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Infiltrative non-GBM gliomas are common primary intracranial malignancies, and postoperative adjuvant radiotherapy is recommended for most adult patients diagnosed with this disease to enhance local control and prolong intracranial progression-free survival (PFS). However, RT-related neurocognitive function (NCF) consequences should not be ignored. Early neurocognitive decline principally includes episodic memory, associated significantly with functions of the hippocampus. This prospective study aims to investigate the impact of adjuvant brain irradiation on neurocognitive performances and relevant oncological outcomes.Twenty-five patients with intracranial infiltrative non-GBM gliomas were enrolled when postoperative adjuvant RT was recommended. All recruited patients should receive baseline brain magnetic resonance imaging, and neuropsychological assessments before and 4 months after the RT course. A battery of neuropsychological measures, mainly including executive functions, memory, psychomotor speed and visuoconstructive ability, was used to evaluate NCFs of interest.Analyzing the delta values between post-irradiation and baseline NCF scores, we observed a robust trend reflecting cognitive stabilization rather than deterioration in almost all NCF. Both verbal and visual memory functions exhibited significant differences in the corresponding scaled scores (

Researchers have examined differences on ImPACT® in baseline symptom reporting and neurocognitive performances based on the language of administration and racial/ethnic identity. This is the first study to examine differences between student-athletes tested in Mandarin versus English on ImPACT® during preseason baseline assessments conducted in high schools in the United States. Participants included 252 adolescent student-athletes who completed ImPACT® testing in the state of Maine in Mandarin and 252 participants who completed testing in English, matched on age, gender, and health and academic history. Participants were compared on neurocognitive composite scores and symptom ratings. Boys tested in Mandarin, but not girls, had modestly better neurocognitive performance on one of four composite scores (i.e., Visual Motor Speed, p < .001, d = .45). Although language groups did not differ in total symptom severity, boys tested in Mandarin endorsed multiple physical symptoms at higher rates than boys tested in English. These results suggest that the current ImPACT® neurocognitive normative data are reasonably appropriate for use with adolescents evaluated in Mandarin. There were some differences in the reporting of physical symptoms, with greater rates of symptom endorsement by boys tested in Mandarin than boys tested in English; but overall symptom severity ratings were comparable between the language groups.

Conventional treatment for treating primary central nervous system lymphoma (PCNSL) has consisted of either whole-brain radiotherapy (WBRT) or methotrexate (MTX)-based combined modality therapy. However, delayed cognitive sequelae have emerged as a significant debilitating complication in PCNSL patients. A prospective observational case-series study with prospective assessments of neurocognitive functions (NCFs), neuroimaging, and activities of daily living in newly-diagnosed PCNSL patients was undertaken. A battery of neuropsychological measures, used to evaluate NCFs, is composed of ten standardized NCF tests, representing four domains sensitive to disease and treatment effects (executive function, attention, verbal memory, psychomotor speed), and activities of daily living. A total of 15 patients with newly-diagnosed PCNSL were consecutively enrolled in this study. Comparing the NCF scores between the baseline (before WBRT) and post-treatment (after combined chemoradiation therapy) intervals (Mean = 122.33 days, SD = 34.49, range = 77-196), neurobehavioral outcomes consistently remained improving or stable in almost each domain of NCF. Specifically, the scores on Paced Auditory Serial Addition Test-Revised (PASAT-R) were significantly improved between the baseline and post-chemoradiation assessment. Under the multidisciplinary treatment guidelines for treating patients with newly-diagnosed PCNSL, multi-domain NCF become stabilized and even improved after the course of conformal WBRT combined with or without MTX-based chemotherapy.

Headache, both before and after injury, has been associated with worse outcome following mild traumatic brain injury (MTBI). This study examined whether three MTBI patient groups - no headache (reported no pre-/post-injury headache), pre-injury headache (reported pre-injury headache, nearly all of whom also reported post-injury headache), and post-traumatic headache only (denied pre-injury headache and reported post-injury headache) - differed in acute-to-subacute outcomes.Cross-sectional observational study.Patients within 21 days of a MTBI (Neuropsychological test performances did not differ between headache groups. Participants with pre-injury headache and participants with post-traumatic headache only reported greater change in self-reported physical and cognitive symptoms than participants with no headache. Participants with pre-injury headache reported worse post-injury anxiety symptoms than participants with post-traumatic headache only.The pre-injury headache and post-traumatic headache only groups did not meaningfully differ in outcome within 21 days of MTBI, but they had worse physical and cognitive symptoms than participants with no headache. Future research should assess whether differences in outcome emerge further from injury and whether specific headache subtypes are differentially associated with outcome.

The relationships between postoperative functional improvement in various cognitive domains and regional hemodynamic change have not been sufficiently studied in childhood moyamoya disease (MMD). The present study aimed to examine the cognitive benefit of indirect revascularization, the underlying biological mechanism, and factors affecting surgical outcome in childhood MMD. Twenty-three patients with MMD aged under 20 years received neuropsychological examinations before and after indirect revascularization surgery, evaluating intellectual function, verbal and visual memory, and executive function. Among them, 13 patients had magnetic resonance perfusion (MRP) studies, in which regional cerebral perfusion was rated. Postoperative improvement was observed in verbal memory performances (p = 0.02–0.03) and in cerebral perfusion at all 26 cerebral hemispheres (p = 0.003–0.005), especially in the middle cerebral artery (MCA) territories (p = 0.001–0.003). Hemodynamic improvement in the left MCA territories was significantly correlated with improvement of both verbal new learning (p = 0.01) and intellectual function (p = 0.004). Postoperative cognitive improvement of immediate recall and verbal intellectual function was associated with female sex (r = − 0.42) and symptom duration (p = − 0.03), respectively. Hemodynamic improvement in the MCA territories was related to longer follow-up intervals (p = 0.02). The findings revealed that the selective postoperative cognitive improvement was associated with increased regional perfusion in the MCA territories, and indicate the importance of early intervention and the potential of indirect revascularization regarding long-term outcome.

PURPOSE/OBJECTIVE(S) Apolipoprotein E (APOE) polymorphism is a well-known risk associated with Alzheimer's disease. Its role in neurocognition decline after whole brain radiotherapy (WBRT) for brain metastases is not well-investigated. The present secondary analysis of a prospective blinded randomized controlled phase II trial aimed to evaluate the impact of APOE genotypes upon neurocognitive outcomes after WBRT with or without hippocampal avoidance. MATERIALS/METHODS Adult patients with brain metastases were stratified by prior radiosurgery and randomized to hippocampal avoidant conformal WBRT versus conformal WBRT without hippocampal avoidance to 30 Gy in 10 fractions from March 2015 to November 2018. Memantine was not used during or after WBRT. Standardized neurocognitive test battery (Hopkins Verbal Learning Test-Revised [HVLT-R], Trail Making Test), was performed at baseline, 1, 2, 4, 6, and every 3 months up to two years by trained independent health professionals. Both clinical trial participants and examiners were blinded to the treatment group assignment. APOE alleles were determined by the genome-wide genotyping. The association between APOE genotypes and neurocognitive outcomes was analyzed by general linear model. The role of APOE genotypes on the effect of hippocampal avoidance during WBRT was also evaluated. Factorial ANOVA was used to assess the independent factors associated with neurocognitive outcomes. RESULTS Among 65 analyzable patients, APOE genotyping was available for 64.6% (n = 42) of patients. The most frequent APOE allele was e3 homozygote (e3/e3, n = 24), followed by e2 carrier (e2/e3, n = 11) and e4 carrier (e4/e3, n = 7). No differences in baseline characteristics and cognitions between patients of different APOE genotypes. At 6-month, patients carrying APOE e2 and e4 allele had the best and worst preservation in HVLT-R total recall (mean difference, e2: +3.18 versus e4: -3.20, P = 0.008), and delayed recall (mean difference, e2 carrier: +0.46 versus e4 carrier: -2.40, P = 0.03), respectively. The effect of preservation in 6-month memory score is the strongest in the APOE e2 carriers followed by the APOE e3 homozygotes, and the least in the APEO e4 carriers in order (P = 0.028). Only patients of APOE e3 homozygotes showed improved preservation in late memory score by hippocampal avoidant WBRT at 6-month (mean difference, hippocampal avoidant: +3.67 versus conformal: -3.18, P = 0.037) and beyond. APOE genotyping was independent of age and hippocampal avoidance to be associated with the preservation of 6-month HVLT-R total recall (P = 0.042), and HVLT-R delayed recall (P = 0.032). CONCLUSION The APOE genotype is associated with the risk of memory decline after WBRT. Specifically, APOE e2 carriers exhibited better while e4 carriers showed worse perpetuation in verbal memory function after WBRT. APOE e3 homozygotes but not APOE e2 or e4 carriers benefit late memory preservation by hippocampal avoidant WBRT for brain metastases.

Background:The coronavirus disease 2019 (COVID-19) outbreak is a global public health crisis that has affected the implementation of advance care planning (ACP) in Taiwan. The purpose of this study is to (1) confirm that COVID-19 significantly reduced public participation in ACP, (2) identify factors influencing the implementation of ACP during the COVID-19 pandemic and how they differ from those before the COVID-19 outbreak.Methods: An observational study from retrospective review of medical chart and clinical information.This is a hospital-based study to examine the characteristics of ACP implementation in Taiwan during COVID-19. A total of 1,253 participants were recruited, including 916 people who had completed ACP from September through December 2019, and 337 people from January through April 2020.Results:This study representing an approximately 65% decrease in ACP participation after COVID-19 outbreak. The cancellation rate of ACP during COVID-19 is higher before outbreak. After COVID-19 outbreak, Participation rate of disadvantaged populations increased from 16.92% to 21.66%. The percentage of participants with caregiver experiences decreased from 31.66%to to 23.44% . Participants who did not wish for their families to bear decision-making responsibilities increased from 44.00% to 52.52%. The percentage of offspring participation increased from 86.57% to 90.80%. The percentage of individuals completing ACP after the outbreak without signing an advance directive increased from 5.57% to 9.20%. The COVID-19 pandemic significantly reduced participation in ACP. Conclusions: This study directly compared the ACP implementation before and after COVID-19, which is a tremendous global health crisis influencing the conceptions of life and death.COVID-19 has threatened the public’s health and has changed ACP in the healthcare system by increasing public awareness of the topic of death. After COVID-19, both medical staff and the public should clearly express their opinions on terminal care.Policy supports and active participation of medical team can encourage disadvantages to complete ACP.Healthcare workers should provide palliative and terminal care services in which patient comfort and dignity are the primary focus of care.Trial registration:This study was approved on 3 June 2020 by the Taipei City Hospital Institutional Review Board (Case No.: TCHIRB-10808008-E).

Researchers have examined differences on ImPACT

A complicated mild traumatic brain injury (MTBI) is defined as mild by all clinical severity indicators but is complicated due to a traumatic intracranial abnormality visible on neuroimaging. Researchers have reported mixed findings regarding whether neuropsychological and functional outcomes following complicated MTBI are worse than, or similar to, outcomes following uncomplicated MTBI. This study examined patients referred from a Taiwanese emergency department to a neurosurgical outpatient clinic. Participants with complicated MTBI, uncomplicated MTBI, and those who did not undergo head computed tomography (CT) were compared on psychological, neuropsychological, and post-concussion symptom outcomes within 21 days of injury.Participants with complicated MTBI (No significant differences were observed between groups on any measure. For individual post-concussion symptoms, dizziness, anxiety, and attention difficulty were endorsed more often after uncomplicated MTBIs, but these group differences were not significant after controlling for multiple comparisons.Participants with complicated MTBIs did not have worse acute or subacute outcomes than participants with uncomplicated MTBIs or no head CT. These results are consistent with many studies finding comparable outcomes between those with complicated and uncomplicated MTBIs. This study is limited by small sample size and minimal information on intracranial abnormalities, broadly categorizing groups based on positive or negative neuroimaging as opposed to specific lesion types and locations.

BackgroundHippocampal avoidance whole-brain radiotherapy (HA-WBRT) shows potential for neurocognitive preservation. This study aimed to evaluate whether HA-WBRT or conformal WBRT is better for preserving neurocognitive function.MethodsThis single-blinded randomized phase II trial enrolled patients with brain metastases and randomly assigned to receive HA-WBRT or conformal WBRT. Primary end point is the decline of Hopkins Verbal Learning Test–Revised (HVLT-R) Delayed Recall at 4 months after treatment. Neurocognitive function tests were analyzed with a mixed effect model. Brain progression free survival (BPFS) and overall survival (OS) were estimated using the Kaplan–Meier method.ResultsPatients were enrolled from March 2015 to December 2018 with a median follow-up of 12.4 months. A total of 70 patients were randomized. No differences in baseline neurocognitive function existed between the two arms. There were no differences in any neurocognitive assessments at four months. At six months, patients receiving HA-WBRT showed favorable perpetuation of HVLT-R total recall (mean difference = 2.60, p = 0.079) and significantly better preservation of the HVLT-R recognition-discrimination index (mean difference = 1.78, p = 0.019) and memory score (mean difference = 4.38, p = 0.020) compared with patients undergoing conformal WBRT. There were no differences in TMT part A, part B, or the COWA test between the two arms at any time point. There were no differences in BPFS or OS between arms as well.ConclusionsPatients receiving HA-WBRT without Memantine showed better preservation in late verbal memory, but not in verbal fluency or executive function.

A flow-sediment rating curve is used to describe the relation between flow discharge and suspended-sediment concentration for a specific location. Five types of flow-sediment rating curves - single-valued line, clockwise loop, counterclockwise loop, single-valued line plus loop, and figure eight - were found to rely on the flow and available sediment arriving at the measuring site. In this study, equations for flow and sediment travel time were derived according to soil, rainfall, and watershed geomorphologic characteristics. The hysteresis of the rating curve was related to the travel times by a series of numerical tests. Field data collected from the Goodwin Creek Experimental Watershed, Mississippi, United States were used to verify the proposed rating curve hysteresis analysis. The results indicate that when the flow travel time is more extended than the sediment travel time, the rating curve shows a clockwise loop. A counterclockwise loop in the rating curve shows that the flow travel time is less extended than the sediment travel time. If the flow travel time exceeds the sediment travel time in specific runoff states and is less than the sediment travel time in other runoff states, then a single line plus a loop rating curve or a figure-eight rating curve is observed. The criterion for the model parameters to obtain equalization of the flow and sediment travel times was derived, which can identify the type of flow-sediment rating curve in a specific watershed.

A nonstoichiometric Si1− x Ge x with composition ratio dependent saturable absorption prepared by vaporized synthesis and chemical exfoliation is performed to passively mode-lock the Erbium-doped fiber laser (EDFL). The Si1− x Ge x with varied Ge/Si composition ratio from 3 to 16 exhibits tunable nonlinear modulation depth from 17% to 22%, where the Si1− x Ge x with the highest Ge content performs the largest nonlinear modulation depth. When operating the EDFL in the self-amplitude modulation region, the Si1− x Ge x with Ge/Si composition ratios of 3, 9, and 16 self-starts the EDFL pulsation with pulsewidths of 820, 760, and 730 fs. When operating the EDFL in high gain region, the self-phase modulation induced soliton compression dominates the repulsation of passively mode-locked EDFL, which slightly shrinks the EDFL pulsewidth from 346 to 338 fs. All these demonstrations are premier and important to explore the superior nonstoichiometric Si 1− x Ge x saturable absorbers for ultrafast fiber lasers.

Although 'return to work' (RTW) has been always emphasized for patients with mild traumatic brain injury (MTBI), methodological drawbacks weakened its representativeness. This study thus aims to evaluate the 'work quality' (WQ) which originated from 'working status' and 'working stability' simultaneously, and to further explore the associations among post-concussion symptoms (PCS), neuropsychological functions and WQ.A total of 179 participants, which included 132 patients with MTBI and 47 healthy participants, were prospectively recruited. The work quality index (WQI) was developed to evaluate WQ. All patients were evaluated for their PCS, neuropsychological functions and WQ at two weeks post-injury (T1), while PCS and WQ were recorded by one month post-injury (T2).More than half of the patients were not able to retain their pre-injury jobs at T1, while 26% of the patients still failed to regain previous works at T2. Interestingly, WQ was significantly associated with educational levels and physical PCS, such as headache and dizziness.Simultaneously considering working status and stability to reveal the quality of RTW is merited. A higher educational level might be a protective factor for successful RTW, and ameliorating physical symptoms is also necessary to get favourable WQ by one month after MTBI.

The objective of this study was to compare patients with acute-to-subacute mild traumatic brain injury (mTBI) on post-concussion symptom reporting based on whether they retrospectively recalled experiencing pre-injury anxiety or depression. Patients with mTBI (

Objective Postconcussion symptoms (PCS) are commonly reported by patients with mild traumatic brain injury (MTBI). Although PCS significantly recovered by 3-month postinjury, a number of patients still experienced persistent PCS for >1 year. As few researchers investigated long-term PCS endorsement, the present study thus aims to show the latent structure of long-term PCS and further uncover its associating factors. Methods In total, 110 patients with MTBI and 32 healthy participants were prospectively enrolled. PCS was evaluated at 2 weeks and long-term evaluations (mean = 2.90 years) after MTBI. In addition, cognitive functions, which include memory, executive function, and information processing, and emotional disturbances, which include depression, anxiety, and irritability, were also examined at 2-week postinjury. Results Patients reported significantly more PCS at 2-week postinjury than healthy participants did, but PCS significantly improved at long-term evaluations when comparing with PCS at acute stage after MTBI. Both of PCS at 2 weeks and long-term evaluations can be further subdivided into subgroups based on the severity of PCS, in which specific PCS (e.g., fatigue, loss of energy, insomnia, slowness of information processing, irritability, and blurred vision) can be well differentiated among subgroups at long-term evaluations. Conclusions This study directly showed the characteristics of long-term PCS and associating factors. It further evidenced that specific physical, cognitive, and emotional symptoms might be determinant to identify the subgroups of patients with long-term PCS endorsement.

Objective Quality of life (QoL) has been identified as one of the most important outcome measurements following cervical spine surgery. The contributing factors to post-operative QoL remain limited. This study thus aimed to prospectively examine the QoL and related pre-operative emotional factors in patients who underwent anterior cervical spine surgery. Patients and methods A total of 124 patients who underwent anterior cervical spine surgery were recruited. All participants were prospectively evaluated for their QoL and 2 aspects of emotion, depression and anxiety, before and after surgery, respectively. Results Pre-operatively, 13% of patients showed signs of depression and 31% of patients reported symptoms of anxiety. Post-operatively 14% of patients reported depression, but 41% reported symptoms of anxiety. A significant association between depression, anxiety and different domains of QoL were identified, and specific cut-off points of pre-operatively depressive and/or anxiety levels to predict unfavorable post-operative QoL were further established. Conclusions This prospective study demonstrated specific emotional factors, specifically depression and anxiety, influence patients’ QoL following surgery. These results suggest clinicians should also monitor patients’ emotional adjustments with their physical conditions.

Objective Patients who experience a mild traumatic brain injury (MTBI) may have a headache condition preceding injury, develop a post-traumatic headache after injury, or experience headache neither before nor after injury. This study examined whether MTBI patients with no headache, pre-existing headache, and post-traumatic headache differed in acute-to-subacute outcomes. Method Patients with MTBI were recruited from an outpatient neurosurgery clinic in Taipei, Taiwan after emergency department referral (N = 291; 40.2% men; M = 37.9 ± 13.9 years-old; Mdn = 7 days-since-injury, range = 0–21), completing neuropsychological tests of attention, memory, and verbal fluency and questionnaires evaluating depression, anxiety, and post-concussion symptoms. Participants with no headache (reported neither pre- or post-injury), pre-existing headache (reported pre-injury headache, of whom some reported worsened post-injury headache), and post-traumatic headache (denied pre-injury headache, reported post-injury headache) were compared using non-parametric ANCOVA, controlling for gender and days-since-injury. Results Neuropsychological test performances did not differ between headache groups. Participants with pre-injury headache and post-traumatic headache had greater change in self-reported physical (F = 25.52, p Conclusion(s) Participants with pre-injury and post-traumatic headache did not differ in outcome within 21 days of injury but had worse self-reported physical and cognitive symptoms than participants with no headache. Most participants with pre-injury headache experienced worsened headache following MTBI (53.7%). Future research is needed to assess whether more specific headache subtypes are differentially associated with MTBI outcome.

Ultrathin amorphous Ge (α-Ge) film is synthesized as nonlinear saturable absorber to enable the femtosecond pulsation of erbium-doped fiber laser, which self-starts the fiber laser pulsation with nearly 700-fs pulsewidth at threshold pumping condition. Under high-gain condition, the α-Ge film with thickness of 17 nm exhibits the largest self-amplitude modulation coefficient of 8.9 × 10−4 to further compress the fiber laser pulsewidth to 305 fs. To compare, other Si-doped Ge films are also synthesized by linearly decreasing the Ge/(Ge + Si) composition ratio during plasma enhanced chemical vapor deposition, which reveal ultrahigh Ge/Si composition ratios with bandgap energy tunable from 1.05 to 0.87 eV. All recipes perform relatively comparable mode-locking force for pulsating the fiber laser with corresponding self-amplitude modulation coefficient degraded only by 6 × 10−6 as compared to the pure α-Ge film. Decreasing the Ge/(Ge + Si) composition ratio by 5% only broadens the fiber laser pulsewidth by 8.2% to 330 fs and slightly increases the peak amplitude fluctuation of the pulse-train to 1.81%. These results corroborate the pulsating stability of fiber laser under high pumping condition via the ultrathin α-Ge even with residual Si dopants, indicating that the pure α-Ge can serve as the optimized group-IV semiconductor nonlinear saturable absorption to provide sufficiently large nonlinear saturable absorbance as well as self-amplitude modulation, particularly suitable for stabilization the pulsed fiber laser no matter in the initial mode-locking or in the soliton compression regime.

Objective Student athletes commonly complete baseline preseason assessments of neurocognitive performances and symptom reporting using ImPACT®. Some past researchers have examined differences in performances and symptoms based on language of administration and racial/ethnic identity. This study examines differences between Mandarin-speaking and English-speaking student athletes on ImPACT® at preseason assessments. Method Participants included 252 adolescent student athletes who completed preseason baseline ImPACT® testing in Mandarin and 252 participants who completed testing in English, matched on age, gender, and health and academic history. These groups were compared on neurocognitive composite scores and symptom ratings. Results Mandarin-speaking athletes performed modestly better on one of five neurocognitive composite scores (Visual Motor Speed, p Conclusions These results suggest that the current ImPACT® neurocognitive normative data are reasonably appropriate for use with Mandarin-speaking adolescents. When back translated, a few Mandarin-language symptoms were not semantically equivalent to their corresponding English-language symptoms, but no group differences were observed for these symptoms. Modest language group differences were observed in physical symptom reporting, more so in boys than girls. Individuals of Asian descent are more likely to express their mental health concerns in somatic terms, and greater physical symptoms in Mandarin-speaking boys could correspond to an expression of psychological distress. Clinicians should be mindful of psychological functioning at baseline testing and post-concussion evaluations because students who do not identify with the dominant culture of their sporting environment might experience acculturative stress.

In managing patients with brain metastasis in the disciplines of neuro-oncology, neurosurgery, and radiation oncology, intracranial control and care. Of note, the controversies and problems associated with delayed radiation-related cognitive dysfunction cannot be ignored, particularly in patients who have undergone whole-brain radiation therapy (WBRT). Concerning neurocognitive consequences related to cranial irradiation, previous studies have shown that impaired hippocampal neurogenesis may be responsible for such cognitive impacts resulting from the delivery of WBRT. Therefore, it has been hypothesized that conformal hippocampal sparing during the course of WBRT (HS-WBRT) would contribute to meaningful preservation with regard to neurocognitive functions (NCFs).

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an uncommon disease. Conventional treatment has consisted of either whole-brain radiotherapy (WBRT) or methotrexate (MTX)-based combined modality therapy combining chemotherapy and cranial irradiation. The addition of chemotherapy to cranial RT has significantly improved survival outcomes. However, delayed treatment-related cognitive sequelae have emerged as a significant debilitating complication of combined modality treatment in PCNSL patients, especially when effective treatment can result in disease control and greater survival. Furthermore, the specific contribution of the disease per se and various treatment modalities to cognitive impairment remains unclear because it is difficult to differentiate the individual neurotoxic effects of combined modalities when each can lead to cognitive dysfunctions respectively. METHODS: A prospective observational cohort study with longitudinal assessments of neurobehavioral functions, neuroimaging, and activities of daily living in newly-diagnosed PCNSL patients was undertaken at our institute. Neurobehavioral outcomes were integrated into this prospective study and a battery of neuropsychological measures was used to evaluate neurocognitive functions (NCFs). The battery is composed of ten standardized NCF tests, representing four domains sensitive to disease and treatment effects (executive function, attention, verbal memory, psychomotor speed), and activities of daily living. RESULTS: Totally 15 patients with newly-diagnosed PCNSL including two cases with primary intraocular lymphoma were consecutively enrolled from February 2014 to January 2018. Comparing the differences in NCF scores between the baseline and post-treatment intervals, neurobehavioral outcomes consistently remained improving or in almost every domain evaluated in this study. Specifically, the scores of executive functions based on Paced Auditory Serial Addition Test (PACT) significantly improved between the baseline and post-chemoradiation assessment (Wilcoxon rank sum test, p = 0.016). CONCLUSIONS: Under the multidisciplinary treatment guidelines implemented at our institute, both improving neurobehavioral outcomes and maintaining oncological outcomes can be achieved.

Background: Prominent executive dysfunction can differentiate vascular dementia from Alzheimer disease (AD). However, it is unclear whether the Frontal Assessment Battery (FAB) screening tool can differentiate subcortical ischemic vascular disease (SIVD) from AD at the pre-dementia stage. In addition, the neural correlates of FAB performance have yet to be clarified. Methods: Patients with mild cognitive impairment (MCI) due to SIVD (MCI-V), MCI due to AD (MCI-A), and demographically matched controls completed the Mini-Mental State Examination, Taiwanese FAB (TFAB), Category Fluency, and Chinese Version of the Verbal Learning Test, and underwent magnetic resonance imaging. White matter hyperintensities were rated according to the Scheltens scale. Results: TFAB total scale and its Orthographical Fluency subtest were the only measures that could differentiate MCI-V from MCI-A. Discriminative analysis showed that Orthographical Fluency scores successfully identified 73.2% of the cases with MCI-V, with 85.0% sensitivity. Orthographical Fluency scores were specifically associated with lesion load within frontal periventricular, frontal deep white matter, and basal ganglia regions. Conclusion: The TFAB, and especially its 1-min Orthographical Fluency subtest, is a useful screening procedure to differentiate MCI due to SIVD from MCI due to AD. The discriminative ability is probably due to frontosubcortical white matter pathologies disproportionately involved in the two disease entities.

The Frontal Assessment Battery (FAB) is commonly used to evaluate executive functions. Although psychometric properties have been examined in Western studies, data on the FAB in Eastern societies are limited. This study thus aims to examine psychometric properties of the Taiwanese FAB (TFAB). A total of 301 healthy participants were recruited. All participants were evaluated with the TFAB. Thirty participants were retested 3 months after the 1st examination for test-retest reliability. The Verbal Fluency Test was used for criterion-related validity. Although the TFAB had an unacceptable Cronbach's alpha, its test-retest reliability was good. The criterion validity was also good, while the factor analysis revealed that the TFAB may be represented as a 2-factor or 3-factor structure. The TFAB score was significantly associated with age and education level. This study comprehensively re-examined the psychometric properties of the TFAB for Chinese-speaking people, and it merited more validations for the TFAB with clinical samples in the future.

To evaluate irritability in patients with mild traumatic brain injury (mTBI) and moderate-to-severe traumatic brain injury (msTBI), respectively.A prospective study was conducted at a level I trauma centre.A total of 160 participants, which included 80 healthy subjects and 80 patients with TBI, were recruited. Irritability was assessed by the National Taiwan University Irritability Scale and other cognitive functions, which included memory, executive function and information processing, were also evaluated.The results showed post-injury self-reported irritability in patients with mTBI and family-reported irritability in patients with msTBI were significantly higher than irritability reported by healthy participants. Irritability was significantly associated with information processing ability in patients with mTBI, but it was not associated with any cognitive functions in patients with msTBI.Irritability was found to be prominent after TBI. Divergent causes of irritability seemed apparent in patients with mTBI and msTBI. Irritability after mTBI appeared might be related to the cognitive functions disrupted after the injury, whereas irritability after msTBI appeared to result directly from the brain lesions involved.

Objective Patients with mild traumatic brain injury (MTBI) usually suffer from the post-concussion symptoms (PCS). PCS could recover by 3 months post-injury, but some patients still persistently complain of those symptoms for years. Accordingly, the Chang-Gung University Brief Intervention for Post-Concussion Symptoms (CGU-BIPCS) was developed to intervene PCS based on the established advantages of health education. This prospective study thus aims to evaluate the effectiveness of CGU-BIPCS for patients with MTBI. Methods A total of 130 participants, which included 53 healthy participants and 77 patients with MTBI. Patients were further subdivided as two groups: "regular intervention" (RI) and "health education intervention" (EI). PCS of patients with MTBI were respectively evaluated at 2 weeks and 3 months post-injury, and symptoms of healthy participants were also examined. Results Both patients in RI and EI reported significantly more PCS than healthy participants did at 2 weeks and 3 months post-injury but less PCS at 3 months than at 2 weeks post-injury. However, the PCS endorsement of patients in RI and EI were not significantly different. In addition, more patients in EI reported significantly PCS deterioration than patients in RI did at 3 months post-injury. Conclusions Although establishing the effectiveness of CGU-BIPCS was unsuccessful in this study, it is further suggested that a potential iatrogenic effect from this kind of early interventions should never be overlooked.

Hepatitis C virus (HCV) is a global health problem, affecting approximately 3% of the world's population. The standard treatment for HCV infection is often poorly tolerated and ineffective. Therefore, the development of novel or more effective treatment strategies to treat chronic HCV infection is urgently needed. In this report, BP008, a potent small-molecule inhibitor of HCV replication, was developed from a class of compounds with thiazol core structures by means of utilizing a cell-based HCV replicon system. The compound reduced the reporter expression of the HCV1b replicon with a 50% effective concentration (EC 50 ) and selective index value of 4.1 ± 0.7 nM and >12,195, respectively. Sequencing analyses of several individual clones derived from BP008-resistant RNAs purified from cells harboring HCV1b replicon revealed that amino acid substitutions mainly within the N-terminal region (domain I) of NS5A were associated with decreased inhibitor susceptibility. Q24L, P58S, and Y93H are the key substitutions for resistance selection; F149L and V153M play the compensatory role in the replication and drug resistance processes. Moreover, BP008 displayed synergistic effects with alpha interferon (IFN-α), NS3 protease inhibitor, and NS5B polymerase inhibitor, as well as good oral bioavailability in SD rats and favorable exposure in rat liver. In summary, our results pointed to an effective small-molecule inhibitor, BP008, that potentially targets HCV NS5A. BP008 can be considered a part of a more effective therapeutic strategy for HCV in the future.

This study aimed to identify early radiologic signs that are predictive of hemorrhage progression and clinical deterioration in patients with traumatic cerebral contusion. We hypothesized that contrast extravasation (CE) and blood-brain barrier disruption might be associated with hemorrhage progression, brain edema, and clinical deterioration in these patients.Twenty-two patients with traumatic cerebral contusion (diagnosed on initial noncontrast head computed tomography [CT]) who initially did not require surgical intervention were enrolled in this study. Contrast-enhanced and perfusion CT scans were performed within 6 hours of injury, and follow-up noncontrast CT scans were performed at 24 hours and 72 hours.In each noncontrast CT scan, the volumes of the contusion hemorrhage and edema were calculated using computerized planimetric techniques. The initial Glasgow Coma Scale, hemorrhage progression, clinical deterioration, and the need for subsequent surgery were recorded. The early radiologic findings were compared with these parameters and functional outcome at 6 months to identify predictive radiologic signs. CE was present in 9 of 22 patients (41%) and was highly associated with hemorrhage progression (p0.05), clinical deterioration (p0.01), and need for subsequent surgery (p0.01). In addition, patients with CE had a greater volume of edema at 24 hours (p0.01) and 72 hours (p0.01) than those who did not have CE. However, CE was not found to be associated with poor outcome.Early parenchymal CE is associated with hemorrhage progression, cerebral edema, clinical deterioration, and need for subsequent surgery. These patients should be monitored closely, and early surgery may be needed if deterioration occurs. Further elucidation of the pathophysiology is needed to formulate effective treatment for these high-risk patients.

Irritability is not uncommon after traumatic brain injury (TBI). Unfortunately, no instruments are available to directly measure this clinical feature. This study thus aimed to develop a specific scale to evaluate the irritability for patients with TBI. A total of 144 participants, which include 80 healthy participants and 64 patients suffering from TBI, were recruited. Irritability was assessed by the National Taiwan University Irritability Scale (NTUIS). Our results showed the NTUIS has good reliability. The factor analysis further revealed 2 different components: annoyance, and verbal aggression. Moreover, both self-reported and family-reported irritability postinjury were significantly higher than the irritability reported by the healthy participants. Indeed patients with TBI have significant problems with irritability after injuries, and thus a more specific assessment tool to carefully evaluate patients' irritability should be used.

Isolated oculomotor nerve palsy after mild head injury is rare. Only a few case reports have described the clinical presentation of these patients, and clinical and functional outcome have not been discussed in depth. The outcome of 10 patients with mild head injury in whom imaging studies ruled out other possible causes of oculomotor palsy was assessed during follow-up using the Glasgow Outcome Scale–Extended (GOSE). We suggest that limited eye movement is a major factor that negatively affects functional status after mild head injury.

To examine the long-term global clinical outcomes of TBI patients from 1 week to 10 years post-injury.A retrospective study was conducted at a level I trauma centre.A total of 327 TBI patients were recruited retrospectively in this longitudinal study and the score of Glasgow Outcome Scale Extended (GOSE) was then documented as an indicator of the clinical outcomes.The results presented that less than one-in-three patients recovered well within 2 weeks after trauma. Around 40% of patients were evaluated as favourable outcomes within 6 months post-injury. Less than 30% of TBI patients could gain favourable outcomes at 3 years post-injury and over half of patients still could not recover well at 6 years. Five patients' outcomes were continuously followed until 10 years and the results indicated that they started to have good outcomes after 3 years post-injury.This study might be the first one to longitudinally evaluate the outcomes of patients from 1 week to 10 years post-injury and revealed that patients still may have difficulties in social interactions and family relationships until 6 years post-injury, even though they could live and work independently. Hence, professionals should pay attention to the underlying factors causing their difficulties within the long-term recovery process.

Project delivery method of Build-Operate-Transfer (BOT) increases the commencement probability of public construction works through private investments. Public construction works worldwide that adopt the BOT model as their project delivery method are increasing gradually. Although many BOT projects have been implemented at various stages, some projects encounter major obstacles for advancement. This study attempts to identify the delay causes in various stages of BOT projects. Opinions of BOT participants’ replies are solicited using two questionnaire surveys. Those outcomes are analyzed using by traditional statistical methods and structural equation modeling method. Study results reveal that the stage of ‘negotiation and signing of concession agreement’ is the most essential stage, in which ‘improper contract planning,’ ‘debt problem’ and ‘uncertainty on political issues and government-finished items’ are the most significant delay causes. Identified causes of delay can be used to prevent the postponement of future BOT projects.

Concentrated rainfall usually results in serious soil erosion on steep hillslopes. Since the itinerary of the eroded sediment is complicated, estimating watershed erosion during storms is practically difficult. A physically-based approach for sediment yield estimation during storms was proposed in this study. By using soil and watershed geomorphologic information, analytical solutions for sediment travel time in different orders of overland areas and channels were derived to develop a geomorphologic instantaneous unit sedimentgraph (GIUS) which showed the temporal distribution of sediment discharge resulting from an instantaneous rainfall excess input. The resultant GIUS was a function of the rainfall excess intensity and sediment delivery ratio. The linearity restriction of the unit hydrograph theory was relaxed. Sediment yields during storm events were calculated by convoluting rainfall intensities with the proposed GIUS, which had been verified by using data from the Goodwin Creek Experimental Watershed in Mississippi, the United States. The simulated and the measured sediment yields were in good agreement for the test storms. Sensitivity of the sedimentgraph to the model parameters was also investigated. The proposed model was considered a promising application for sediment yield estimation in the field of water resources design.

We retrospectively reviewed the clinical experience of 30 patients with brain stem cavernous malformations (BSCM) treated operatively and non-operatively at our hospital between 1983 and 2005 to elucidate the natural history of BSCM and the factors that affect surgical outcome. Inpatient charts, imaging studies, operative records, and follow-up results were evaluated. The average follow up was 48.5 months. Twenty-two patients (73.3%) received surgical extirpation and of these 86.4% improved or stabilized and 13.6% deteriorated with permanent or severe morbidity. There was no mortality. Size, preoperative status, and surgical timing were factors related to surgical outcome. In the non-operative group, 50% of the patients were the same or better, 25% deteriorated, and 25% died. With appropriate patient selection, resection of BSCM can be achieved with acceptable morbidity compared with the ominous natural history of these lesions.

Primary objective: To identify the early clinical features of patients with mild traumatic brain injury (mTBI) that are predictive of the presence of persistent post-concussion symptoms (PPCS). Research design: A prospective study was conducted at a level I trauma centre. Methods and procedures: One hundred and eighty mTBI patients participated in this study. The post-concussion symptoms (PCS) were evaluated with a PCS checklist. All patients were examined at 1, 2 and 8 weeks post-injury. The chi-square test was used to evaluate the associations of each PCS and the logistic regression was used to identify potential predictors of mTBI patients who might suffer from PPCS. Main outcomes and results: Less than one-tenth of the mTBI patients examined complained of PPCS at 2 months after head trauma. Patients with PPCS are more likely to suffer from intracranial lesions. Moreover, clinical symptoms at 1 and 2 weeks post-injury, especially physical ones including headache, dizziness and fatigue, were reported significantly more often by patients with PPCS. Conclusions: This study showed that early clinical symptoms and intracranial lesions may be strongly associated with the presence of PPCS. Thus, those specific characteristics may be used as early indicators of long-term difficulties.

Objective: It has been noted that the posterior circulation serves as an important source of collateral blood supply in moyamoya disease. Since most of the literature has focused on non-operative cases and many symptomatic patients receive surgical revascularization, we evaluated the posterior circulation changes after revascularization and found that progressive posterior cerebral artery (PCA) steno-occlusive changes after revascularization caused cerebral hemodynamic compromise and clinical deterioration in a significant portion of patients. Methods: Twenty-three moyamoya disease patients with ischemic presentation who received revascularization with complete angiography and xenon CT during a minimum of 3 years’ clinical follow-up were enrolled. Revascularization was performed in 38 hemispheres. Pre- and postoperative angiography were reviewed to determine the internal carotid artery (ICA) stage, PCA stage, leptomeningeal collateral (LMC) grade, and Matsushima synangiosis grade. The postoperative regional cerebral blood flow (CBF) and cerebral vascular reserve (CVR) were recorded and correlated with angiographic findings and clinical outcome. Results: Progression of ICA staging was noted in 23 sides (55.2%), and progression of PCA staging was noted in 18 sides (47.4%). Among the 18 cases of PCA stage progression, an associated decrease in LMC grade was noted in 12 sides (66.7%). These changes were associated with decreased regional CBF and CVR, which also explained the recurrent ischemic symptoms in 27.8% of these patients. In contrast, LMC grade increased in 15 (65.2%) sides of patients with ICA progression. Conclusions: Progressive steno-occlusive change in the PCA after revascularization is associated with a reduction in LMC blood flow and cerebral ischemia in moyamoya patients. This phenomenon might cause recurrent ischemic symptoms in 27.8% of patients.