Creating new littoral zones in a shallow lake to forward-restore an aquatic food web.

Current rates of habitat loss require science-based predictions on how to restore or newly create lost habitat types. In aquatic ecosystems, littoral zones are key habitats for food web functioning, but they are often replaced by unnatural steep shorelines for water safety. To reverse this trend, knowledge is needed on how to successfully (re)create littoral zones. We quantified the response of an aquatic food web to the large-scale creation of new heterogeneous littoral habitats in shallow lake Markermeer, the Netherlands. Lake Markermeer was formed by dike construction in a former estuary, which created a heavily modified homogeneous 70,000 ha turbid lake lacking littoral habitat. Fish and bird populations declined over the last decades, but classical restoration via return to former marine conditions would compromise water safety and the large spatial scale prohibited biodiversity offsets. Therefore, an innovative "forward-looking restoration" approach was adopted: a 1000 ha archipelago called "Marker Wadden" was constructed without using a historic reference situation to return to. This aimed bottom-up stimulation of the aquatic food web by adding missing gradual land-water transitions and sheltered waters to the lake. After four years, new sheltered shorelines had become vegetated if they were constructed from nutrient-rich sediments. Exposed and sandy shorelines remained free of vegetation. Zooplankton community diversity increased in sheltered waters due to bottom-up processes, which increased food availability for higher trophic levels, including young fish. The creation of sheltered waters increased macroinvertebrate densities threefold, with sediment type determining the community composition. The archipelago became new nursery habitat for 13 of the 24 fish species known to occur in the lake, with up to 10-fold higher abundances under sheltered conditions. We conclude that modifying abiotic conditions can stimulate multiple trophic levels in aquatic food webs simultaneously, even in heavily modified ecosystems. This provides proof-of-principle for the forward-looking restoration approach.

The additional value of weight-bearing and gravity stress ankle radiographs in determining stability of isolated type B ankle fractures.

GOAL: The aim of this study is to investigate whether weight-bearing and gravity stress radiographs have additional value in predicting concomitant deep deltoid ligamentous (DDL) injury in case of isolated Weber type B fibular fractures. This may help to make the clinically relevant distinction between unstable fractures and fractures that can be treated conservatively. METHODS: In this prospective cohort study, 90 patients with an isolated type B ankle fracture, without a medial or posterior fracture, and a medial clear space (MCS) < 6 mm on the regular mortise (RM) view were included. In all patients, an additional gravity stress (GS) view and an MRI scan were performed. Furthermore, in 51 patients, an additional weight-bearing (WB) radiograph was performed. The MCS and superior clear space (SCS) measurements of these radiographs were compared with MRI findings to measure sensitivity and specificity in excluding deep deltoid ligament (DDL) rupture. RESULTS: The mean MCS on the RM view was 3.32 mm (1.73-5.93) compared to 4.75 mm (2.33-10.40) on the GS view and 3.18 mm (1.93-6.9) on the WB radiograph. MRI showed a high-grade or complete deltoid ligament tear in 25 (28%) patients. Using an MCS cut-off value of ≥ SCS + 2 mm, the RM view showed 0% sensitivity and 97% specificity in diagnosing a DDL rupture. Both the GS view (with MCS ≥ SCS + 3 mm as cut-off value) and the WB radiograph (with cut-off value MCS ≥ SCS + 2 mm) showed 6% sensitivity and 100% specificity. CONCLUSION: The gravity stress and weight-bearing radiograph can accurately exclude DDL injury. They might have extra value in addition to the conventional mortise view in assessing the stability of isolated type B ankle fractures. This helps in deciding whether patients should be selected for operative or safe conservative treatment.

The value of radiologic diagnostics in evaluating deltoid integrity in isolated type B ankle fractures: a systematic review of the literature.

INTRODUCTION: Excluding deep deltoid ligament (DDL) rupture in isolated type B ankle fractures is crucial in the decision-making process for surgical or conservative treatment. There is no consensus about the most accurate radiologic diagnostic test to determine medial injury. The aim of this study is to systematically review the literature concerning radiologic diagnostics that evaluate medial injury in adult patients with isolated type B ankle fractures. METHODS: The electronic databases PubMed, Embase, Web of Science, COCHRANE Library, and Emcare were searched to identify studies published from January 1990 to December 2020 concerning sensitivity and specificity of diagnostic tests that evaluate medial injury in patients with an isolated type B ankle fracture. For inclusion, comparison to a reference test was required to provide results in terms of sensitivity, specificity, and preferably positive predictive value and negative predictive value RESULTS: This review included 8 studies. Ultrasound showed the highest sensitivity of 100% and a specificity between 90 and 100% for detecting DDL rupture. Gravity stress radiographs showed a sensitivity of 71-100% and a specificity between 88 and 92%. The mortise, external rotation stress test, and MRI had lower sensitivity and specificity values, between 65 and 88%. CONCLUSION: The most accurate and available methods for diagnosing deltoid integrity seem to be the ultrasound and the GS radiograph. Further research is needed to confirm the results of this review.

Fibular displacement does not predict instability in type B ankle fractures.

INTRODUCTION: Despite the wide prevalence of ankle fractures, no consensus exists on the most accurate radiologic diagnostic tool to indicate medial ligament injury in isolated type B distal fibular fractures. The aim of this study was to evaluate the value of the fibular fracture displacement in predicting medial clear space widening on the gravity stress radiographs, as a parameter of fracture instability. METHODS: This retrospective cohort study included 192 patients with an isolated type B fibular fracture, for which a regular mortise and gravity stress radiograph were made in our hospital between January 2014 and December 2019. On the regular mortise and lateral radiographs, the medial clear space (MCS), superior clear space (SCS), anteroposterior and lateral fibular displacement were measured. On the gravity stress radiograph, the MCS and SCS were measured. Instability was defined as MCS ≥ SCS + 3.0 mm on the gravity stress radiograph. A receiver operating characteristic (ROC) curve was constructed to evaluate the predictive value of the fibular displacement. RESULTS: Of the 192 included patients, 55 (29%) patients had instable ankle fractures. In predicting instability, fibular displacement demonstrated an area under the curve (AUC) of 0.68 (95% confidence interval 0.60-0.77) and a correlation coefficient of 0.41 with MCS. CONCLUSION: Fibular displacement on regular mortise view is a poor predictor of instability in type B fibular fractures. It should not be advised to use the fracture displacement as parameter for medial injury and thus for operative treatment.

A self-matched leaky-wave antenna for ultrahigh-field magnetic resonance imaging with low specific absorption rate.

The technology of magnetic resonance imaging is developing towards higher magnetic fields to improve resolution and contrast. However, whole-body imaging at 7 T or even higher flux densities remains challenging due to wave interference, tissue inhomogeneities, and high RF power deposition. Nowadays, proper RF excitation of a human body in prostate and cardiac MRI is only possible to achieve by using phased arrays of antennas attached to the body (so-called surface coils). Due to safety concerns, the design of such coils aims at minimization of the local specific absorption rate (SAR), keeping the highest possible RF signal in the region of interest. Most previously demonstrated approaches were based on resonant structures such as e.g. dipoles, capacitively-loaded loops, TEM-line sections. In this study, we show that there is a better compromise between the transmit signal [Formula: see text] and the local SAR using non-resonant surface coils generating a low electric field in the proximity of their conductors. With this aim, we propose and experimentally demonstrate a leaky-wave antenna implemented as a periodically-slotted microstrip transmission line. Due to its non-resonant radiation, it induces only slightly over half the peak local SAR compared to a state-of-the-art dipole antenna but has the same transmit efficiency in prostate imaging at 7 T. Unlike other antennas for MRI, the leaky-wave antenna does not require to be tuned and matched when placed on a body, which makes it easy-to-use in prostate imaging at 7 T MRI.

Functional connectivity network between terrestrial and aquatic habitats by a generalist waterbird, and implications for biovectoring.

Birds are vectors of dispersal of propagules of plants and other organisms including pathogens, as well as nutrients and contaminants. Thus, through their movements they create functional connectivity between habitat patches. Most studies on connectivity provided by animals to date have focused on movements within similar habitat types. However, some waterbirds regularly switch between terrestrial, coastal and freshwater habitats throughout their daily routines. Lesser black-backed gulls that overwinter in Andalusia use different habitat types for roosting and foraging. In order to reveal their potential role in biovectoring among habitats, we created an inter-habitat connectivity network based on GPS tracking data. We applied connectivity measures by considering frequently visited sites as nodes, and flights as links, to determine the strength of connections in the network between habitats, and identify functional units where connections are more likely to happen. We acquired data for 42 tagged individuals (from five breeding colonies), and identified 5676 direct flights that connected 37 nodes. These 37 sites were classified into seven habitat types: reservoirs, natural lakes, ports, coastal marshes, fish ponds, rubbish dumps and ricefields. The Doñana ricefields acted as the central node in the network based on centrality measures. Furthermore, during the first half of winter when rice was harvested, ricefields were the most important habitat type in terms of total time spent. Overall, 90% of all direct flights between nodes were between rubbish dumps (for foraging) and roosts in other habitats, thereby connecting terrestrial and various wetland habitats. The strength of connections decreased between nodes as the distance between them increased, and was concentrated within ten independent spatial and functional units, especially between December and February. The pivotal role for ricefields and rubbish dumps in the network, and their high connectivity with aquatic habitats in general, have important implications for biovectoring into their surroundings.

Proposal for a National Blueprint Framework to Monitor Progress on Water-Related Sustainable Development Goals in Europe.

The 17 Sustainable Development Goals (SDGs) underpinned by 169 targets presents national governments with huge challenges for implementation. We developed a proposal for a National Blueprint Framework (NBF) with 24 water-related indicators, centered on SDG 6 (clean water and sanitation for all), each with a specific target. We applied the NBF to 28 EU Member States (EU-28) and conclude that: (1) The current SDG 6 indicators are useful for monitoring progress toward water-related targets but their usefulness can be improved by focusing more on their practical implementation. (2) The extension of SDG 6 with complementary indicators (e.g. for the circular economy of water) and quantitative policy targets is urgently needed. This will benefit the communication process and progress at the science-policy interface. (3) SDG indicators can be improved in a SMART (specific, measurable, achievable, relevant, and time-bound) manner and by setting clear policy targets for each indicator, allowing for measuring distance-to-targets. This allows country-to-country comparison and learning, and accelerates the SDG implementation process. (4) We propose 24 water-related indicators centered on SDG 6, with complementary indicators including quantitative policy targets. The approach is doable, easily scalable, and flexibly deployable by collecting information for the EU-28. (5) Main gaps in the EU-28 are observed for water quality, wastewater treatment, nutrient, and energy recovery, as well as climate adaptation to extreme weather events (heat, droughts, and floods). (6) The framework was less successful for non-OECD countries due to lack of data and EU-centric targets for each indicator. This needs further research.

Long-term outcome in operatively and non-operatively treated isolated type B fibula fractures.

PURPOSE: Type B fibula fractures are the most common type of ankle fractures. Generally, surgical repair is advised for unstable fractures and non-operative treatment for stable fractures. However, evidence on long-term functional outcome of both treatment regimens is lacking. Aim of this study is to compare the long-term outcome in function and pain between patients with an isolated type B fibula fracture treated non-operatively and surgically. MATERIAL & METHODS: In this retrospective cohort study, all consecutive patients aged between 18 and 75 years, treated non-operatively or surgically between January 2008 and December 2015 for a distal fibula fracture at the level of the syndesmosis without an additional medial or posterior fracture and with a medial clear space ≤6 mm were included. All eligible patients received a questionnaire, composed of the Olerud-Molander Ankle Score (OMAS), the American Orthopaedic Foot and Ankle Society ankle-hindfoot score (AOFAS), the Euroqol-5D (EQ-5D) for quality of life and the Visual Analogue Scale (VAS) for pain sensation. With a mean follow-up of 5.3 years, 229 patients were included. For all aspects of the questionnaire, there was no significant difference between non-operative and operative treatment in outcome of function and pain: the EQ-5D score was respectively 0.8 vs. 0.9 (p = 0.72), mean VAS score 0.8 vs. 1.3 (p = 0.09), OMA score 84 vs. 84 (p = 0.98) and for the AOFAS 93 vs. 90 (p = 0.28). 33% of the patients who had surgery had revision surgery for implant removal because of persistent pain complaints. In 3% of the surgically treated patients, a wound infection required intravenous antibiotic treatment. In the non-operatively treated cohort, one patient developed a deep venous thrombosis in the fractured leg. CONCLUSION: According to results of this study, in adult patients with an isolated distal fibula and medial clear space ≤6 mm, without proven instability these fractures can safely be treated non-operatively, while avoiding risks and costs of surgery and preserving good long-term outcome in terms of pain and function.

The diagnosis and treatment of isolated type B fibular fractures: Results of a nationwide survey.

INTRODUCTION: In isolated Weber B fractures (type B fibular fractures), ruling out instability is critical for safe conservative treatment. In fractures without evident medial injury, additional diagnostics like MRI scan or gravity stress test should be done to differentiate between a stable and unstable fracture. The aim of the current study is to gain more insight in current practice and treatment of type B fractures by Dutch trauma- and orthopaedic surgeons. MATERIALS & METHODS: In December 2017 and January 2018, 559 trauma surgeons were invited by email to join an online survey. This survey consisted of questions regarding diagnostics and treatment of isolated distal fibula fractures. Also, respondents were asked to state their preferred treatment of eight separate cases. RESULTS: In total, 161 surgeons participated, covering 68 different hospitals in the Netherlands. Of them, 32.0% treat more than 30 ankle fractures a year. Based on regular mortise radiographs, 13.6% of the respondents chose surgical treatment in case of a medial clear space (MCS) > 4 mm, 33.8% in case of a MCS > 6 mm and 45.5% in case of a MCS > 4 mm in addition to the MCS ≥ superior clear space + 1 mm. Moreover, 18.2% make use of additional diagnostics (43.9% repeat mortise view after a week, 16.6% weight bearing radiograph, 8.6% gravity stress view, 7.9% exorotation radiograph, 6.5% MRI scan, 0.7% ultrasound, 16.8% other) and 8% establishes their decision not based on the mortise radiograph. Fibular dislocation of ≥ 2 mm was used as an indication for surgical treatment by 69%. Of them, 56% decides to treat surgically in these cases, even with proven medial stability. CONCLUSION: Many surgeons treat type B fibular fractures with a MCS > 4 mm at mortise view surgically, even without proven medial injury. Rarely, additional diagnostics as MRI or gravity stress test are performed in cases with a MCS 4-6 mm. Consequently many stable ankle fractures are treated operatively unnecessarily.

The alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies.

BACKGROUND: Prediction of radiobiological response is a major challenge in radiotherapy. Of several radiobiological models, the linear-quadratic (LQ) model has been best validated by experimental and clinical data. Clinically, the LQ model is mainly used to estimate equivalent radiotherapy schedules (e.g. calculate the equivalent dose in 2 Gy fractions, EQD2), but increasingly also to predict tumour control probability (TCP) and normal tissue complication probability (NTCP) using logistic models. The selection of accurate LQ parameters α, ß and α/ß is pivotal for a reliable estimate of radiation response. The aim of this review is to provide an overview of published values for the LQ parameters of human tumours as a guideline for radiation oncologists and radiation researchers to select appropriate radiobiological parameter values for LQ modelling in clinical radiotherapy. METHODS AND MATERIALS: We performed a systematic literature search and found sixty-four clinical studies reporting α, ß and α/ß for tumours. Tumour site, histology, stage, number of patients, type of LQ model, radiation type, TCP model, clinical endpoint and radiobiological parameter estimates were extracted. Next, we stratified by tumour site and by tumour histology. Study heterogeneity was expressed by the I2 statistic, i.e. the percentage of variance in reported values not explained by chance. RESULTS: A large heterogeneity in LQ parameters was found within and between studies (I2 > 75%). For the same tumour site, differences in histology partially explain differences in the LQ parameters: epithelial tumours have higher α/ß values than adenocarcinomas. For tumour sites with different histologies, such as in oesophageal cancer, the α/ß estimates correlate well with histology. However, many other factors contribute to the study heterogeneity of LQ parameters, e.g. tumour stage, type of LQ model, TCP model and clinical endpoint (i.e. survival, tumour control and biochemical control). CONCLUSIONS: The value of LQ parameters for tumours as published in clinical radiotherapy studies depends on many clinical and methodological factors. Therefore, for clinical use of the LQ model, LQ parameters for tumour should be selected carefully, based on tumour site, histology and the applied LQ model. To account for uncertainties in LQ parameter estimates, exploring a range of values is recommended.

The effect of time interval between radiotherapy and hyperthermia on planned equivalent radiation dose.

PURPOSE: Thermoradiotherapy is an effective treatment for locally advanced cervical cancer. However, the optimal time interval between radiotherapy and hyperthermia, resulting in the highest therapeutic gain, remains unclear. This study aims to evaluate the effect of time interval on the therapeutic gain using biological treatment planning. METHODS: Radiotherapy and hyperthermia treatment plans were created for 15 cervical cancer patients. Biological modeling was used to calculate the equivalent radiation dose, that is, the radiation dose that results in the same biological effect as the thermoradiotherapy treatment, for different time intervals ranging from 0-4 h. Subsequently, the thermal enhancement ratio (TER, i.e. the ratio of the dose for the thermoradiotherapy and the radiotherapy-only plan) was calculated for the gross tumor volume (GTV) and the organs at risk (OARs: bladder, rectum, bowel), for each time interval. Finally, the therapeutic gain factor (TGF, i.e. TERGTV/TEROAR) was calculated for each OAR. RESULTS: The median TERGTV ranged from 1.05 to 1.16 for 4 h and 0 h time interval, respectively. Similarly, for bladder, rectum and bowel, TEROARs ranged from 1-1.03, 1-1.04 and 1-1.03, respectively. Radiosensitization in the OARs was much less than in the GTV, because temperatures were lower, fractionation sensitivity was higher (lower α/ß) and direct cytotoxicity was assumed negligible in normal tissue. TGFs for the three OARs were similar, and were highest (around 1.12) at 0 h time interval. CONCLUSION: This planning study indicates that the largest therapeutic gain for thermoradiotherapy in cervical cancer patients can be obtained when hyperthermia is delivered immediately before or after radiotherapy.

Measurement and analysis of the impact of time-interval, temperature and radiation dose on tumour cell survival and its application in thermoradiotherapy plan evaluation.

PURPOSE: Biological modelling of thermoradiotherapy may further improve patient selection and treatment plan optimisation, but requires a model that describes the biological effect as a function of variables that affect treatment outcome (e.g. temperature, radiation dose). This study aimed to establish such a model and its parameters. Additionally, a clinical example was presented to illustrate the application. METHODS: Cell survival assays were performed at various combinations of radiation dose (0-8 Gy), temperature (37-42 °C), time interval (0-4 h) and treatment sequence (radiotherapy before/after hyperthermia) for two cervical cancer cell lines (SiHa and HeLa). An extended linear-quadratic model was fitted to the data using maximum likelihood estimation. As an example application, a thermoradiotherapy plan (23 × 2 Gy + weekly hyperthermia) was compared with a radiotherapy-only plan (23 × 2 Gy) for a cervical cancer patient. The equivalent uniform radiation dose (EUD) in the tumour, including confidence intervals, was estimated using the SiHa parameters. Additionally, the difference in tumour control probability (TCP) was estimated. RESULTS: Our model described the dependency of cell survival on dose, temperature and time interval well for both SiHa and HeLa data (R2=0.90 and R2=0.91, respectively), making it suitable for biological modelling. In the patient example, the thermoradiotherapy plan showed an increase in EUD of 9.8 Gy that was robust (95% CI: 7.7-14.3 Gy) against propagation of the uncertainty in radiobiological parameters. This corresponded to a 20% (95% CI: 15-29%) increase in TCP. CONCLUSIONS: This study presents a model that describes the cell survival as a function of radiation dose, temperature and time interval, which is essential for biological modelling of thermoradiotherapy treatments.

Enhancing radiosensitisation of BRCA2-proficient and BRCA2-deficient cell lines with hyperthermia and PARP1-i.

Poly(ADP-ribose)polymerase1 (PARP1) is an important enzyme in regulating DNA replication. Inhibition of PARP1 can lead to collapsed DNA forks which subsequently causes genomic instability, making DNA more susceptible in developing fatal DNA double strand breaks. PARP1-induced DNA damage is generally repaired by homologous recombination (HR), in which BRCA2 proteins are essential. Therefore, BRCA2-deficient tumour cells are susceptible to treatment with PARP1-inhibitors (PARP1-i). Recently, BRCA2 was shown to be down-regulated by hyperthermia (HT) temporarily, and this consequently inactivated HR for several hours. In this study, we investigated whether HT exclusively interferes with HR by analysing thermal radiosensitisation of BRCA2-proficient and deficient cells. After elucidating the equitoxicity of PARP1-i on BRCA2-proficient and deficient cells, we studied the cell survival, apoptosis, DNA damage (γ-H2AX foci and comet assay) and cell cycle distribution after different treatments. PARP1-i sensitivity strongly depends on the BRCA2 status. BRCA2-proficient and deficient cells are radiosensitised by HT, indicating that HT does not exclusively act by inhibition of HR. In all cell lines, the addition of HT to radiotherapy and PARP1-i resulted in the lowest cell survival, the highest levels of DNA damage and apoptotic levels compared to duo-modality treatments. Concluding, HT not only inhibits HR, but also has the capability of radiosensitising BRCA2-deficient cells. Thus, in case of BRCA2-mutation carriers, combining HT with PARP1-i may boost the treatment efficacy. This combination therapy would be effective for all patients with PARP1-i regardless of their BRCA status.

Small larvae in large rivers: observations on downstream movement of European grayling Thymallus thymallus during early life stages.

Behaviour of early life stages of the salmonid European grayling Thymallus thymallus was investigated by assessing the timing of larval downstream movement from spawning areas, the depth at which larvae moved and the distribution of juvenile fish during summer in two large connected river systems in Norway. Trapping of larvae moving downstream and electrofishing surveys revealed that T. thymallus larvae emerging from the spawning gravel moved downstream predominantly during the night, despite light levels sufficient for orientation in the high-latitude study area. Larvae moved in the water mostly at the bottom layer close to the substratum, while drifting debris was caught in all layers of the water column. Few young-of-the-year still resided close to the spawning areas in autumn, suggesting large-scale movement (several km). Together, these observations show that there may be a deliberate, active component to downstream movement of T. thymallus during early life stages. This research signifies the importance of longitudinal connectivity for T. thymallus in Nordic large river systems. Human alterations of flow regimes and the construction of reservoirs for hydropower may not only affect the movement of adult fish, but may already interfere with active movement behaviour of fish during early life stages.

3D radiobiological evaluation of combined radiotherapy and hyperthermia treatments.

PURPOSE: Currently, clinical decisions regarding thermoradiotherapy treatments are based on clinical experience. Quantification of the radiosensitising effect of hyperthermia allows comparison of different treatment strategies, and can support clinical decision-making regarding the optimal treatment. The software presented here enables biological evaluation of thermoradiotherapy plans through calculation of equivalent 3D dose distributions. METHODS: Our in-house developed software (X-Term) uses an extended version of the linear-quadratic model to calculate equivalent radiation dose, i.e. the radiation dose yielding the same effect as the thermoradiotherapy treatment. Separate sets of model parameters can be assigned to each delineated structure, allowing tissue specific modelling of hyperthermic radiosensitisation. After calculation, the equivalent radiation dose can be evaluated according to conventional radiotherapy planning criteria. The procedure is illustrated using two realistic examples. First, for a previously irradiated patient, normal tissue dose for a radiotherapy and thermoradiotherapy plan (with equal predicted tumour control) is compared. Second, tumour control probability (TCP) is assessed for two (otherwise identical) thermoradiotherapy schedules with different time intervals between radiotherapy and hyperthermia. RESULTS: The examples demonstrate that our software can be used for individualised treatment decisions (first example) and treatment optimisation (second example) in thermoradiotherapy. In the first example, clinically acceptable doses to the bowel were exceeded for the conventional plan, and a substantial reduction of this excess was predicted for the thermoradiotherapy plan. In the second example, the thermoradiotherapy schedule with long time interval was shown to result in a substantially lower TCP. CONCLUSIONS: Using biological modelling, our software can facilitate the evaluation of thermoradiotherapy plans and support individualised treatment decisions.

Impact of health problems secondary to SCI one and five years after first inpatient rehabilitation.

STUDY DESIGN: This is a multicenter prospective cohort study. OBJECTIVES: The objective of this study was to describe and compare the impact of health problems secondary to spinal cord injury (SCI) on functioning at home and on social activities at 1 and 5 years after discharge from first inpatient rehabilitation. SETTING: The study was conducted in a Dutch community. METHODS: Participants with SCI who use a wheelchair for everyday mobility (N=110) completed a self-report questionnaire as part of a larger cohort study including four items on extra time needed (body care, bladder and bowel regulation, 'organization' and transportation) and impact of 10 health problems on functioning at home and on social activities. The 10 health problems include secondary health conditions (bladder regulation, bowel regulation, decubitus, pain, spasticity, gain in body weight and edema), psychosocial problems (sexuality, having difficulty with being dependent on help from others) and handicap management. RESULTS: Median extra time needed for self-management and transportation was not significantly higher 1 year after discharge (16 (IQR 13.5) h per week) compared with 5 years after discharge (13 (IQR 17) h per week) (P=0.925). Participants reported slightly less impact, comparing the severity sum-score (range 10-50) of the 10 health problems on functioning at home and in social activities, 5 years post discharge (20 and 17, respectively) than 1 year post discharge (21 and 18, respectively; P<0.05). Most frequently mentioned health problems were handicap management, being dependent on help from others, bladder regulation, bowel regulation, pain and sexuality. CONCLUSIONS: The impact of health problems after SCI is considerable and hardly diminishes over time. These results emphasize the need for structured long-term care for people with SCI.

On-the-road driving performance after use of the antihistamines mequitazine and l-mequitazine, alone and with alcohol.

OBJECTIVE: Previous studies demonstrated that mequitazine produces mild sedation after single doses. Its enantiomer, l-mequitazine, has a stronger potency for the H1 receptor. The aim of the current study was to assess the effects of l-mequitazine and mequitazine, alone and with alcohol, on driving. METHODS: Twenty-five healthy volunteers were treated with l-mequitazine 2.5, 5.0 and 10 mg, mequitazine 10 mg and placebo, alone and in combination with alcohol in a double-blind crossover design. Driving performance was assessed using the standardized highway driving test in normal traffic. Its primary measure is the Standard Deviation of the Lateral Position (SDLP). Secondary measures consisted of an auditory word learning test during driving, and subjective measures of driving performance. RESULTS: L-mequitazine 2.5 and 5.0 mg showed no effect on SDLP in the highway driving test, while SDLP significantly increased after l-mequitazine 10 mg (alone +1.59 cm; with alcohol +1.41 cm) and mequitazine 10 mg (with alcohol +1.17 cm). Alcohol significantly impaired all performance measures (SDLP +2.63 cm) but did not interact with the effects of treatment. Subjective measures indicated that participants were aware of the impairing effects of alcohol, but not of l-mequitazine and mequitazine. CONCLUSION: L-mequitazine can be considered safe to drive in dosages of 2.5 and 5.0 mg. L-mequitazine 10 mg led to mild driving impairment. Alcohol impaired all performance measures and added to the effects of l-mequitazine and mequitazine.

A biological modeling based comparison of two strategies for adaptive radiotherapy of urinary bladder cancer.

Background Adaptive radiotherapy is introduced in the management of urinary bladder cancer to account for day-to-day anatomical changes. The purpose of this study was to determine whether an adaptive plan selection strategy using either the first four cone beam computed tomography scans (CBCT-based strategy) for plan creation, or the interpolation of bladder volumes on pretreatment CT scans (CT-based strategy), is better in terms of tumor control probability (TCP) and normal tissue sparing while taking the clinically applied fractionation schedules also into account. Material and methods With the CT-based strategy, a library of five plans was created. Patients received 55 Gy to the bladder tumor and 40 Gy to the non-involved bladder and lymph nodes, in 20 fractions. With the CBCT-based strategy, a library of three plans was created, and patients received 70 Gy to the tumor, 60 Gy to the bladder and 48 Gy to the lymph nodes, in 30-35 fractions. Ten patients were analyzed for each adaptive plan selection strategy. TCP was calculated applying the clinically used fractionation schedules, as well as a rescaling of the dose from 55 to 70 Gy for the CT-based strategy. For rectum and bowel, equivalent doses in 2 Gy fractions (EQD2) were calculated. Results The CBCT-based strategy resulted in a median TCP of 75%, compared to 49% for the CT-based strategy, the latter improving to 72% upon rescaling the dose to 70 Gy. A median rectum V30Gy (EQD2) of 26% [interquartile range (IQR): 8-52%] was found for the CT-based strategy, compared to 58% (IQR: 55-73%) for the CBCT-based strategy. Also the bowel doses were lower with the CT-based strategy. Conclusions Whereas the higher total bladder TCP for the CBCT-based strategy is due to prescription differences, the adaptive strategy based on CT scans results in the lowest rectum and bowel cavity doses.

Biological modelling of the radiation dose escalation effect of regional hyperthermia in cervical cancer.

BACKGROUND: Locoregional hyperthermia combined with radiotherapy significantly improves locoregional control and overall survival for cervical tumors compared to radiotherapy alone. In this study biological modelling is applied to quantify the effect of radiosensitization for three cervical cancer patients to evaluate the improvement in equivalent dose for the combination treatment with radiotherapy and hyperthermia. METHODS: The Linear-Quadratic (LQ) model extended with temperature-dependent LQ-parameters α and ß was used to model radiosensitization by hyperthermia and to calculate the conventional radiation dose that is equivalent in biological effect to the combined radiotherapy and hyperthermia treatment. External beam radiotherapy planning was performed based on a prescription dose of 46Gy in 23 fractions of 2Gy. Hyperthermia treatment using the AMC-4 system was simulated based on the actual optimized system settings used during treatment. RESULTS: The simulated hyperthermia treatments for the 3 patients yielded a T50 of 40.1 °C, 40.5 °C, 41.1 °C and a T90 of 39.2 °C, 39.7 °C, 40.4 °C, respectively. The combined radiotherapy and hyperthermia treatment resulted in a D95 of 52.5Gy, 55.5Gy, 56.9Gy in the GTV, a dose escalation of 7.3-11.9Gy compared to radiotherapy alone (D95 = 45.0-45.5Gy). CONCLUSIONS: This study applied biological modelling to evaluate radiosensitization by hyperthermia as a radiation-dose escalation for cervical cancer patients. This model is very useful to compare the effectiveness of different treatment schedules for combined radiotherapy and hyperthermia treatments and to guide the design of clinical studies on dose escalation using hyperthermia in a multi-modality setting.

Feasibility of an online well-being intervention for people with spinal cord injury: a pilot study.

STUDY DESIGN: Pre-test and post-test designs with 14 participants. Measurements were taken at baseline (T1), immediately after the intervention (T2) and at 3-month follow-up (T3). OBJECTIVES: Psyfit is an online self-help program designed to enhance well-being in persons with depressed mood. We examined the feasibility of Psyfit in people with spinal cord injury (SCI). SETTING: Community, the Netherlands. METHODS: Participants chose two of the six Psyfit modules. The researcher maintained telephone contact with the participants. Feasibility was inferred from the completion rate of the modules and feedback from the participants. Outcome measures were the Mental Health Inventory-5, the Center for Epidemiological Studies Depression scale and the Warwick-Edinburgh Mental Well-Being Scale. RESULTS: Overall, 75% of the first module and 39% of the second module were completed. Seven participants were considered as study completers and were included in the evaluation. They evaluated Psyfit as a useful program and helpful for persons with SCI. Several technical problems were reported that mainly concerned browser compatibility. An increase in mental health and nonsignificant change of well-being were found at the end of the intervention period, but these were not maintained at follow-up. CONCLUSION: Psyfit seems a potentially feasible program. However, adaptation to the SCI population and further study with a controlled design and utilizing a larger sample size are necessary before it can be recommended as part of SCI rehabilitation.