The carbon offset problem and how SMEs should approach it! A qualitative analysis of carbon offset strategies for SMEs in the Netherlands.

Small and medium-sized enterprises (SMEs) often lack the resources and knowledge to navigate the voluntary carbon offset market (COM), which is characterized by uncertainty, unclear regulations, and opaque practices. However, as SMEs account for a large share of global emissions, it is crucial to encourage and enable them to take actions to reduce their carbon footprint. This thesis aims to provide SMEs with a better understanding of carbon offsetting, the problems associated with it, and how to choose the most effective strategy. The thesis includes a literature review of the background of Carbon Dioxide (CO2) offsetting, including the different types of CO2 markets and the history of mandatory and voluntary carbon offset policies. The expected future of carbon offset policies is also discussed. Carbon offsetting has been developed as a market-based mechanism to reduce Greenhouse Gas (GHG) emissions. It allows companies and individuals to offset their own emissions by investing in projects that reduce emissions elsewhere. There are two types of carbon markets, namely mandatory and voluntary. Mandatory carbon markets are implemented through government regulations, while the voluntary carbon market (VCM) is driven by companies and individuals who choose to offset their emissions voluntarily. The history of mandatory carbon offset policies can be traced back to the Kyoto Protocol, which established the Clean Development Mechanism (CDM). This mechanism allowed developed countries to offset their emissions by investing in emissions reduction projects in developing countries. However, there were many issues with the CDM, such as the potential for double counting and the lack of additionality (projects financed with offset funds that would also happen without these funds). Voluntary carbon offset policies have been developed by companies and individuals who wish to reduce their carbon footprint voluntarily. This market has grown rapidly in recent years, but it is characterized by a lack of transparency and regulation, making it difficult for SMEs to navigate. The potential risks associated with voluntary carbon offsetting include the quality and sustainability of offset projects, non-additionality, and the potential negative impacts on environments and people located near the offset projects. To address the challenges associated with carbon offsetting for SMEs, this thesis uses the multi-criteria decision analysis (MCDA) framework to evaluate and select the most appropriate carbon offsetting strategy. The MCDA model is based on the identification of key decision criteria, including cost, transparency, and environmental impact, as well as the development of weightings and scoring for each criterion. The thesis concludes with recommendations for SMEs to address the challenges of carbon offsetting, such as engaging in due diligence, verifying the quality of offset projects, and considering the long-term sustainability of their offsetting strategy. The proposed MCDA framework can be used by SMEs to evaluate their carbon offsetting options and select the most appropriate strategy based on their specific needs and priorities. In conclusion, this thesis provides SMEs with a better understanding of the COM, the challenges associated with carbon offsetting, and how to choose the most effective strategy. The proposed MCDA framework can assist SMEs in making informed decisions about their carbon offsetting practices, leading to a more sustainable and environmentally responsible business ecosystem

MR imaging of the brachial plexus

In this retrospective study we describe the MR imaging findings in 230 consecutive patients with suspected pathology in or near the brachial plexus. These patients were studied from 1991 through to 1996. Chapter 2 describes the anatomy and the MR imaging techniques. As the anatomy of the brachial plexus and the related structures is quite complicated, we eventually use as protocol of choice a 3D volume acquisition for the best understanding of this complex anatomy. The advantages of this 3D volume acquisition are, besides the use of thin overlapping slices, the MPR and cine-display viewing mode possibilities. The use of thin slices (2 mm) provides excellent anatomical detail. The following anatomic details can be discerned: the individual ventral rami of the nerve roots, the three trunks, the three cords and the stellate ganglion. The overlapped images can be reconstructed in any plane with the same image quality, and the use of the cine-display viewing mode affords a better insight into the continuity of the nerves and vessels. In our experience, the use of a 3D volume acquisition markedly improves the understanding of the normal anatomy of the brachial plexus on MR imaging and can possibly better delineate the pathology involving the brachial plexus. Chapter 3 mainly deals with the tumors we have found in or near the brachial plexus. In this chapter we also describe a group of patients alleged to have a tumor, but where no tumor was found. The first group consists of 66 patients where a tumor in or near the brachial plexus was found with MR imaging. We found 10 neurogenic tumors (five schwannomas, one neurofibroma, two malignant schwannomas and two without a histological diagnosis). These tumors show characteristic MR imaging findings: a low signal intensity on the T1-weighted images, an increased signal intensity on the proton-density images, a high signal intensity on the T2-weighted images, enhancement after administration of gadolinium-DTPA, a fusiform growth, a sharply defined edge, and the involved nerve can often be found entering and leaving the tumor. These specific imaging characteristics applied to nine of these 10 tumors. Besides these 10 Chapter 7 Summary and Conclusions?102 Chapter 7 neurogenic tumors, we describe 56 non-neurogenic tumors: lung tumor (n=24), metastasis of breast carcinoma (n=9), metastasis of other tumors (n=8), B-cell non-Hodgkins lymphoma (n=2), leiomyosarcoma (n=1), liposarcoma (n=1), chondrosarcoma (n=2), synoviosarcoma (n=1), aggressive fibromatosis (n=2), meningocele (n=1), lipoma (n=3), a hematoma in a neck cyst (n=1), and one tumor of unknown origin. In the preoperative evaluation of tumors near the brachial plexus, the 3D volume acquisition provides the radiologists and the surgeons with better insight into the precise extension of the tumor. MR imaging could delineate the extension of these tumors well, and determine whether or not there was brachial plexus involvement. The second group consists of 70 patients where no tumor was detected with MR imaging. Three patients had an infection, 17 patients were imaged after radiation therapy and had no signs of tumor recurrence, and 50 patients had normal MR imaging findings. Chapter 4 discusses the value of MR imaging in patients with brachial plexopathy after trauma and in patients with thoracic outlet syndromes. We found 31 abnormal MR imaging investigations in patients with a history of trauma. Ten of these patients presented with a flail arm after a severe accident, in most cases a motorcycle accident. In five of these patients an additional 3D-TSE sequence of the C-spine was done in order to visualize traumatic nerve root avulsions and traumatic meningoceles. Abnormalities we found in this group were thickening of the brachial plexus, hematoma, and a clavicle fracture with compression of the brachial plexus. We were not able to visualize a rupture of the brachial plexus, nor visualize all the nerve root avulsions. Abnormalities we found in the remaining 21 patients included clavicle fractures with suspected brachial plexus compression (n=14), traumatic meningoceles in patients with known nerve root avulsions to exclude neuroma formation (n=3), a stab wound (n=1), a coracoid process fracture (n=1), a battered child (n=1) and a shoulder luxation (n=1). In 18 patients with a history of trauma MR imaging was normal. Two of these patients were operated upon and appeared to have a rupture of a part of the brachial plexus. We conclude that MR imaging is not very good at predicting the surgical findings in cases of brachial plexus rupture or nerve root avulsions. MR imaging can be helpful in demonstrating brachial plexus compression by a hematoma or a clavicle fracture with callus formation. In this chapter we also describe a group of 23 patients with a wide variety of symptoms, which could be due to a thoracic outlet syndrome. In three patients a cervical rib was present, two patients had had a cervical rib removal previously. In one patient, who had the typical true neurogenic thoracic outlet syndrome, a slight angulation of the ventral ramus of root C8 was seen, which appeared to be due to a fibrous band at surgery. Most patients did not show any abnormalities with MR imaging. We were?Summary and Conclusions 103 not able to demonstrate a fibrous band with MR imaging. We conclude that MR imaging in patients with a thoracic outlet syndrome is not very useful, except for serving to exclude other structural abnormalities. Chapter 5 describes the MR imaging appearance of radiation-induced brachial plexopathy. MR imaging was performed in two patients with the clinical diagnosis of radiation-induced brachial plexopathy and in one with surgically proven radiation fibrosis of the brachial plexus. Three patients who had had radiation therapy to the axilla and supraclavicular region (two with breast carcinoma and one with Hodgkins lymphoma) presented with symptoms of the arm and hand. To exclude metastases or tumor recurrence MR imaging was performed. In one patient, fibrosis showing low signal intensity was found, while in two patients high signal intensity fibrosis surrounding the brachial plexus was found on the T2-weighted images. In one case gadolinium-DTPA enhancement of the fibrosis 21 years after radiation therapy was seen. We conclude that radiation-induced brachial plexopathy can have different MR imaging appearances. We found that radiation fibrosis can have both low and high signal intensities on T2-weighted images, and that fibrosis can enhance even decades after radiation therapy. In Chapter 6 we studied whether MR imaging of the brachial plexus is useful to distinguish multifocal motor neuropathy (MMN) from lower motor neuron disease (LMND) and whether abnormalities resemble those of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). MMN is a potentially treatable pure motor neuropathy which clinically resembles LMND. Both diseases are characterized by progressive asymmetric weakness of the limbs and muscular atrophy without sensory symptoms. CIDP is a symmetric polyneuropathy which affects both motor and sensory fibers. Both CIDP and MMN are probably immune-mediated neuropathies, as autoantibodies to peripheral nerve myelin have been found. We compared MR imaging scans of the brachial plexus from nine patients with MMN with scans from five patients with CIDP, eight patients with LMND, and 174 controls. In two patients with MMN, and in three patients with CIDP, the MR imaging scans showed an increased signal intensity on the T2-weighted images of the brachial plexus. Two other patients with MMN demonstrated a more focal increased signal intensity on the T2-weighted images, in one patient only in the axilla, and in one patient in the axilla and in the ventral rami of the roots. MR imaging of the brachial plexus of eight patients with LMND was normal. The distribution of the MR imaging abnormalities corresponded with the distribution of symptoms of the patients: asymmetrical in MMN and symmetrical in CIDP. These findings demonstrate that MR imaging abnormalities of the brachial plexus in patients with MMN resemble those seen in CIDP and may be useful to distinguish MMN from LMND.?104 Chapter

Congenital tracheobronchomegaly (Mounier-Kuhn syndrome) in a 28-year-old Zambian male: a case report

Congenital tracheobronchomegaly, also known as Mounier Kuhn Syndrome (MKS) is a rare respiratory disorder characterized by dilatation of the trachea and bronchi. We report a case of a 28-year-old male of African descent in Zambia, who presented with a history of chronic productive cough and repeated chest infections since childhood. He had been treated numerous times for lower respiratory tract infections, and had received empiric tuberculosis (TB) treatment based on chest radiograph findings, despite negative sputum microscopy and molecular tests for TB. Investigations revealed normal baseline blood results and sputum results. He however had markedly increased levels of serum immunoglobulin E. and spirometry showed an obstructive pattern with significant post bronchodilator improvement. High-resolution computed tomography scan revealed tracheal dilatation, extensive bilateral bronchiectasis and tracheal and bronchial diverticula. The latter were also seen on bronchoscopy, confirming the diagnosis of Mounier-Kuhn syndrome. The patient was treated with combined inhaled corticosteroids and bronchodilators, as well as chest physiotherapy for mucus clearance, which led to improvement in his symptoms. Our case highlights how in low-resource settings, chronic lung diseases, particularly bronchiectasis, are often clinically and radiologically mistaken for and presumptively treated as TB (or its sequelae). Mounier-Kuhn syndrome, albeit rare, should be considered in the differential diagnosis of patients with recurrent lower respiratory tract infections or bronchiectasis. Multidisciplinary team meetings can help in the diagnosis of rare lung diseases

Repeated Endovascular Thrombectomy in Patients With Acute Ischemic Stroke: Results From a Nationwide Multicenter Database

Background and Purpose- Patients with acute ischemic stroke treated with endovascular thrombectomy may be treated with repeat endovascular thrombectomy (rEVT) in case of recurrent large vessel occlusion. Data on safety and efficacy of these interventions is scarce. Our aim is to report on frequency, timing, and outcome of rEVT in a large nation-wide multicenter registry. Methods- In the Netherlands, all patients with endovascular thrombectomy have been registered since 2002 (MR CLEAN Pretrial registry, MR CLEAN Trial [Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands], and MR CLEAN Registry). We retrospectively reviewed these databases for anterior circulation rEVT cases. Patient characteristics, procedural data, and functional outcome (modified Rankin Scale at 90 days) were analyzed. Results- Of 3928 patients treated between 2002 and 2017, 27 (0.7%) underwent rEVT. Median time between first and second procedure was 78 (1-1122) days; 11/27 patients were re-treated within 30 days. Cardioembolism was the most common etiology (18 patients [67%]). In 19 patients (70%), recurrent occlusion occurred ipsilateral to previous occlusion. At 90 days after rEVT procedure, 44% of the patients had achieved functional independence (modified Rankin Scale score of 0-2), and 33% had died. Adverse events were 2/27 (7.4%) intracranial hemorrhage, 1/27 (3.7%) stroke progression, and 1/27 (3.7%) pneumonia. Conclusions- In this large nationwide cohort of patients with acute ischemic stroke treated with endovascular thrombectomy, rEVT was rare. Stroke cause was mainly cardio-embolic, and most recurrent large vessel occlusions in which rEVT was performed occurred ipsilateral. Although there probably is a selection bias on repeated treatment in case of recurrent large vessel occlusion, rEVT appears safe, with similar outcome as in single-treated cases

A cluster of blood-based protein biomarkers associated with decreased cerebral blood flow relates to future cardiovascular events in patients with cardiovascular disease

Biological processes underlying decreased cerebral blood flow (CBF) in patients with cardiovascular disease (CVD) are largely unknown. We hypothesized that identification of protein clusters associated with lower CBF in patients with CVD may explain underlying processes. In 428 participants (74% cardiovascular diseases; 26% reference participants) from the Heart-Brain Connection Study, we assessed the relationship between 92 plasma proteins from the Olink® cardiovascular III panel and normal-appearing grey matter CBF, using affinity propagation and hierarchical clustering algorithms, and generated a Biomarker Compound Score (BCS). The BCS was related to cardiovascular risk and observed cardiovascular events within 2-year follow-up using Spearman correlation and logistic regression. Thirteen proteins were associated with CBF (ρSpearman range: −0.10 to −0.19, pFDR-corrected &lt;0.05), and formed one cluster. The cluster primarily reflected extracellular matrix organization processes. The BCS was higher in patients with CVD compared to reference participants (pFDR-corrected &lt;0.05) and was associated with cardiovascular risk (ρSpearman 0.42, p &lt; 0.001) and cardiovascular events (OR 2.05, p &lt; 0.01). In conclusion, we identified a cluster of plasma proteins related to CBF, reflecting extracellular matrix organization processes, that is also related to future cardiovascular events in patients with CVD, representing potential targets to preserve CBF and mitigate cardiovascular risk in patients with CVD.</p

Imaging strategies for detection of urgent conditions in patients with acute abdominal pain: diagnostic accuracy study

Objective To identify an optimal imaging strategy for the accurate detection of urgent conditions in patients with acute abdominal pain

UNC13A in amyotrophic lateral sclerosis: from genetic association to therapeutic target

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options and an incompletely understood pathophysiology. Although genomewide association studies (GWAS) have advanced our understanding of the disease, the precise manner in which risk polymorphisms contribute to disease pathogenesis remains unclear. Of relevance, GWAS have shown that a polymorphism (rs12608932) in the UNC13A gene is associated with risk for both ALS and frontotemporal dementia (FTD). Homozygosity for the C-allele at rs12608932 modifies the ALS phenotype, as these patients are more likely to have bulbar-onset disease, cognitive impairment and FTD at baseline as well as shorter survival. UNC13A is expressed in neuronal tissue and is involved in maintaining synaptic active zones, by enabling the priming and docking of synaptic vesicles. In the absence of functional TDP-43, risk variants in UNC13A lead to the inclusion of a cryptic exon in UNC13A messenger RNA, subsequently leading to nonsense mediated decay, with loss of functional protein. Depletion of UNC13A leads to impaired neurotransmission. Recent discoveries have identified UNC13A as a potential target for therapy development in ALS, with a confirmatory trial with lithium carbonate in UNC13A cases now underway and future approaches with antisense oligonucleotides currently under consideration. Considering UNC13A is a potent phenotypic modifier, it may also impact clinical trial outcomes. This present review describes the path from the initial discovery of UNC13A as a risk gene in ALS to the current therapeutic options being explored and how knowledge of its distinct phenotype needs to be taken into account in future trials

Outcome Prediction Models for Endovascular Treatment of Ischemic Stroke:Systematic Review and External Validation

BACKGROUND AND PURPOSE: Prediction models for outcome of patients with acute ischemic stroke who will undergo endovascular treatment have been developed to improve patient management. The aim of the current study is to provide an overview of preintervention models for functional outcome after endovascular treatment and to validate these models with data from daily clinical practice. METHODS: We systematically searched within Medline, Embase, Cochrane, Web of Science, to include prediction models. Models identified from the search were validated in the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) registry, which includes all patients treated with endovascular treatment within 6.5 hours after stroke onset in the Netherlands between March 2014 and November 2017. Predictive performance was evaluated according to discrimination (area under the curve) and calibration (slope and intercept of the calibration curve). Good functional outcome was defined as a score of 0–2 or 0–3 on the modified Rankin Scale depending on the model. RESULTS: After screening 3468 publications, 19 models were included in this validation. Variables included in the models mainly addressed clinical and imaging characteristics at baseline. In the validation cohort of 3156 patients, discriminative performance ranged from 0.61 (SPAN-100 [Stroke Prognostication Using Age and NIH Stroke Scale]) to 0.80 (MR PREDICTS). Best-calibrated models were THRIVE (The Totaled Health Risks in Vascular Events; intercept −0.06 [95% CI, −0.14 to 0.02]; slope 0.84 [95% CI, 0.75–0.95]), THRIVE-c (intercept 0.08 [95% CI, −0.02 to 0.17]; slope 0.71 [95% CI, 0.65–0.77]), Stroke Checkerboard score (intercept −0.05 [95% CI, −0.13 to 0.03]; slope 0.97 [95% CI, 0.88–1.08]), and MR PREDICTS (intercept 0.43 [95% CI, 0.33–0.52]; slope 0.93 [95% CI, 0.85–1.01]). CONCLUSIONS: The THRIVE-c score and MR PREDICTS both showed a good combination of discrimination and calibration and were, therefore, superior in predicting functional outcome for patients with ischemic stroke after endovascular treatment within 6.5 hours. Since models used different predictors and several models had relatively good predictive performance, the decision on which model to use in practice may also depend on simplicity of the model, data availability, and the comparability of the population and setting

Determinants of Symptomatic Intracranial Hemorrhage After Endovascular Stroke Treatment:A Retrospective Cohort Study

Background: Symptomatic intracranial hemorrhage (sICH) is a serious complication after endovascular treatment for ischemic stroke. We aimed to identify determinants of its occurrence and location. Methods: We retrospectively analyzed data from the Dutch MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and MR CLEAN registry. We included adult patients with a large vessel occlusion in the anterior circulation who underwent endovascular treatment within 6.5 hours of stroke onset. We used univariable and multivariable logistic regression analyses to identify determinants of overall sICH occurrence, sICH within infarcted brain tissue, and sICH outside infarcted brain tissue. Results: SICH occurred in 203 (6%) of 3313 included patients and was located within infarcted brain tissue in 50 (25%), outside infarcted brain tissue in 23 (11%), and both within and outside infarcted brain tissue in 116 (57%) patients. In 14 patients (7%), data on location were missing. Prior antiplatelet use, baseline systolic blood pressure, baseline plasma glucose levels, post-endovascular treatment modified treatment in cerebral ischemia score, and duration of procedure were associated with all outcome parameters. In addition, determinants of sICH within infarcted brain tissue included history of myocardial infarction (adjusted odds ratio, 1.65 [95% CI, 1.06-2.56]) and poor collateral score (adjusted odds ratio, 1.42 [95% CI, 1.02-1.95]), whereas determinants of sICH outside infarcted brain tissue included level of occlusion on computed tomography angiography (internal carotid artery or internal carotid artery terminus compared with M1: adjusted odds ratio, 1.79 [95% CI, 1.16-2.78]). Conclusions: Several factors, some potentially modifiable, are associated with sICH occurrence. Further studies should investigate whether modification of baseline systolic blood pressure or plasma glucose level could reduce the risk of sICH. In addition, determinants differ per location of sICH, supporting the hypothesis of varying underlying mechanisms. Registration: URL: https://www.isrctn.com/; Unique identifier: ISRCTN10888758