tomography (MET-PET) to the regular MRI follow-up. Methods: This prospective pilot study included patients with predominantly WHO grade I meningiomas at the skull base or near large vascular structures. Previous SRT was part of their oncological treatment. A MET-PET in adjunct to their regular MRI follow-up was performed. The standardized uptake value (SUV) was determined for the tumor and the healthy brain, on the pre-SRT target delineation MET-PET and the follow-up MET-PET. Tumor-to-normal ratios were calculated, and 11C-methionine uptake over time was analyzed. Agreement between the combined MRI/MET-PET report and the MRI-only report was determined using Cohen's κ. Results: Twenty patients with stable disease underwent an additional MET-PET, with a median follow-up of 84 months after SRT. Post-SRT SUV T/N ratios ranged between 2.16 and 3.17. When comparing the pre-SRT and the post-SRT MET-PET, five categories of SUV T/N ratios did not change significantly. Only the SUVpeak T/Ncortex decreased significantly from 2.57 (SD 1.02) to 2.20 (SD 0.87) [p = 0.004]. A κ of 0.77 was found, when comparing the MRI/MET-PET report to the MRI-only report, indicating no major change in interpretation of follow-up data. Conclusion: In this pilot study, 11C-methionine uptake remained remarkably high in meningiomas with long-term follow-up after SRT. Adding MET-PET to the regular MRI follow-up had no impact on the interpretation of follow-up imaging. [ABSTRACT FROM AUTHOR]

An expert committee was formed to reach consensus on the use of tilt table testing (TTT) in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when other provocative cardiovascular autonomic tests are needed. While TTT adds to history taking, it cannot be a substitute for it. An abnormal TTT result is most meaningful if the provoked event is recognised by patients or eyewitnesses as similar to spontaneous events. The minimum requirements to perform TTT are a tilt table, a continuous beat-to-beat blood pressure monitor, at least one ECG lead, protocols for the indications stated below and trained staff. This basic equipment lends itself to the performance of (1) additional provocation tests, such as the active standing test, carotid sinus massage and autonomic function tests; (2) additional measurements, such as video, EEG, transcranial Doppler, NIRS, end-tidal CO2 or neuro-endocrine tests; and (3) tailor-made provocation procedures in those with a specific and consistent trigger of TLOC. TTT and other provocative cardiovascular autonomic tests are indicated if the initial evaluation does not yield a definite or highly likely diagnosis, but raises a suspicion of (1) reflex syncope, (2) the three forms of orthostatic hypotension (OH), i.e. initial, classic and delayed OH, as well as delayed orthostatic blood pressure recovery, (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT is to teach patients with reflex syncope and OH to recognise hypotensive symptoms and to perform physical counter manoeuvres. [ABSTRACT FROM AUTHOR]

Purpose: Our aim was to develop and validate a machine learning (ML)-based approach for interpretation of I-123 FP-CIT SPECT scans to discriminate Parkinson's disease (PD) from non-PD and to determine its generalizability and clinical value in two centers. Methods: We retrospectively included 210 consecutive patients who underwent I-123 FP-CIT SPECT imaging and had a clinically confirmed diagnosis. Linear support vector machine (SVM) was used to build a classification model to discriminate PD from non-PD based on I-123-FP-CIT striatal uptake ratios, age and gender of 90 patients. The model was validated on unseen data from the same center where the model was developed (n = 40) and consecutively on data from a different center (n = 80). Prediction performance was assessed and compared to the scan interpretation by expert physicians. Results: Testing the derived SVM model on the unseen dataset (n = 40) from the same center resulted in an accuracy of 95.0%, sensitivity of 96.0% and specificity of 93.3%. This was identical to the classification accuracy of nuclear medicine physicians. The model was generalizable towards the other center as prediction performance did not differ thereby obtaining an accuracy of 82.5%, sensitivity of 88.5% and specificity of 71.4% (p = NS). This was comparable to that of nuclear medicine physicians (p = NS). Conclusion: ML-based interpretation of I-123-FP-CIT scans results in accurate discrimination of PD from non-PD similar to visual assessment in both centers. The derived SVM model is therefore generalizable towards centers using comparable acquisition and image processing methods and implementation as diagnostic aid in clinical practice is encouraged. [ABSTRACT FROM AUTHOR]

Purpose: Vasovagal syncope (VVS) affects more women than men. We determined whether this sex ratio affects tilt table test (TTT) results. Methods: We retrospectively studied TTT outcomes in suspected VVS. TTT consisted of supine rest, a maximum 20 min of head-up tilt without and, if nitroglycerin was needed, a further maximum 20 min after nitroglycerin administration. TTT was terminated if VVS occurred. We used binary logistic regression for the entire TTT and for each phase, with VVS as outcome and age and sex as predictors. Results: TTT provoked vasovagal (pre)syncope in 494 out of 766 tests (64%). The proportion of men and women who fainted during the entire TTT did not differ significantly between the sexes (p = 0.13, corrected for age). A lower proportion of women than men had VVS in the phase without nitroglycerin (odds ratio 0.54; 95% confidence interval 0.37–0.79; p = 0.002, corrected for age), whereas a higher proportion of women than men fainted after nitroglycerin (odds ratio 1.58; 95% confidence interval 1.13–2.21; p = 0.008, corrected for age). These sex differences remained significant after correction for a history of orthostatic versus emotional triggers. The effect of sex on TTT outcome was closely associated with differences of blood pressure change upon tilt-up (lower in men in both TTT phases: without nitroglycerin p = 0.003; with nitroglycerin p = 0.05), but not with heart rate changes. Conclusion: Men were more susceptible to induction of VVS without nitroglycerin and women after it. The unexpected findings may be due to sex-specific pathophysiological differences. [ABSTRACT FROM AUTHOR]

Binge eating disorder (BED), with its compulsive and addictive components, may often underlie weight regain after gastrointestinal bariatric surgeries. BED is therefore considered an exclusion criterion for these surgeries. Anecdotal reports suggest that deep brain stimulation (DBS) is an effective treatment for addictive disorders with, similar to BED, pathological changes in cerebral reward circuitry. We therefore assessed effect of DBS of the nucleus accumbens (NAC) in a rat model of BED. Twenty-one male obesity prone Wistar rats with DBS electrodes placed in NAC subregions were subjected to a binge eating protocol. Binge eating was significantly reduced with DBS during (NAC core) or before (NAC lateral shell) the binge. These outcomes provide a base to further explore the potential of DBS in the treatment of BED. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) are recommended by several scientific societies as first-line therapy for the prevention of stroke and systemic embolism in patients with atrial fibrillation. However, there is uncertainty regarding the organisation of anticoagulation care, with various caregivers being involved. Patients and caregivers are often confronted by uncertainty about the coordination of treatment. With the functional resonance analysis method we visualised the process of anticoagulation care in daily practice in the Maastricht region. This resulted in recommendations on how to improve the organisation of anticoagulation care for DOAC patients. [ABSTRACT FROM AUTHOR]

Purpose: Guidelines propose different rest–stress activity ratios (RSAR) for one-day stress-first SPECT myocardial perfusion imaging (MPI), but evidence is limited. Our aim was to determine and validate the minimal RSAR resulting in the same diagnostic outcome in one-day stress-first SPECT MPI. Methods: Forty-seven patients referred for rest after stress CZT-SPECT/CT MPI were prospectively included. Rest acquisitions were performed 3 h after stress. In addition to the stress and rest acquisitions, the first 22 patients underwent an additional acquisition prior to the rest injection to determine the remaining stress activity. Next, we simulated six RSARs varying from 1.0 to 3.5 in both patients and a phantom and compared the images to those using the reference RSAR of 4.0. Differences in summed difference score (SDS) >2 or ischemic defect interpretation were considered to significantly influence diagnostic outcome. After deriving the minimal RSAR, it was validated in 25 additional patients by comparing it to a RSAR of 4.0. Results: After 3 h only 26% of the stress activity was still present in the myocardium. SDS differences >2 were found in one (4%) patient using RSAR of 3.5, 2.5 and 2.0, in three (12%) using 1.5 and in five (20%) using SRAR of 1.0. These results were consistent with the phantom study showing SDS differences >2 for RSARs ≤1.5 and with the visual interpretation which showed an increased number of deviating scans for RSAR 1.0. Validating the RSAR of 2.0 resulted in a different SDS in one patient (SDS of 30 versus 11). Moreover, two scans were interpreted as ischemic instead of normal when using RSAR 2.0 and in two other scans the opposite was the case. Conclusions: A RSAR of 2.0 in one-day stress-first MPI SPECT seems sufficient to obtain accurate diagnostic outcomes and is therefore recommended to reduce radiation exposure. [ABSTRACT FROM AUTHOR]

Background: Position of the mesh and the method of fixation are important in the occurrence of chronic pain in inguinal herniorrhaphy. An RCT was conducted to evaluate chronic pain after transinguinal preperitoneal (TIPP) repair compared with a Lichtenstein-like repair with a semi-resorbable self-fixing mesh (ProGrip).Methods: Patients with a primary unilateral inguinal hernia were randomized either to the TIPP (PolySoft mesh) or to repair with a ProGrip mesh. Primary objective was the occurrence of chronic pain after surgery. Secondary objectives were, i.e., recurrences, complications, and quality of life. Follow-up occurred after 2 weeks, 3 months, and 1 year. Patients and physicians were blinded.Results: Two hundred and fifty-eight patients were randomized to TIPP or ProGrip mesh repair. Two hundred and thirty-eight were included in the analysis: 122 in the TIPP group and 116 in the ProGrip group. Baseline characteristics were compatible. After 2 weeks and 3 months, there was significantly more moderate and severe pain in the ProGrip group on different pain scores. Median pain scores were very low in both groups after 3 months and 1 year (0-0.5 on a scale of 0-10). There was no difference in pain scores between both groups after 1 year. Recurrence rates were low; three patients in each group (2.6 % ProGrip and 2.5 % TIPP).Conclusion: There was no significant difference in chronic pain between the inguinal repairs with the use of a ProGrip mesh compared with a TIPP repair at 1 year after surgery. In both groups, the occurrence of chronic pain was low. [ABSTRACT FROM AUTHOR]

A novel method to assess left ventricular (LV) mechanical dyssynchrony using three-dimensional echocardiography (3DE) and semi-automated border detection was investigated, which might be superior in prediction of response to cardiac resynchronisation therapy (CRT) compared to traditional measures that rely solely on segmental time-to-contraction. Twenty-eight heart failure patients underwent real-time 3DE before CRT and at 6–12 months follow-up. Analysis of 3DE was performed using TomTec Research-Arena software featuring semi-automated endocardial border detection. The following echocardiographic parameters were calculated in a 16-segment model: areas under segmental time-volume-curves (STV); delay between contraction of the earliest and latest segment (L-E); and standard deviation of segmental time-to-contraction (SDI). Response to CRT was defined as ≥10% decrease in LV end-systolic volume at follow-up. Baseline Pre-STV had a higher sensitivity than SDI for prediction of response (94 vs 67%, respectively), with equal specificity (78%) and a higher area under receiver operator characteristic curve. In contrast, L-E had a sensitivity of 83% and a specificity of 56%. Using 3DE, methods that combine segmental time-to-contraction with segmental contractility might improve LV dyssynchrony assessment compared to traditional methods based on segmental time-to-contraction alone. Pre-STV might be a better predictor of response to CRT than SDI. [ABSTRACT FROM AUTHOR]

To derive and validate a practical patient-specific dose protocol to obtain an image quality, expressed by the image noise, independent of patients' size and a better radiation dose justification in coronary CT angiography (CCTA) using prospective ECG triggering. 43 patients underwent clinically indicated CCTA. The image noise, defined as the standard deviation of pixel attenuation values in a homogeneous region in the liver, was determined in all scans. Subsequently, this noise was normalized to the radiation exposure. Next, three patient-specific parameters, body weight, body mass index and mass per length (MPL), were tested for the best correlation with normalized image noise. From these data, a new dose protocol to provide a less variable image noise was derived and subsequently validated in 84 new patients. The normalized image noise increased for heavier patients for all patients' specific parameters (p < 0.001). MPL correlated best with the normalized image noise and was selected for dose protocol optimization. This new protocol resulted in image noise levels independent of patients' MPL (p = 0.28). A practical method to obtain CCTA images with noise levels independent of patients' MPL was derived and validated. It results in a less variable image quality and better radiation exposure justification and can also be used for CT scanners from other vendors. [ABSTRACT FROM AUTHOR]

Background: Cerebral autoregulation is increasingly recognized as a factor that requires evaluation when managing poor grade aneurysmal subarachnoidal hemorrhage (aSAH) patients. In this single center pilot study, we investigated whether intraventricular intracranial pressure (ICP) derived when extraventricular drain (EVD) is open can be used to calculate dynamic autoregulation estimates in ICU aSAH patients.Methods: Ten patients with the diagnosis of aSAH as confirmed by computed tomography (CT) and CT-angiography were enrolled. ICP was monitored via a transducer connected to the most proximal side exit of the EVD catheter. From at least 30 min periods of brain monitoring before, during, and after temporarily EVD closure, commonly used indexes of dynamic cerebral autoregulation were calculated.Results: Preserved pulsatile ICP signals were seen with open EVD. There were no significant changes in parameters describing cerebral autoregulation between EVD open and closed conditions. Power spectra of ABP and ICP showed no significant changes for the selected frequency ranges. There was a small significant increase in absolute ICP [2.4 (3.8) mmHg, p < 0.001] upon short-term EVD closure. Cerebral spinal reserve capacity (RAP index) worsened significantly by short-term EVD closure.Conclusions: Due to preserved slow fluctuations in the ICP signal, an open EVD system can be used to calculate dynamic autoregulation indices in aSAH patients requiring intensive care monitoring with the pressure measurement from the most proximal part of drain. If these results are confirmed in larger study, this technique can open the way for investigating the role of autoregulation disturbance in aSAH patients. [ABSTRACT FROM AUTHOR]

The MLL-AF9 fusion gene is associated with aggressive leukemias of both the myeloid and lymphoid lineage in infants, whereas in adults, this translocation is mainly associated with acute myeloid leukemia. These observations suggest that differences exist between fetal and adult tissues in terms of the 'cell of origin' from which the leukemia develops. Here we show that depending on extrinsic cues, human neonatal CD34+ cells are readily immortalized along either the myeloid or lymphoid lineage upon MLL-AF9 expression and give rise to mainly lymphoid leukemia in immunocompromised mice. In contrast, immortalization of adult bone marrow CD34+ cells is more difficult to achieve and is myeloid-biased, even when MLL-AF9 is expressed in purified hematopoietic stem cells (HSCs). Transcriptome analysis identified enrichment of HSC but not progenitor gene signatures in MLL-AF9-expressing cells. Although not observed in adult cells, neonatal cells expressing MLL-AF9 were enriched for gene signatures associated with poor prognosis, resistance to chemotherapeutic agents and MYC signaling. These results indicate that neonatal cells are inherently more prone to MLL-AF9-mediated immortalization than adult cells and suggest that intrinsic properties of the cell of origin, in addition to extrinsic cues, dictate lineage of the immortalized cell. [ABSTRACT FROM AUTHOR]

Objectives: In achondroplastic patients with slight complaints of medullary compression the cervical spinal cord regularly exhibits an intramedullary (CHII) lesion just below the craniocervical junction with no signs of focal compression on the cord. Currently, the prevalence of the lesion in the general achondroplastic population is studied and its origin is explored.Methods: Eighteen achondroplastic volunteers with merely no clinical signs of medullary compression were subjected to dynamic magnetic resonance imaging (MRI). The presence of a CHII lesion and craniocervical medullary compression in flexed and retroflexed craniocervical positions was explored. Several morphological characteristics of the craniocervical junction, possibly related to compression on the cord, were assessed.Results: A CHII lesion was observed in 39% of the subjects and in only one of these was compression at the craniocervical junction present. Consequently, no correlation between the CHII lesion and compression could be established. None of the morphological characteristics demonstrated a correlation with the CHII lesion, except thinning of the cord at the site of the CHII lesion.Conclusions: CHII lesions are a frequent finding in achondroplasia, and are generally unaccompanied by clinical symptoms or compression on the cord. Further research focusing on the origin of CHII lesions and their clinical implications is warranted.Key Points: • MRI now reveals exquisite detail of the cervical spinal cord. • Cervical cord lesions are observed in one third of the achondroplastic population. • These lesions yield high signal intensity on T2 weighted MRI. • They are generally unaccompanied by clinical symptoms or cord compression. • Their aetiology is unclear and seems to be unrelated to mechanical causes. [ABSTRACT FROM AUTHOR]

It has been shown that transcutaneous electrical neurostimulation (TENS) reduces sympathetic tone. Spinal cord stimulation (SCS) has proven qualities to improve coronary, peripheral, and cerebral blood circulation. Therefore, we postulate that TENS and SCS affect the autonomic nervous system in analogous ways. In this line of thought, cervical application of TENS might be a useful and simple adjunct in the treatment of cerebrovascular disease by improving cerebral blood flow. Experiments were performed in order to assess whether cervical TENS is safe and whether an effect on cerebral blood flow velocity (CBFV) can be shown in healthy subjects. A controlled, non-randomized, phase 1 study was performed with 20 healthy volunteers. Cervical TENS was applied in several frequencies, with and without hyperventilation. Continuous registration of blood pressure, pulse, CBFV (estimated by transcranial Doppler sonography) and end-tidal carbon dioxide concentration was performed. Cervical TENS was well-tolerated by all subjects. Despite small effects on heart rate (HR) and mean arterial blood pressure (MAP), a significant effect on middle cerebral artery (MCA) blood flow velocity was not demonstrated. No effect of age, gender, current or session order on MCA, HR, or MAP was found. TENS did not influence the effect of hyperventilation. In these experiments, application of cervical TENS is proven to be a safe procedure. However, no effects on cerebral blood flow velocity could be detected, perhaps due to the intact cerebral autoregulation in the healthy volunteers. [ABSTRACT FROM AUTHOR]

In autonomic failure (AF), blood pressure (BP) falls upon standing which is commonly ascribed to defective vasoconstriction and excessive pooling. Observations on the amount of pooling in AF are contradictory. We evaluated pooling using strain-gauge plethysmography (SGP) during head-up tilt (HUT) with a parachute harness fixed to the tilt table to avoid muscle tension in the lower limbs and thus to maximise pooling. 23 healthy subjects and 12 patients with AF were tilted for 5 min. BP and calf volume changes, as measured by SGP, were measured continuously. Multiple regression analysis was used to examine the effect of AF on orthostatic fluid shifts after adjustment for potential confounders. Patients did not differ from controls with respect to the increase of calf volume after 5 min HUT. The acute (0–1 min) and the prolonged (1–5 min) phases of calf volume responses to HUT were also similar between patients and controls. No correlation was found between the degree of orthostatic hypotension and the orthostatic calf volume change in AF. In one patient an additional measurement was made before rising from bed in the early morning demonstrating a greater albeit small increase of calf volume upon HUT. Orthostatic fluid shifts at the level of the calf in AF are not augmented during the course of the day despite marked hypotension. However, a small increase of pooling may be expected when the patient first gets out of bed in the morning probably due to the absence of oedema. [ABSTRACT FROM AUTHOR]

In this practically oriented review, we will outline the clinical approach of patients with falls due to an impairment or loss of consciousness. Following a set of definitions, we describe the salient clinical features of disorders leading to such falls. Among falls caused by true loss of consciousness, we separate the clinical characteristics of syncopal falls (due to reflex syncope, hypovolemia, orthostatic hypotension or cardiac syncope) from falls due to other causes of transient unconsciousness, such as seizures. With respect to falls caused by an apparent loss of consciousness, we discuss the presentation of cataplexy, drop attacks, and psychogenic falls. Particular emphasis will be laid upon crucial features obtained by history taking for distinguishing between the various conditions that cause or mimic a transient loss of consciousness. [ABSTRACT FROM AUTHOR]

Injuries as a result of assaults with sharp object in small children are rare and data on them are scarce. The Red Cross War Memorial Children's Hospital is presently the only Children's Hospital in South Africa with a dedicated Level 1 trauma unit for children under the age of 13 years, and we have an annual trauma load of over 10,000 patients. A retrospective review was performed using the Data Base of the Child Accident Prevention Foundation of Southern Africa at the Red Cross War Memorial Children's Hospital in Cape Town. All children who were coded as an 'assault with sharp object' were included in this study. Five-hundred-and-fifty-one (551) patients were retrospectively reviewed, of which 373 (68%) were boys and 177 (32%) girls. The mean age of the children was 7 years. The majority of children (51%) sustained injuries at the head or neck region, 26% sustained an injury at the trunk and 26% at the extremities. The majority of children sustained minor injuries (62%), thirty-three (33%) moderate and 5% severe injuries. Three children died. The most commonly recorded object used in the assault was glass or (broken) bottles (33%) and knives (18%). Other objects recorded included sticks, stones, pens, pencils, scissors, machetes and nails. The majority of perpetrators were known to the child. Assaults with a sharp object in small children are relatively rare and represent only 0.328% of all paediatric trauma patients. Although rare, these injuries carry a significant morbidity and even mortality. The majority of injuries occurred at home. Prevention programmes, specifically targeting the caretakers, should be implemented to prevent these tragic injuries. [ABSTRACT FROM AUTHOR]

Versican plays a role in tumor cell proliferation and adhesion and may also regulate cell phenotype. Furthermore, it is one of the pivotal proteoglycans in mesenchymal condensation during prechondrogenesis. We have previously demonstrated accumulation of versican protein in myoepithelial-like spindle cell proliferations and myxoid tissues of complex and mixed mammary tumors of dogs. The objective of this study was to investigate whether the high expression of versican relates to prechondrogenesis in these tissues. Therefore, we aimed to identify cartilage markers, such as collagen type II and aggrecan both at mRNA and protein level in relation to versican. The neopitope of chondoitin-6-sulphate (3B3) known to be generated in developing cartilage has been investigated by immunohistochemisty and a panel of antibodies were used to characterize the phenotype of cells that are involved in cartilage formation. In addition, co-localization of versican with hyaluronan and link protein was studied. RT-PCR revealed upregulation of genes of versican, collagen type II and aggrecan in neoplastic tissues, especially in complex and mixed tumors. Immunohistochemistry showed the expression of cartilage biomarkers not only in the cartilagenous tissues of mixed tumors, but also in myoepitheliomas and in the myoepithelial-like cell proliferations and myxoid areas of complex and mixed tumors. The results show the cartilagenous differentiation of complex tumors and myoepitheliomas and indicate that the myxoid tissues and myoepithelial-like cell proliferations are the precursor tissues of the ectopic cartilage in mixed tumors. Furthermore, we suggest that cartilage formation in canine mammary tumors is a result of (myo)epithelial to mesenchymal transition. [ABSTRACT FROM AUTHOR]

Background Imprecise definitions of syncope and related conditions appear common in the medical literature. To investigate the scope of the problem we systematically searched for definitions in high-ranking medical journals. Methods Literature review of articles on `syncope', `neuro cardiogenic syncope','neurally mediated syncope', `ortho static intolerance', and `ortho static hypotension' with these keywords in the title, mainly published in the ten journals with the highest impact in the fields of cardiology, internal medicine, and neurology. Results Syncope, neuro- cardiogenic syncope, neurally mediated syncope, orthostatic intolerance, and orthostatic hypotension were defined in only 41 %, 34%, 26 %, 38 %, and 48 % of papers respectively. Definitions, when given, differed considerably among papers. Orthostatic hypotension was most frequently defined, with an increase in number and consistency of definitions after publication of a consensus in 1996. Conclusions Syncope and related conditions proved to be infrequently and inconsistently defined in current medical literature. The lack of consistent terminology is likely to harm medical education, research, and patient care. There is a strong need for a systematic terminology for syncope and related conditions. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the contribution of reciprocal inhibition to muscle tone by examining the transmission in the reciprocal inhibitory pathway in patients with a known defect in the glycine receptor. The study was performed in eight patients with hereditary hyperekplexia, six with the major form and two with the minor form of the disease. A mutation in the α1-subunit of the glycine receptor had been demonstrated in the patients with the major form, whereas no mutation was seen in the patients with the minor form. Disynaptic reciprocal inhibition, which is presumed to be mediated by glycine, was not seen in the patients with the major form of the disease, while it could be evoked in the patients with the minor form of the disease. Presynaptic inhibition, which is presumed to be mediated by GABA, was seen in both types of patients. It is concluded that the major form of hereditary hyperekplexia is associated with impaired transmission in glycinergic reciprocal inhibitory pathways. The findings demonstrate the importance of reciprocal inhibition for the muscle tone in man, and it is suggested that the impaired reciprocal inhibition seen in patients with a defect in the glycine receptor may contribute to the increased muscle stiffness that is observed in these patients. [ABSTRACT FROM AUTHOR]

The clinical balance tests presently used cannot predict falls in Parkinson's disease (PD), perhaps because they probe fairly isolated "components" of postural control. The Multiple Tasks Test (MTT) is a new balance test that simultaneously assesses multiple components of postural control. We investigated whether this MTT can detect postural abnormalities in PD patients. Fifty young controls (mean age 27.6 years), 20 elderly controls (mean age 62.5 years), and 20 PD patients (mean age 61.8 years, mean Hoehn and Yahr stage 2.2) participated. The MTT consisted of eight separate tasks of increasing complexity, which were executed sequentially. These tasks were composed of several motor components (standing up, walking, avoiding obstacles, touching the floor, turning around, and sitting down) and one cognitive component (answering serial questions). Four additional components included carrying an empty or loaded tray, wearing slippery shoes, and reduced illumination. All components within each task had to be performed simultaneously or directly sequentially. Errors were defined as Hesitations (slowed performance) or Blocks (complete cessation), which were scored separately for execution of the motor and cognitive components. Speed of performance was not stressed, but we did measure the time taken to complete all tasks. The complete MTT was performed by all subjects, except for a subgroup of seven patients and seven elderly controls who performed a shortened version, with only three of the eight sequential tasks (simple, intermediate, and most difficult). The number of subjects that produced Hesitations or Blocks for the motor components differed between the three groups [two-way repeated measures MANOVA, F(2,7)=20.56; P<0.001], patients making more errors than young and elderly controls. Furthermore, the number of subjects that made motor errors increased as the tasks became more complex [F(2,7)=6.69; P<0.001]. This increase differed across the three groups [significant interaction effect; F(2,7)=3,31; P<0.001] because particularly patients produced motor errors during the more complex tasks. In both control groups, 62% performed all eight consecutive tasks without errors in the motor components. In contrast, only 8% of the patients completed all tasks without motor errors (log rank test, P<0.0001). This difference between patients and controls disappeared if the cognitive component was also scored, because more controls made cognitive errors during complex tasks than patients. Controls apparently gave priority to execution of the motor components, which they performed significantly faster than the patients. Both patients and controls made more errors during the shortened MTT, suggesting that learning effects (gain in performance through practice) influenced performance on the complete test. The MTT is a new balance test that clearly discriminates between healthy subjects and PD patients. Unlike controls, PD patients lend less priority to motor tasks over cognitive tasks. In addition, impaired motor learning may partially explain the higher error rate in PD. Future studies must determine if impaired MTT performance can predict actual falls in daily life. [ABSTRACT FROM AUTHOR]

Vestibular function was studied in a group of 121 patients with unilateral vestibular schwannomas who were referred to University Hospital Utrecht between 1986 and 1996. Testing included the caloric test, torsion test, saccade test, smooth pursuit test and the registration of spontaneous nystagmus. Each patient’s symptoms were taken from a chart review. The size of the tumor was expressed as the maximum extrameatal diameter in the axial plane parallel to the petrous ridge as seen in magnetic resonance imaging or computed tomography. Large tumors were significantly more often accompanied by a more severe paresis on caloric testing, a smaller gain on torsion testing, spontaneous nystagmus, an abnormal saccade test and an abnormal smooth pursuit test. The presence of spontaneous nystagmus was significantly more frequently combined with an abnormal smooth pursuit and saccade test. There was a significant correlation between the slow component’s velocity of the spontaneous nystagmus and the size and progression of tumor. However, a specific relation between tumor size and central vestibular compensation could not be demonstrated. [ABSTRACT FROM AUTHOR]

Abnormal automatic postural responses are thought to contribute to balance impairment in Parkinson’s disease. However, because postural responses are modifiable by stance, we have speculated that some postural abnormalities in patients with Parkinson’s disease are secondary to their stooped stance. We have studied this assumption by assessing automatic postural responses in 30 healthy subjects who were instructed either to stand upright or to assume a typical parkinsonian posture. During both conditions, subjects received 20 serial 4°’toe-up’ rotational perturbations from a supporting forceplate. We recorded short-latency (SL) and medium-latency (ML) responses from stretched gastrocnemius muscles and long-latency (LL) responses from shortened tibialis anterior muscles. We also assessed changes in the center of foot pressure (CFP) and the center of gravity (COG). The results were qualitatively compared to a previously described group of patients with Parkinson’s disease who, under these circumstances, typically have large ML responses, small LL responses and insufficient voluntary postural corrections, accompanied by a slow rate of backward CFP displacement and an increased posterior COG displacement. The stooped posture resulted in unloading of medial gastrocnemius muscles and loading of tibialis anterior muscles. Onset latencies of stretch responses in gastrocnemius muscles were delayed in stooped subjects, but the onset of LL responses was markedly reduced. Amplitudes of both ML and LL responses were reduced in stooped subjects. Prestimulus COG and, to a lesser extent, CFP were shifted forwards in stooped subjects. Posterior COG displacement and the rate of backward CFP displacement were diminished in stooped subjects. Voluntary postural corrections were unchanged while standing stooped. These results indicate that some postural abnormalities of patients with Parkinson’s disease (most notably the reduced LL responses) can be reproduced in healthy subjects mimicking a stooped parkinsonian posture. Other postural abnormalities (most notably the increased ML responses and insufficient voluntary responses) did not appear in stooped controls and may contribute to balance impairment in Parkinson’s disease. [ABSTRACT FROM AUTHOR]

The article relates the authors' comments on the study on vasovagal syncope (VVS) by P. Alboni, M. Alboni and G. Bertorelle. The authors commend the study's contributions to the theory of fainting and the review of the literature on why animals do not faint and on a potential paleolithic origin of syncope in the human genetic lineage. However, the authors argue on the study's theory that VVS is beneficial to human beings since its expression suggests a response that has gone out of control.

A letter to the editor about high frequency repetitive transcranial magnetic stimulation over the motor cortex as diagnostic value for narcolepsy is presented.

We report a 20-year- old sportsman with frequent attacks of lightheadedness, chest pain, blurred vision and falls during and shortly after exercise. Cardiac and pulmonal evaluation and routine autonomic function tests were normal apart from a relatively high resting heart rate (70 bpm) compared to endurance-trained men. In view of the relation to exercise, the patient was asked to cycle with maximal effort on an ergometer with continuous blood pressure (BP), heart rate (HR) and electroencephalogram (EEG) registration. Immediately after cessation of exercise a brief hypotensive period (75/45 mmHg) occurred together with sinus tachycardia (180 bpm) during which the patient experienced his typical complaints. We hypothesized that our patient's symptoms were primary related to sympathetic failure. As water drinking has been demonstrated to raise sympathetic activity rapidly, we undertook a second cycling test after ingestion of 1000 mL tap water. Symptoms nor hypotension recurred. Because of the short lasting press or effect and its minimal side effects, we suggest water drinking as simple and possible effective therapy for idiopathic exercise-related syncope. [ABSTRACT FROM AUTHOR]