| 1. |
- Behrens, Anders, et al.
(author)
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The Computerized General Neuropsychological INPH Test (CoGNIT) revealed improvement in Idiopathic Normal Pressure Hydrocephalus (INPH) after shunt surgery
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Other publication (other academic/artistic)abstract
- BackgroundWe have developed the COmputerized General Neuropsychological INPH Test (CoGNIT) dedicated for patients with idiopathic normal pressure hydrocephalus (INPH). Previously, validity and reliability of included tests have been established. The aim was to evaluate the battery’s sensitivity to detect cognitive changes after shunt surgery in INPH patients.MethodsPreoperatively, thirty-one INPH patients were given CoGNIT, which includes tests assessing memory, executive functions, attention, manual dexterity and psychomotor speed. CoGNIT also includes the Geriatric Depression Scale (GDS). Re-examination was done four months after shunt surgery. Scores and test completion were examined and compared to healthy elderly (n=44).ResultsPreoperative INPH test results were significantly lower in all tests compared to healthy. Improvements after shunt surgery were seen in all cognitive domains: memory (Ten-word list test, p<0,01), executive functions (Stroop incongruent, (p<0.05), attention (Two choice reaction test, p<0.01), psychomotor speed (Stroop congruent, p<0.05) and manual dexterity (Four- finger tapping, p<0.01). No ceiling effects were observed. Depressive symptoms were more common in INPH versus healthy and did not change postoperatively. Preoperatively 81 % of INPH patients completed at least eight of the nine included test.ConclusionsCoGNIT is sensitive to cognitive impairment and to investigate changes after shunt surgery in INPH. Completion rates are good. CoGNIT has a potential to be useful in the cognitive assessment of INPH.
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| 2. |
- Behrens, Anders, et al.
(author)
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The Computerized General Neuropsychological INPH Test revealed improvement in idiopathic normal pressure hydrocephalus after shunt surgery
- 2020
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In: Journal of Neurosurgery. - : AMER ASSOC NEUROLOGICAL SURGEONS. - 0022-3085 .- 1933-0693. ; 132:3, s. 733-740
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Journal article (peer-reviewed)abstract
- OBJECTIVE The Computerized General Neuropsychological INPH Test (CoGNIT) provides the clinician and the researcher with standardized and accessible cognitive assessments in patients with idiopathic normal pressure hydrocephalus (INPH). CoGNIT includes tests of memory, executive functions, attention, manual dexterity, and psychomotor speed. Investigations of the validity and reliability of CoGNIT have been published previously. The aim of this study was to evaluate CoGNIT's sensitivity to cognitive change after shunt surgery in patients with INPH.METHODS Forty-one patients with INPH (median Mini-Mental State Examination score 26) were given CoGNIT preoperatively and at a postoperative follow-up 4 months after shunt surgery. Scores were compared to those of 44 healthy elderly control volunteers. CoGNIT was administered by either a nurse or an occupational therapist.RESULTS Improvement after shunt surgery was seen in all cognitive domains: memory (10-word list test, p < 0.01); executive functions (Stroop incongruent color and word test, p < 0.01); attention (2-choice reaction test, p < 0.01); psychomotor speed (Stroop congruent color and word test, p < 0.01); and manual dexterity (4-finger tapping, p < 0.01). No improvement was seen in the Mini-Mental State Examination score. Preoperative INPH test scores were significantly impaired compared to healthy control subjects (p < 0.001 for all tests).CONCLUSIONS In this study the feasibility for CoGNIT to detect a preoperative impairment and postoperative improvement in INPH was demonstrated. CoGNIT has the potential to become a valuable tool in clinical and research work.
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| 3. |
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| 4. |
- Bovinder Ylitalo, Erik, 1985-
(author)
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Molecular heterogeneity of prostate cancer bone metastasis
- 2018
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Doctoral thesis (other academic/artistic)abstract
- Castration-resistant prostate cancer (CRPC) develops after androgen deprivation therapy of advanced PC, often with metastatic growth in bone. Patients with metastatic CRPC have very poor prognosis. Growth of CRPC, in most but not all patients, seems to involve androgen receptor (AR) activity, despite castrate levels of serum testosterone. Multiple mechanisms behind AR activation in castrated patients have been described, such as AR amplification, AR mutations, expression of constitutively active AR variants, and intra-tumoral steroid synthesis. However, other mechanisms beside AR activation are also involved and CRPC patients with tumors circumventing the need for AR stimulation will probably not benefit from AR targeting therapies but will need alternative treatments.Available treatments for CRPC are chemotherapy, AR antagonists or inhibition of androgen-synthesis. Novel drugs are constantly under development and several new therapies has recently been approved for clinical use. These include, in addition to new AR targeting therapies also immunotherapy, osteoclast inhibitors and bone-targeting radiopharmaceuticals. Due to heterogeneous mechanisms behind CRPC and that newly developed therapies are based on different mechanisms of action, there are reasons to believe that CRPC patients show different therapy responses due to diverse molecular properties of individual tumors. Although there are promising prospects, no biomarkers are used today for patient stratification into different treatments. Another important aspect is that, when effective, any therapy will probably induce tumor responses that subsequently cause further molecular diversities and alternative paths for development of tumor relapse and castration-resistance. Such mechanisms are important to understand in order to develop new treatment strategies.In this thesis, global gene expression and methylation patterns were studied in bone metastases obtained from PC patients going through metastasis surgery for spinal cord compression. Gene expression patterns were analyzed by multivariate statistics and ontology analysis with the aim to identify subgroups of biological/pathological relevance. Interesting findings from array analysis were verified using qRT-PCR and immunohistochemical analysis. In addition, a xenograft mouse model was used to study the effects of abiraterone (steroidogenesis inhibitor) and cabazitaxel (taxane), and subsequently developed resistance mechanisms in the 22Rv1 PC cell line expressing high levels of AR-V7; a constitutively active AR splice variant associated with a poor prognosis and resistance to AR targeting therapies.In summary, results showed that the majority of CRPC bone metastases were AR-driven, defined from high levels of AR-regulated gene transcripts, while a smaller sub-group was non-AR-driven (paper I). AR-driven bone metastases had high metabolic activity in combination with downregulated immune responses while non-AR-driven cases had a more pronounced immune response (paper I) and higher bone cell activity (paper II). Paper III identified pronounced hypermethylation in primary prostate tumors probably causing a suppressed anti-tumor immune-response whereas metastases showed a different methylation pattern related to increased AR activity and patient outcome. In paper IV, 22Rv1 xenografts showed poor response to abiraterone and initially excellent response to cabazitaxel, but eventually resistance occurred probably due to an upregulation of the ABCB1 transporter protein. Anti-androgens partly reversed the resistance.In conclusion, we have identified molecular heterogeneities in clinical bone metastases associated with biological characteristics, which could perhaps be used both for stratifying patients into treatment modalities, and to aid in further development of effective therapies for CRPC.
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| 5. |
- Kristensen, Jeppe A., et al.
(author)
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Background insect herbivory increases with local elevation but makes minor contribution to element cycling along natural gradients in the Subarctic
- 2020
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In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 10:20, s. 11684-11698
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Journal article (peer-reviewed)abstract
- Herbivores can exert major controls over biogeochemical cycling. As invertebrates are highly sensitive to temperature shifts (ectothermal), the abundances of insects in high-latitude systems, where climate warming is rapid, is expected to increase. In subarctic mountain birch forests, research has focussed on geometrid moth outbreaks, while the contribution of background insect herbivory (BIH) to elemental cycling is poorly constrained. In northern Sweden, we estimated BIH along 9 elevational gradients distributed across a gradient in regional elevation, temperature, and precipitation to allow evaluation of consistency in local versus regional variation. We converted foliar loss via BIH to fluxes of C, nitrogen (N), and phosphorus (P) from the birch canopy to the soil to compare with other relevant soil inputs of the same elements and assessed different abiotic and biotic drivers of the observed variability. We found that leaf area loss due to BIH was similar to 1.6% on average. This is comparable to estimates from tundra, but considerably lower than ecosystems at lower latitudes. The C, N, and P fluxes from canopy to soil associated with BIH were 1-2 orders of magnitude lower than the soil input from senesced litter and external nutrient sources such as biological N fixation, atmospheric deposition of N, and P weathering estimated from the literature. Despite the minor contribution to overall elemental cycling in subarctic birch forests, the higher quality and earlier timing of the input of herbivore deposits to soils compared to senesced litter may make this contribution disproportionally important for various ecosystem functions. BIH increased significantly with leaf N content as well as local elevation along each transect, yet showed no significant relationship with temperature or humidity, nor the commonly used temperature proxy, absolute elevation. The lack of consistency between the local and regional elevational trends calls for caution when using elevation gradients as climate proxies.
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| 6. |
- Lundkvist, B, et al.
(author)
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Cerebrospinal fluid hydrodynamics after placement of a shunt with an antisiphon device : a long-term study.
- 2001
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In: Journal of Neurosurgery. - : Journal of Neurosurgery Publishing Group (JNSPG). - 0022-3085 .- 1933-0693. ; 94:5, s. 750-6
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Journal article (peer-reviewed)abstract
- OBJECT: Few studies have been performed to investigate the cerebrospinal fluid (CSF) hydrodynamic profile in patients with idiopathic adult hydrocephalus syndrome (IAHS) before and after shunt implantation. The authors compared the in vivo CSF hydrodynamic properties, including the degree of gravity-induced CSF flow, of a shunt with an antisiphon device with a standard shunt.METHODS: Twelve patients with IAHS underwent insertion of shunts with Delta valves. Clinical testing, magnetic resonance imaging, and CSF hydrodynamic investigations were conducted with intracranial pressure (ICP), gravity effect, and pressure-flow curve of the shunt estimated at baseline and at 3 and 12 months postoperatively. No shunt was revised. Despite postoperative clinical improvement in all patients who received Delta valves, the mean ICP was only moderately reduced (mean decrease at 3 months 0.3 kPa [p = 0.02], at 12 months 0.2 kPa [not significant]). Patients with the greatest increase in ICP preoperatively had the most pronounced decrease postoperatively. The hydrostatic effect of the Delta valves was significantly lower than with the Hakim shunts (0.1-0.2 kPa compared with 0.6 kPa). The increased conductance (that is, lowered resistance) was up to 14 times higher with the Delta valves compared with preoperative levels.CONCLUSIONS: The function of a CSF shunt may be more complicated than previously thought; the subcutaneous pressure acting on the antisiphon device can modify the shunt characteristics. A compensatory increase in CSF production may counteract the increased outflow through the shunt. The improved CSF outflow conductance may increase the intracranial compliance and thereby dampen a pathological ICP waveform.
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| 7. |
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| 8. |
- Malm, Jan, et al.
(author)
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Implementation of a new CSF dynamic device: a multicenter feasibility study in 562 patients
- 2012
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In: Acta Neurologica Scandinavica. - : John Wiley and Sons. - 0001-6314 .- 1600-0404. ; 125:3, s. 199-205
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Journal article (peer-reviewed)abstract
- Objectives - The cerebrospinal fluid (CSF) infusion test is frequently used when selecting hydrocephalus patients for shunt surgery. Very little has been reported regarding adverse events. We present a prospective feasibility study. Methods -Standardized devices for measuring CSF dynamics were built and 562 patients investigated: Needles were placed by lumbar puncture (LP). An automatic CSF infusion protocol was performed. Course of events during the investigation as well as adverse events were registered. Results Preoperative evaluation of normal-pressure hydrocephalus was the most common indication (63%), followed by evaluation of shunt function (23%) and intracranial pressure recordings (14%). The LP was successfully performed in all but nine cases with 24 patients (4.3%) reporting major discomfort. Ringer infusion was performed in 474 investigations, and a valid measurement of the outflow resistance was received in 439 (93%). During the infusion phase, 17 (4%) patients reported severe headache. Infusion volume was significantly higher in patients having subjective symptoms during the infusion phase compared with those without adverse events. During 269 preoperative CSF tap tests, six (2%) patients had severe headache. Postinvestigational headache was reported by 83 (15%) patients at the 24-h follow-up. No serious adverse events were observed. Conclusion Infusion testing was safe and without serious adverse events with a high rate of successful procedures. The investigation was associated with expected mild to moderate discomfort.
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| 9. |
- Metcalfe, Daniel B., et al.
(author)
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Patchy field sampling biases understanding of climate change impacts across the Arctic
- 2018
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In: Nature Ecology and Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 2:9, s. 1443-1448
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Journal article (peer-reviewed)abstract
- Effective societal responses to rapid climate change in the Arctic rely on an accurate representation of region-specific ecosystem properties and processes. However, this is limited by the scarcity and patchy distribution of field measurements. Here, we use a comprehensive, geo-referenced database of primary field measurements in 1,840 published studies across the Arctic to identify statistically significant spatial biases in field sampling and study citation across this globally important region. We find that 31% of all study citations are derived from sites located within 50 km of just two research sites: Toolik Lake in the USA and Abisko in Sweden. Furthermore, relatively colder, more rapidly warming and sparsely vegetated sites are under-sampled and under-recognized in terms of citations, particularly among microbiology-related studies. The poorly sampled and cited areas, mainly in the Canadian high-Arctic archipelago and the Arctic coastline of Russia, constitute a large fraction of the Arctic ice-free land area. Our results suggest that the current pattern of sampling and citation may bias the scientific consensuses that underpin attempts to accurately predict and effectively mitigate climate change in the region. Further work is required to increase both the quality and quantity of sampling, and incorporate existing literature from poorly cited areas to generate a more representative picture of Arctic climate change and its environmental impacts.
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| 10. |
- Nyholm, Tufve, et al.
(author)
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A national approach for automated collection of standardized and population-based radiation therapy data in Sweden
- 2016
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In: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 119:2, s. 344-350
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Journal article (peer-reviewed)abstract
- Purpose: To develop an infrastructure for structured and automated collection of interoperable radiation therapy (RT) data into a national clinical quality registry. Materials and methods: The present study was initiated in 2012 with the participation of seven of the 15 hospital departments delivering RT in Sweden. A national RT nomenclature and a database for structured unified storage of RT data at each site (Medical Information Quality Archive, MIQA) have been developed. Aggregated data from the MIQA databases are sent to a national RT registry located on the same IT platform (INCA) as the national clinical cancer registries. Results: The suggested naming convention has to date been integrated into the clinical workflow at 12 of 15 sites, and MIQA is installed at six of these. Involvement of the remaining 3/15 RT departments is ongoing, and they are expected to be part of the infrastructure by 2016. RT data collection from ARIA (R), Mosaiq (R), Eclipse (TM), and Oncentra (R) is supported. Manual curation of RT-structure information is needed for approximately 10% of target volumes, but rarely for normal tissue structures, demonstrating a good compliance to the RT nomenclature. Aggregated dose/volume descriptors are calculated based on the information in MIQA and sent to INCA using a dedicated service (MIQA2INCA). Correct linkage of data for each patient to the clinical cancer registries on the INCA platform is assured by the unique Swedish personal identity number. Conclusions: An infrastructure for structured and automated prospective collection of syntactically inter operable RT data into a national clinical quality registry for RT data is under implementation. Future developments include adapting MIQA to other treatment modalities (e.g. proton therapy and brachytherapy) and finding strategies to harmonize structure delineations. How the RT registry should comply with domain-specific ontologies such as the Radiation Oncology Ontology (ROO) is under discussion.
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