Densification of activated sludge for better settling performances: experimental characterization in batch column and model parameters calibration.

Conventional activated sludge (CAS) and densified sludge obtained using hydro-cyclone selective wasting were compared at a full-scale water resources recovery facility. The densified tested sludge, containing around 30-50% of aerobic granules, showed enhanced settleability with low and stable sludge volume index (SVI) compared to CAS, which suffered recurrent filamentous bulking. Further in-depth batch settling tests were carried out using a 40 cm diameter column fitted with ultrasonic transducers to monitor both sludge blanket height and vertical velocity profiles. Hindered settling and compression parameters were calibrated from the experiment for latter modelling use. Test sludge displayed more than doubled settling velocities compared to CAS, with hindered settling velocities remaining >3 m·h-1 even at high solids concentrations of 6.85 g·L-1. The compression regime was attained at much higher critical concentration for the test sludge. It also displayed enhanced thickening properties, with concentrations obtained after 30 min of settling being 20.9 and 8.5 g·L-1 respectively for test and control sludge. This allows for a substantial reduction of recirculation rates in practice. These results open perspectives in optimizing existing plant operation as well as clarifier design and modelling using densified sludge.

Effects of acute nitric oxide precursor intake on peripheral and central fatigue during knee extensions in healthy men.

NEW FINDINGS: What is the central question of this study? What is the effect of acute NO precursor intake on vascular function, muscle and cerebral oxygenation and peripheral and central neuromuscular fatigue during knee-extension exercise? What is the main finding and its importance? Acute NO precursor ingestion increases the plasma concentrations of NO precursors (nitrate, arginine and citrulline) and enhances post-ischaemic vasodilatation, but has no significant effect on muscle and cerebral oxygenation, peripheral and central mechanisms of neuromuscular fatigue and, consequently, does not improve exercise performance. ABSTRACT: Nitric oxide (NO) plays an important role in matching blood flow to oxygen demand in the brain and contracting muscles during exercise. Previous studies have shown that increasing NO bioavailability can improve muscle function. The aim of this study was to assess the effect of acute NO precursor intake on muscle and cerebral oxygenation and on peripheral and central neuromuscular fatigue during exercise. In four experimental sessions, 15 healthy men performed a thigh ischaemia-reperfusion test followed by submaximal isometric knee extensions (5 s on-4 s off; 45% of maximal voluntary contraction) until task failure. In each session, subjects drank a nitrate-rich beetroot juice containing 520 mg nitrate (N), N and citrulline (6 g; N+C), N and arginine (6 g; N+A) or a placebo (PLA). Prefrontal cortex and quadriceps near-infrared spectroscopy parameters were monitored continuously. Transcranial magnetic stimulation and femoral nerve electrical stimulation were used to assess central and peripheral determinants of fatigue. The post-ischaemic increase in thigh blood total haemoglobin concentration was larger in N (10.1 ± 3.7 mmol) and N+C (10.9 ± 3.3 mmol) compared with PLA (8.2 ± 2.7 mmol; P < 0.05). Nitric oxide precursors had no significant effect on muscle and cerebral oxygenation or on peripheral and central mechanisms of neuromuscular fatigue during exercise. The total number of knee extensions did not differ between sessions (N, 71.9 ± 33.2; N+A, 73.3 ± 39.4; N+C, 74.6 ± 34.0; PLA, 71.8 ± 39.9; P > 0.05). In contrast to the post-ischaemic hyperaemic response, NO bioavailability in healthy subjects might not be the limiting factor for tissue perfusion and oxygenation during submaximal knee extensions to task failure.

Fetal MRI findings in a retrospective cohort of 26 cases of prenatally diagnosed CHARGE syndrome individuals.

"CHARGE syndrome" (CS) is a multifaceted syndrome associated with a poor prognosis. The prenatal diagnosis remains challenging especially as the fetal anomalies that may evoke suspicion of CS are not comprehensively described. OBJECTIVE: This study aims to identify the anomalies in MRI with suspected CHARGE syndrome and to propose a possible standardization in the image-based prenatal diagnosis of CS. METHODS: This was a retrospective study of 26 fetuses who underwent MRI and had a confirmed diagnosis of CS, as proven by histopathological and/or neonatal examinations and/or the presence of the CHD7 gene mutation. RESULTS: The three most frequent MRI anomalies confirmed at histopathological and/or neonatal examinations were arhinencephaly in 100% (26 of 26), dysplasia of the semicircular canals agenesis (SCA) in 100% (24 of 24), and posterior fossa anomalies in 100% (22 of 22). Our study also revealed short petrous bones with a particular triangular shape in 24 of 24 cases of SCA. Other relevant findings included external ear anomalies in 36% (9 of 25), cleft lip and palate (9 of 9), ventriculomegaly (VMG) (6 of 6), short corpus callosum (3 of 3), and ocular asymmetry in 36.6% (4 of 11). CONCLUSION: Our study emphasizes the interest of fetal MRI in the diagnosis of CS with an adapted knowledge of semiology.

Is combining gait retraining or an exercise programme with education better than education alone in treating runners with patellofemoral pain?A randomised clinical trial.

DESIGN: Single-blind randomised clinical trial. OBJECTIVE: To compare the effects of three 8-week rehabilitation programmes on symptoms and functional limitations of runners with patellofemoral pain (PFP). METHODS: Sixty-nine runners with PFP were randomly assigned to one of three intervention groups: (1) education on symptoms management and training modifications (education); (2) exercise programme in addition to education (exercises); (3) gait retraining in addition to education (gait retraining). Symptoms and functional limitations were assessed at baseline (T0), and after 4, 8 and 20 weeks (T4, T8 and T20) using the Knee Outcome Survey of the Activities of Daily Living Scale (KOS-ADLS) and visual analogue scales (VASs) for usual pain, worst pain and pain during running. Lower limb kinematics and kinetics during running, and isometric strength were also evaluated at T0 and T8. The effects of rehabilitation programmes were assessed using two-way analysis of variance. RESULTS: No significant group × time interactions (p<0.447) were found for KOS-ADLS and VASs. All three groups showed similar improvements at T4, T8 and T20 compared with T0 (p<0.05). Only the exercises group increased knee extension strength following rehabilitation (group × time: p<0.001) and only the gait retraining group (group × time: p<0.001) increased step rate (+7.0%) and decreased average vertical loading rate (-25.4%). CONCLUSION: Even though gait retraining and exercises improved their targeted mechanisms, their addition to education did not provide additional benefits on symptoms and functional limitations. Appropriate education on symptoms and management of training loads should be included as a primary component of treatment in runners with PFP. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT02352909).

Assessment of Placental Perfusion in the Preeclampsia L-NAME Rat Model with High-Field Dynamic Contrast-Enhanced MRI.

PURPOSE: To evaluate placental function and perfusion in a rat model of preeclampsia infused with L-nitro-arginine methyl ester (L-NAME) by dynamic contrast-enhanced (DCE) MRI using gadolinium chelates. METHODS: Pregnant female Sprague-Dawley rats were fitted on embryonic day 16 (E16) with subcutaneous osmotic minipumps loaded to deliver, continuously, L-NAME (50 mg/day per rat; case group) or saline solution (control group). DCE MRI was performed on E19 using gadolinium chelates and a 4.7-T MRI apparatus for small animals. Quantitative analysis was performed using an image software program: placental blood flow (perfusion in mL/min/100 mL of placenta) and fractional volume of the maternal vascular placental compartment (ratio between the placental blood volume and the placental volume, Vb in %) were calculated by compartmental analysis. RESULTS: A total of 176 placentas (27 rats) were analyzed by DCE MRI (97 cases and 79 controls). The model was effective, inducing intrauterine growth retardation, as there was a significant difference between the two groups for placental weight (p < 0.01), fetal weight (p = 0.019), and fetal length (p < 0.01). There was no significant difference in placental perfusion between the L-NAME and control groups (140.1 ± 74.1 vs. 148.9 ± 97.4, respectively; p = 0.496). There was a significant difference between the L-NAME and control groups for Vb (53 ± 12.9 vs. 46.7 ± 9%, respectively; p < 0.01). CONCLUSION: In the L-NAME preeclampsia model, placental perfusion is normal and the fractional blood volume is increased, suggesting that preeclampsia is not always expressed as a result of decreased placental perfusion. This highlights the usefulness of MRI for investigating the physiopathology of preeclampsia.

Pilot Study of a Software-Supported Protocol for Second-Trimester Ultrasound Screening.

OBJECTIVES: To evaluate the feasibility and impact of using a software-supported protocol for routine second-trimester ultrasound scanning. METHODS: We conducted a comparative observational study of 2 sets of 25 randomly selected normal routine second-trimester examinations performed by the same expert sonographer before and 1 year after the introduction of a software-supported protocol. The scanning protocol was identical during both periods and conformed to International Society of Ultrasound in Obstetrics and Gynecology guidelines. Two independent expert sonographers reviewed the temporal sequences of fetal anatomic visualization. The examination duration, number of images, time per stored image, and number of recorded anatomic features according to the International Society of Ultrasound in Obstetrics and Gynecology guidelines were compared between the periods. RESULTS: The mean examination duration and the number of images stored ± SD were both significantly higher during the period with the software-supported protocol than during the previous period (18.9 ± 5.3 versus 15.3 ± 2.8 minutes, respectively; P = .005; and 52.0 ± 2.4 versus 35.2 ± 3.4; P < .001). The mean time per image was also shorter with the software-supported protocol (19 ± 7 versus 26 ± 4 seconds; P < .001). Recording of the placental location, amniotic fluid quantification, cavum septi pellucidi, thoracic shape, both kidneys, both arms, and genitalia was significantly more consistent with the software-supported protocol (P < .001; P = .001; P = .022; P = .050; P = .022; P < .001; and P = .048). CONCLUSIONS: This pilot study suggests that a software-supported protocol standardizing image acquisition may improve operator efficiency during second-trimester ultrasound scans.

Concentration-driven models revisited: towards a unified framework to model settling tanks in water resource recovery facilities.

A new perspective on the modelling of settling behaviour in water resource recovery facilities is introduced. The ultimate goal is to describe in a unified way the processes taking place both in primary settling tanks (PSTs) and secondary settling tanks (SSTs) for a more detailed operation and control. First, experimental evidence is provided, pointing out distributed particle properties (such as size, shape, density, porosity, and flocculation state) as an important common source of distributed settling behaviour in different settling unit processes and throughout different settling regimes (discrete, hindered and compression settling). Subsequently, a unified model framework that considers several particle classes is proposed in order to describe distributions in settling behaviour as well as the effect of variations in particle properties on the settling process. The result is a set of partial differential equations (PDEs) that are valid from dilute concentrations, where they correspond to discrete settling, to concentrated suspensions, where they correspond to compression settling. Consequently, these PDEs model both PSTs and SSTs.

Angiogenic activity of breast cancer patients' monocytes reverted by combined use of systems modeling and experimental approaches.

Angiogenesis plays a key role in tumor growth and cancer progression. TIE-2-expressing monocytes (TEM) have been reported to critically account for tumor vascularization and growth in mouse tumor experimental models, but the molecular basis of their pro-angiogenic activity are largely unknown. Moreover, differences in the pro-angiogenic activity between blood circulating and tumor infiltrated TEM in human patients has not been established to date, hindering the identification of specific targets for therapeutic intervention. In this work, we investigated these differences and the phenotypic reversal of breast tumor pro-angiogenic TEM to a weak pro-angiogenic phenotype by combining Boolean modelling and experimental approaches. Firstly, we show that in breast cancer patients the pro-angiogenic activity of TEM increased drastically from blood to tumor, suggesting that the tumor microenvironment shapes the highly pro-angiogenic phenotype of TEM. Secondly, we predicted in silico all minimal perturbations transitioning the highly pro-angiogenic phenotype of tumor TEM to the weak pro-angiogenic phenotype of blood TEM and vice versa. In silico predicted perturbations were validated experimentally using patient TEM. In addition, gene expression profiling of TEM transitioned to a weak pro-angiogenic phenotype confirmed that TEM are plastic cells and can be reverted to immunological potent monocytes. Finally, the relapse-free survival analysis showed a statistically significant difference between patients with tumors with high and low expression values for genes encoding transitioning proteins detected in silico and validated on patient TEM. In conclusion, the inferred TEM regulatory network accurately captured experimental TEM behavior and highlighted crosstalk between specific angiogenic and inflammatory signaling pathways of outstanding importance to control their pro-angiogenic activity. Results showed the successful in vitro reversion of such an activity by perturbation of in silico predicted target genes in tumor derived TEM, and indicated that targeting tumor TEM plasticity may constitute a novel valid therapeutic strategy in breast cancer.

Impact of seawater acidification on pH at the tissue-skeleton interface and calcification in reef corals.

Insight into the response of reef corals and other major marine calcifiers to ocean acidification is limited by a lack of knowledge about how seawater pH and carbonate chemistry impact the physiological processes that drive biomineralization. Ocean acidification is proposed to reduce calcification rates in corals by causing declines in internal pH at the calcifying tissue-skeleton interface where biomineralization takes place. Here, we performed an in vivo study on how partial-pressure CO(2)-driven seawater acidification impacts intracellular pH in coral calcifying cells and extracellular pH in the fluid at the tissue-skeleton interface [subcalicoblastic medium (SCM)] in the coral Stylophora pistillata. We also measured calcification in corals grown under the same conditions of seawater acidification by measuring lateral growth of colonies and growth of aragonite crystals under the calcifying tissue. Our findings confirm that seawater acidification decreases pH of the SCM, but this decrease is gradual relative to the surrounding seawater, leading to an increasing pH gradient between the SCM and seawater. Reductions in calcification rate, both at the level of crystals and whole colonies, were only observed in our lowest pH treatment when pH was significantly depressed in the calcifying cells in addition to the SCM. Overall, our findings suggest that reef corals may mitigate the effects of seawater acidification by regulating pH in the SCM, but they also highlight the role of calcifying cell pH homeostasis in determining the response of reef corals to changes in external seawater pH and carbonate chemistry.

Good modelling practice in applying computational fluid dynamics for WWTP modelling.

Computational fluid dynamics (CFD) modelling in the wastewater treatment (WWT) field is continuing to grow and be used to solve increasingly complex problems. However, the future of CFD models and their value to the wastewater field are a function of their proper application and knowledge of their limits. As has been established for other types of wastewater modelling (i.e. biokinetic models), it is timely to define a good modelling practice (GMP) for wastewater CFD applications. An International Water Association (IWA) working group has been formed to investigate a variety of issues and challenges related to CFD modelling in water and WWT. This paper summarizes the recommendations for GMP of the IWA working group on CFD. The paper provides an overview of GMP and, though it is written for the wastewater application, is based on general CFD procedures. A forthcoming companion paper to provide specific details on modelling of individual wastewater components forms the next step of the working group.

NHS-IL2 combined with radiotherapy: preclinical rationale and phase Ib trial results in metastatic non-small cell lung cancer following first-line chemotherapy.

BACKGROUND: NHS-IL2 (selectikine, EMD 521873, MSB0010445) consists of human NHS76 (antibody specific for necrotic DNA) fused to genetically modified human interleukin 2 (IL-2) and selectively activates the high-affinity IL-2 receptor. Based on an evolving investigational concept to prime the tumor microenvironment with ionizing radiation prior to initiating immunotherapy, 2 related studies were conducted and are reported here. The first, a preclinical study, tests the systemic effect of the immunocytokine NHS-IL2 and radiotherapy in a lung carcinoma animal model; the second, a phase Ib trial in patients with metastatic non-small cell lung carcinoma (NSCLC), was designed to determine the safety and tolerability of NHS-IL2 in combination with radiotherapy directly following first-line palliative chemotherapy. METHODS: Tumor-bearing C57Bl/6 mice were treated with NHS-IL2 alone (5 mg/kg; days 7-9), fractionated radiotherapy (3.6 Gy; days 0-4) plus cisplatin (4 mg/kg; day 0), or the triple combination. Metastatic NSCLC patients who achieved disease control with first-line palliative chemotherapy were enrolled in the phase Ib trial. Patients received local irradiation (5x 4 Gy) of a single pulmonary nodule. Dose-escalated NHS-IL2 was administered as 1-h intravenous infusion on 3 consecutive days every 3 weeks. RESULTS: NHS-IL2 plus radiotherapy induced immune response activation and complete tumor growth regressions in 80%-100% of mice. In patients with metastatic NSCLC treated with NHS-IL2 (3, 3, and 7 patients in the 0.15-mg/kg, 0.30-mg/kg, and 0.45-mg/kg cohorts, respectively), maximum tolerated dose was not reached. Most frequently reported adverse events were fatigue, anorexia, and rash. Transient increases in leukocyte subsets were observed. In 3 patients, thyroid gland dysfunction occurred. No objective responses were reported; long-term survival was observed in 2 patients, including 1 patient with long-term tumor control. CONCLUSIONS: Combining NHS-IL2 with radiotherapy achieved synergistic antitumor activity in preclinical studies, supporting the use in lung cancer patients. This combination was well tolerated and 2 of 13 patients achieved long-term survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT00879866.

MART-1 peptide vaccination plus IMP321 (LAG-3Ig fusion protein) in patients receiving autologous PBMCs after lymphodepletion: results of a Phase I trial.

BACKGROUND: Immunotherapy offers a promising novel approach for the treatment of cancer and both adoptive T-cell transfer and immune modulation lead to regression of advanced melanoma. However, the potential synergy between these two strategies remains unclear. METHODS: We investigated in 12 patients with advanced stage IV melanoma the effect of multiple MART-1 analog peptide vaccinations with (n = 6) or without (n = 6) IMP321 (LAG-3Ig fusion protein) as an adjuvant in combination with lymphodepleting chemotherapy and adoptive transfer of autologous PBMCs at day (D) 0 (Trial registration No: NCT00324623). All patients were selected on the basis of ex vivo detectable MART-1-specific CD8 T-cell responses and immunized at D0, 8, 15, 22, 28, 52, and 74 post-reinfusion. RESULTS: After immunization, a significant expansion of MART-1-specific CD8 T cells was measured in 83% (n = 5/6) and 17% (n = 1/6) of patients from the IMP321 and control groups, respectively (P < 0.02). Compared to the control group, the mean fold increase of MART-1-specific CD8 T cells in the IMP321 group was respectively >2-, >4- and >6-fold higher at D15, D30 and D60 (P < 0.02). Long-lasting MART-1-specific CD8 T-cell responses were significantly associated with IMP321 (P < 0.02). At the peak of the response, MART-1-specific CD8 T cells contained higher proportions of effector (CCR7⁻ CD45RA⁺/⁻) cells in the IMP321 group (P < 0.02) and showed no sign of exhaustion (i.e. were mostly PD1⁻CD160⁻TIM3⁻LAG3⁻2B4⁺/⁻). Moreover, IMP321 was associated with a significantly reduced expansion of regulatory T cells (P < 0.04); consistently, we observed a negative correlation between the relative expansion of MART-1-specific CD8 T cells and of regulatory T cells. Finally, although there were no confirmed responses as per RECIST criteria, a transient, 30-day partial response was observed in a patient from the IMP321 group. CONCLUSIONS: Vaccination with IMP321 as an adjuvant in combination with lymphodepleting chemotherapy and adoptive transfer of autologous PBMCs induced more robust and durable cellular antitumor immune responses, supporting further development of IMP321 as an adjuvant for future immunotherapeutic strategies.

T-cell activation by treatment of cancer patients with EMD 521873 (Selectikine), an IL-2/anti-DNA fusion protein.

BACKGROUND: EMD 521873 (Selectikine or NHS-IL2LT) is a fusion protein consisting of modified human IL-2 which binds specifically to the high-affinity IL-2 receptor, and an antibody specific for both single- and double-stranded DNA, designed to facilitate the enrichment of IL-2 in tumor tissue. METHODS: An extensive analysis of pharmacodynamic (PD) markers associated with target modulation was assessed during a first-in-human phase I dose-escalation trial of Selectikine. RESULTS: Thirty-nine patients with metastatic or locally advanced tumors refractory to standard treatments were treated with increasing doses of Selectikine, and nine further patients received additional cyclophosphamide. PD analysis, assessed during the first two treatment cycles, revealed strong activation of both CD4+ and CD8+ T-cells and only weak NK cell activation. No dose response was observed. As expected, Treg cells responded actively to Selectikine but remained at lower frequency than effector CD4+ T-cells. Interestingly, patient survival correlated positively with both high lymphocyte counts and low levels of activated CD8+ T-cells at baseline, the latter of which was associated with enhanced T-cell responses to the treatment. CONCLUSIONS: The results confirm the selectivity of Selectikine with predominant T-cell and low NK cell activation, supporting follow-up studies assessing the clinical efficacy of Selectikine for cancer patients.

The influence of photosynthesis on host intracellular pH in scleractinian corals.

The regulation of intracellular pH (pHi) is a fundamental aspect of cell physiology that has received little attention in studies of reef-building corals and symbiotic cnidarians. Here, we investigated the hypothesis that dynamic changes in the pHi of coral host cells are controlled by the photosynthetic activity of the coral's dinoflagellate symbionts. Using live cell imaging and the pH-sensitive dye SNARF-1, we tracked pH in symbiont-containing and symbiont-free cells isolated from the reef coral Stylophora pistillata. We characterised the response of coral pHi in the presence of a photosynthetic inhibitor, the dynamics of coral pHi during light exposure and how pHi values vary on exposure to a range of irradiance levels lying within the coral's photosynthesis-irradiance response curve. Our results demonstrate that increases in coral pHi are dependent on photosynthetic activity of intracellular symbionts and that pHi recovers under darkness to values that match those of symbiont-free cells. Furthermore, we show that the timing of the pHi response is governed by irradiance level and that pHi increases to irradiance-specific steady-state values. Minimum steady-state pHi values of 7.05 ± 0.05 were obtained under darkness and maximum values of 7.46 ± 0.07 were obtained under saturating irradiance. As changes in pHi often affect organism homeostasis, there is a need for continued research into acid/base regulation in symbiotic corals. More generally, these results represent the first characterization of photosynthesis-driven pHi changes in animal cells.

Distribution and degradation trend of micropollutants in a surface flow treatment wetland revealed by 3D numerical modelling combined with LC-MS/MS.

Conventional wastewater treatment plants are not designed to treat micropollutants; thus, for 20 years, several complementary treatment systems, such as surface flow wetlands have been used to address this issue. Previous studies demonstrate that higher residence time and low global velocities promote nutrient removal rates or micropollutant photodegradation. Nevertheless, these studies were restricted to the system limits (inlet/outlet). Therefore, detailed knowledge of water flow is crucial for identifying areas that promote degradation and optimise surface flow wetlands. The present study combines 3D water flow numerical modelling and liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS/MS). Using this numerical model, validated by tracer experimental data, several velocity areas were distinguished in the wetland. Four areas were selected to investigate the waterflow influence and led to the following results: on the one hand, the number and concentration of micropollutants are independent of the waterflow, which could be due to several assumptions, such as the chronic exposure associated with a low Reynolds number; on the other hand, the potential degradation products (metabolites) were also assessed in the sludge to investigate the micropollutant biodegradation processes occurring in the wetland; micropollutant metabolites or degradation products were detected in higher proportions (both number and concentration) in lower flow rate areas. The relation to higher levels of plant and microorganism metabolites suggests higher biological activity that promotes degradation.

MRI based morphological examination of the placenta.

Ultrasound is widely used as the initial diagnostic imaging modality during pregnancy with both high spatial and temporal resolution. Although MRI in pregnancy has long focused on the fetus, its use in placental imaging has greatly increased over recent years. In addition to the possibilities of evaluating function, MRI with a wide field of view and high contrast resolution allows characterization of placental anatomy, particularly in situations that are difficult to specify with ultrasound, especially for suspected placenta accreta. MRI also appears to be a particularly useful examination for the anatomical evaluation of the placenta independent of maternal body habitus or fetal position. Indeed, surprisingly little attention is paid to the placenta in MRI when the indication for the examination is fetal. Thus, some aspects of the placenta seem to us to be important to be recognized by the radiologist and to be described on the MRI report. In this review, we will describe MRI sequences used for, and common features seen in, imaging of i) the normal placenta, ii) abnormal aspects of the placenta that should be identified on MRI performed for fetal reason, and iii) placental anomalies for which placental MRI may be indicated.

Kinesiotaping for the Rehabilitation of Rotator Cuff-Related Shoulder Pain: A Randomized Clinical Trial.

BACKGROUND: Kinesiotaping (KT) has been widely used in clinical practice. Current evidence is insufficient to support the use of KT for treating rotator cuff-related shoulder pain (RCRSP), as its mid- and long-term effects have not been investigated. HYPOTHESES: Individuals using KT will achieve faster improvements in symptoms and functional limitations compared with those not using it. They will also present a greater increase in pain-free range of motion (ROM) and acromiohumeral distance (AHD) at the end of the treatment. STUDY DESIGN: Randomized controlled trial (NCT02881021). LEVEL OF EVIDENCE: Therapy, level 1b. METHODS: A total of 52 individuals with RCRSP, randomly assigned to 1 of 2 groups (experimental: KT; control: no-KT), underwent a 6-week rehabilitation program composed of 10 physical therapy sessions. KT was added to the treatment of the KT group. Symptoms and functional limitations were assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire (primary outcome); Brief Pain Inventory (BPI); and Western Ontario Rotator Cuff (WORC) index at baseline, 3 weeks, 6 weeks, 12 weeks, and 6 months. AHD, pain-free ROM, and full ROM were measured at baseline and at week 6. The effects of KT were assessed using a nonparametric analysis for longitudinal data. RESULTS: No significant group × time interactions (0.112 ≤ P ≤ 0.726) were found for all outcomes. Time effects were observed as both groups showed significant improvements for all studied outcomes (DASH, BPI, and WORC, p < 0.0001; AHD, p = 0.017; pain-free ROM, p < 0.0001; and full ROM abduction, p ≤ 0.0001). CONCLUSION: Whereas symptoms, functional limitations, ROM, and AHD improved in both groups, the addition of KT did not lead to superior outcomes compared with exercise-based treatment alone, in the mid and long term, for individuals with RCRSP. CLINICAL RELEVANCE: Clinicians should not expect supplementary mid- or long-term gains with KT to reduce pain, improve shoulder function and ROM, or increase AHD if a rehabilitation program focusing on shoulder neuromuscular control is concurrently provided as treatment for individuals with RCRSP.

Human placental perfusion measured using dynamic contrast enhancement MRI.

OBJECTIVES: To evaluate the feasibility of dynamic contrast enhanced magnetic resonance imaging (DCE MRI) and measure values of in vivo placental perfusion in women. METHODS: This study was part of the Placentimage trial (NCT01092949). Gadolinium-chelate (Gd) enhanced dynamic MRI was performed two days before termination of pregnancies at 16 to 34 weeks gestational age (GA). Quantitative analysis was performed using one-compartment intravascular modeling. DCE perfusion parameters were analyzed across GA and were compared in IUGR and AGA fetuses. RESULTS: 134 patients were enrolled. After quality control check, 62 DCE MRI were analyzed including 48 and 14 pregnancies with normal and abnormal karyotypes, respectively. Mean placental blood flow was 129±61 mL/min/100ml in cases with normal karyotypes. Fetuses affected by IUGR (n = 13) showed significantly lower total placental blood flow values than AGA fetuses (n = 35) (F total = 122±88 mL/min versus 259±34 mL/min, p = 0.002). DCE perfusion parameters showed a linear correlation with GA. CONCLUSIONS: Measuring placental perfusion in vivo is possible using DCE MRI. Although this study has many limitations it gives us the first DCE MRI values that provide a potential standard for future research into placental perfusion methods and suggests that placental functional parameters are altered in IUGR pregnancies.