Author Correction: Mapping the world's free-flowing rivers.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Mapping the world's free-flowing rivers.

Free-flowing rivers (FFRs) support diverse, complex and dynamic ecosystems globally, providing important societal and economic services. Infrastructure development threatens the ecosystem processes, biodiversity and services that these rivers support. Here we assess the connectivity status of 12 million kilometres of rivers globally and identify those that remain free-flowing in their entire length. Only 37 per cent of rivers longer than 1,000 kilometres remain free-flowing over their entire length and 23 per cent flow uninterrupted to the ocean. Very long FFRs are largely restricted to remote regions of the Arctic and of the Amazon and Congo basins. In densely populated areas only few very long rivers remain free-flowing, such as the Irrawaddy and Salween. Dams and reservoirs and their up- and downstream propagation of fragmentation and flow regulation are the leading contributors to the loss of river connectivity. By applying a new method to quantify riverine connectivity and map FFRs, we provide a foundation for concerted global and national strategies to maintain or restore them.

Strategic basin and delta planning increases the resilience of the Mekong Delta under future uncertainty.

The climate resilience of river deltas is threatened by rising sea levels, accelerated land subsidence, and reduced sediment supply from contributing river basins. Yet, these uncertain and rapidly changing threats are rarely considered in conjunction. Here we provide an integrated assessment, on basin and delta scales, to identify key planning levers for increasing the climate resilience of the Mekong Delta. We find, first, that 23 to 90% of this unusually productive delta might fall below sea level by 2100, with the large uncertainty driven mainly by future management of groundwater pumping and associated land subsidence. Second, maintaining sediment supply from the basin is crucial under all scenarios for maintaining delta land and enhancing the climate resilience of the system. We then use a bottom-up approach to identify basin development scenarios that are compatible with maintaining sediment supply at current levels. This analysis highlights, third, that strategic placement of hydropower dams will be more important for maintaining sediment supply than either projected increases in sediment yields or improved sediment management at individual dams. Our results demonstrate 1) the need for integrated planning across basin and delta scales, 2) the role of river sediment management as a nature-based solution to increase delta resilience, and 3) global benefits from strategic basin management to maintain resilient deltas, especially under uncertain and changing conditions.

CT-like images based on T1-weighted gradient echo MRI sequences for the assessment of fractures of the hand and wrist compared to CT.

OBJECTIVE: To evaluate the performance of a 3D T1-weighted gradient-echo (3D T1GRE) computed tomography (CT)-like magnetic resonance imaging (MRI) sequence for detecting and assessing wrist and hand fractures compared to conventional CT. METHODS: Subjects with acute wrist or hand fracture in CT underwent additional 3 T MRI including a CT-like 3D T1GRE sequence and were compared to patients without fractures. Two radiologists assessed fracture morphology on both modalities according to the Arbeitsgemeinschaft Osteosynthese (AO) and graded image quality and diagnostic confidence on a 5-point Likert scale. Besides diagnostic test evaluation, differences in image quality and diagnostic confidence between CT-like MRI and CT were calculated using the Wilcoxon test. Agreement of AO classification between modalities and readers was assessed using Cohen's Kappa. RESULTS: Twenty-eight patients with 43 fractures and 43 controls were included. Image quality (3D T1GRE 1.19 ± 0.37 vs. CT 1.22 ± 0.42; p = 0.65) and diagnostic confidence (3D T1GRE 1.28 ± 0.53 vs. CT 1.28 ± 0.55; p = 1.00) were rated excellent for both modalities. Regarding the AO classification, intra- (rater 1 and rater 2, κ = 0.89; 95% CI 0.80-0.97) and interrater agreement were excellent (3D T1GRE, κ = 0.82; 95% CI, 0.70-0.93; CT, κ = 0.85; 95% CI, 0.75-0.94). CT-like MRI showed excellent sensitivity, specificity and accuracy for fracture detection (reader 1: 1.00, 0.92, 0.96; reader 2: 0.98, 0.94, 0.96). CONCLUSION: CT-like MRI is a comparable alternative to CT for assessing hand and wrist fractures, offering the advantage of avoiding radiation exposure.

Effects of a single transdermal administration of flunixin meglumine in early postpartum Holstein Friesian dairy cows: Part 1. Inflammatory and metabolic markers, uterine health, and indicators of pain.

The objectives of this study were to assess the effects of a single transdermal administration of flunixin meglumine (FM) in early postpartum Holstein Friesian dairy cows on serum concentrations of inflammatory and metabolic markers, uterine health, and indicators of pain. The hypothesis was that the anti-inflammatory, antipyretic, and analgetic effects of the pharmaceutic agent would reduce systemic inflammation, resulting in improved metabolic and inflammatory profile, diminished incidence of metritis, and reduced expression of pain. A total of 500 cows (153 primiparous, 347 multiparous) from 3 different commercial dairy farms in the northeast of Germany were included in a randomized controlled clinical trial. Farms were preselected based on high haptoglobin concentrations in their fresh lactating cows. Cows were excluded if they had experienced dystocia, stillbirth, or twin birth, or if they showed any signs of milk fever, retained fetal membranes, or fever (>40°C). The cows were treated once with either FM (3.33 mg/kg) or a placebo as control (CON) through transdermal administration between 24 to 36 h postpartum (d 2). General health examinations were performed (daily from d 2-8 and additionally on d 15 postpartum), vaginal discharge was assessed using the Metricheck device (d 8 and 15 postpartum) and serum samples were analyzed for inflammatory and metabolic markers (d 2, 4, and 6 postpartum). Effects of treatment, parity, sampling day, and their interactions were evaluated using mixed effects models. Primiparous cows treated with FM showed lower serum haptoglobin concentrations (0.90 ± 0.08 vs. 1.17 ± 0.07 g/L; ± standard error of the mean) and higher serum albumin concentrations (35.5 ± 0.31 vs. 34.8 ± 0.31 g/L) on d 6 postpartum. They also had a lower risk for purulent vaginal discharge with or without a fever compared with CON cows on d 15 postpartum (odds ratio for CON vs. FM: 1.63, 95% CI: 1.26-2.00), and body temperature was lower throughout the first 15 d in milk (39.1 ± 0.11 vs. 39.2 ± 0.11°C). Multiparous cows treated with FM had lower serum ß-hydroxybutyrate concentrations on d 4 postpartum (0.71 ± 0.05 vs. 0.78 ± 0.05 mmol/L) and d 6 postpartum (0.74 ± 0.05 vs. 0.80 ± 0.05 mmol/L). Regardless of parity, FM-treated cows were significantly less likely to abduct their tail from their body (14.3 vs. 23.6%) and show an arched back (27.9 vs. 39.7%) on the day after treatment compared with CON cows. It can be concluded that FM treatment slightly reduced inflammation and diminished the risk for metritis in primiparous cows, improved metabolic profile in multiparous cows, and reduced expressions of pain in all cows.

Effects of a single transdermal administration of flunixin meglumine in early postpartum Holstein Friesian dairy cows: Part 2. Milk yield, culling risk, and reproductive performance.

This study was conducted to assess the effects of a single transdermal administration of flunixin meglumine (FM) in early postpartum Holstein Friesian dairy cows on milk yield, culling risk, and reproductive performance. We hypothesized that FM treatment would reduce systemic inflammation, leading to higher milk yield, reduced culling risk, and better reproductive performance in the subsequent lactation. Holstein Friesian dairy cows [n = 500, 153 primiparous (PRIM), 347 multiparous (MULT)] from 3 farms in northeast Germany were enrolled in a prospective, randomized controlled clinical trial. Farms at risk for cows with excessive postpartum inflammation were identified in a preliminary trial by measuring serum haptoglobin concentrations in their fresh lactating cows. Only cows that had a eutocic birth and delivered a singleton calf alive, with no signs of milk fever or retained fetal membranes and rectal temperature ≤40°C at first clinical examination, were included within 24 to 36 h postpartum. Treatment included a single transdermal administration of either FM (3.33 mg/kg) or a placebo as control (CON). Milk production, milk solids, urea, and somatic cell count were recorded monthly for 8 mo after calving. Culling risk, first-service conception risk, and days open were retrieved from the farms' herd management software. Separate models for PRIM and MULT cows were built for most parameters because of significant effects of parity and parity × treatment interaction. Energy-corrected milk yield from 8 monthly Dairy Herd Improvement-equivalent tests was slightly greater in PRIM cows treated with FM (29.51 and 30.73 ± 1.35 kg, CON vs. FM), whereas it was reduced in treated MULT cows (38.23 and 37.47 ± 1.17 kg, CON vs. FM) compared with CON. Milk fat and protein yields were greater in FM-treated PRIM cows and lower in treated MULT cows compared with CON. Milk urea and somatic cell count were not affected by treatment. No differences in culling risk, first-service conception risk, or days open were observed. We conclude that a single transdermal administration of FM in early postpartum dairy cows on farms at risk for excessive postpartum inflammation slightly increased milk, milk fat, and milk protein yields in PRIM cows and decreased these variables in MULT cows. Neither culling risk nor fertility was affected by treatment in this study.

[The ulnocarpal complex : New clinical and radiological considerations]. / Der ulnokarpale Komplex : Neue klinische und radiologische Überlegungen.

CLINICAL ISSUE: The triangular fibrocartilage complex (TFCC) is an anatomically complex structure with high demands on spatial and contrast resolution in imaging. RADIOLOGICAL METHODS: The central, predominantly avascular articular disc can be distinguished from the ligamentous, vascularized periphery. Imaging methods include magnetic resonance imaging (MRI, preferably contrast-enhanced) as well as MR and computed tomography (CT) arthrography. DIAGNOSTIC INNOVATIONS: While high-resolution MRI represents the standard diagnostic tool for the TFCC in general, arthrographic imaging is particularly useful for assessment of the foveal (proximal) lamina of the TFCC. In radiological reporting, the convergence of the TFCC periphery towards the ulnar styloid process and the ulnar fovea must be considered. ACHIEVEMENTS: The Palmer classification is suitable for evaluating lesions of the articular disc, whereas the Atzei classification is superior for lesions of the ulnar TFCC insertions. PRACTICAL RECOMMENDATION: Use of a high-resolution examination technique and anatomy-based image interpretation are important for reliable MRI of the TFCC.

Kidney injury enhances renal G-CSF expression and modulates granulopoiesis and human neutrophil CD177 in vivo.

Kidney injury significantly increases overall mortality. Neutrophilic granulocytes (neutrophils) are the most abundant human blood leukocytes. They are characterized by a high turnover rate, chiefly controlled by granulocyte colony stimulating factor (G-CSF). The role of kidney injury and uremia in regulation of granulopoiesis has not been reported. Kidney transplantation, which inherently causes ischemia-reperfusion injury of the graft, elevated human neutrophil expression of the surface glycoprotein CD177. CD177 is among the most G-CSF-responsive neutrophil genes and reversibly increased on neutrophils of healthy donors who received recombinant G-CSF. In kidney graft recipients, a transient rise in neutrophil CD177 correlated with renal tubular epithelial G-CSF expression. In contrast, CD177 was unaltered in patients with chronic renal impairment and independent of renal replacement therapy. Under controlled conditions of experimental ischemia-reperfusion and unilateral ureteral obstruction injuries in mice, renal G-CSF mRNA and protein expression significantly increased and systemic neutrophilia developed. Human renal tubular epithelial cell G-CSF expression was promoted by hypoxia and proinflammatory cytokine interleukin 17A in vitro. Clinically, recipients of ABO blood group-incompatible kidney grafts developed a larger rise in neutrophil CD177. Their grafts are characterized by complement C4d deposition on the renal endothelium, even in the absence of rejection. Indeed, complement activation, but not hypoxia, induced primary human endothelial cell G-CSF expression. Our data demonstrate that kidney injury induces renal G-CSF expression and modulates granulopoiesis. They delineate differential G-CSF regulation in renal epithelium and endothelium. Altered granulopoiesis may contribute to the systemic impact of kidney injury.

[Special aspects of fractures of the distal forearm]. / Spezielle Aspekte der Frakturen am distalen Unterarm.

BACKGROUND: Fractures of the distal forearm, especially fractures of the distal radius which are the most common fracture in humans, are of increasing socioeconomic relevance due to the increasing incidence and the increasing costs that are associated with the popularity of palmar plating. OBJECTIVES: Radiological imaging for diagnosis and follow-up are presented with special focus on new biomechanical fracture concepts such as the four-corner concept. MATERIALS AND METHODS: The basic literature and expert opinions are evaluated and discussed. RESULTS: In intra-articular fractures of the distal radius, plain radiographs must be supplemented by computed tomography (CT). Direct CT arthrography allows not only analysis of the fracture pattern, but also detection of accompanying injuries of the carpus, especially the scapholunate ligament, and the ulnocarpal complex. The plain radiographs should also be analyzed for accompanying injuries. Therefore, both acquisition of the imaging data and their morphometrical analysis have to be standardized. CONCLUSIONS: In addition to diagnosis and follow-up, radiological imaging plays a decisive role in the treatment of distal forearm fractures. CT and direct CT arthrography have become important tools in intra-articular distal radius fractures.

Automation in cell and gene therapy manufacturing: from past to future.

As more and more cell and gene therapies are being developed and with the increasing number of regulatory approvals being obtained, there is an emerging and pressing need for industrial translation. Process efficiency, associated cost drivers and regulatory requirements are issues that need to be addressed before industrialisation of cell and gene therapies can be established. Automation has the potential to address these issues and pave the way towards commercialisation and mass production as it has been the case for 'classical' production industries. This review provides an insight into how automation can help address the manufacturing issues arising from the development of large-scale manufacturing processes for modern cell and gene therapy. The existing automated technologies with applicability in cell and gene therapy manufacturing are summarized and evaluated here.

Influence of patient-specific anatomy on medical computed tomography and risk evaluation of minimally invasive surgery at the otobasis.

PURPOSE: With the increasing use of new minimally invasive approaches in temporal bone surgery, the need arises for evaluation of the risk of injury to sensitive anatomical structures. The factors that influence the measurement uncertainty (variation in representation of position and shape of anatomical structures) of imaging are of relevance. We investigate the effect of patients' anatomy on the measurement uncertainty of medical CT. METHODS: Six formalin-fixed temporal bones were used, fiducial markers were bone-implanted, and 20 CT scans of each temporal bone were generated. Surgically threatened anatomical structures of importance were defined. Manual segmentation was performed to create 3D surface models, and different Gaussian filters were applied. Analysis points were established along the border of the superior semicircular canal to determine the deviation between the 3D images of the labyrinth. The standard uncertainty was calculated, and one-way analysis of variance was performed (significance level = 5%) to evaluate the effect of certain factors (patient, side, Gaussian filter) on the measurement uncertainty. RESULTS: The influence of patient-specific anatomy on the measurement uncertainty of medical CT (p = 0.049) was demonstrated for the first time. The applied Gaussian filter (p = 0.622) and the patient's side (p = 0.341) showed no significant effect. CONCLUSION: The applied method and the results of the statistical analysis suggest that the patient's individual anatomical conditions affect the measurement uncertainty of medical CT. Thus, the patient's anatomy must be considered as an important influencing factor during risk evaluation concerning minimally invasive and image-guided surgery.

[Distal radius fractures : Update on imaging]. / Distale Radiusfrakturen : Update zur Bildgebung.

Distal radius fractures are associated with high individual and socioeconomic relevance. Optimized radiography and computed tomography (CT) imaging are essential for individualized therapy planning. Plain CT imaging with 3D reconstruction and digital removal of the carpus and ulna is helpful for choosing the surgical approach in the presence of intra-articular radius fractures. If the fracture line leads towards the scapholunate compartment, ligamentous injury requiring treatment can be detected or ruled out before surgery with the help of direct CT arthrography (CTA). Acquisition of imaging data and morphometrical analysis must be standardized and reproducible. In the diagnostics of distal radius fractures it is necessary for radiologists and surgeons to use a unified fracture classification.

[Radiology of the distal radioulnar joint and the ulnocarpal complex]. / Radiologie des distalen Radioulnargelenks und des ulnokarpalen Komplexes.

X-ray images exposed in neutral position and radiocarpally centred are essential in imaging of the distal radioulnar joint (DRUJ). The anatomic orientation of the DRUJ is favourable for acquiring transaxial scans to display its anatomy, subtle derangements, osteoarthritis and intra-articular fractures free from superpositions. The triangular fibrocartilage complex (TFCC) is the most important stabilizer of the DRUJ. Provided that a focused clinical indication is given, high-resolution images are acquired, and an intra-venous or intra-articular contrast-agent is applied, all TFCC structures and destabilizing lesions can be displayed with the use of CT and MRI.

[Ligament injuries of fingers and thumbs]. / Bandverletzungen am Daumen und an den Fingern.

Degenerative and traumatic ligament lesions of the carpometacarpal joints frequently occur at the thumb ray, whereas the carpometacarpal amphiarthrosis of other finger rays are rarely affected. The metacarpophalangeal and interphalangeal joints of the thumb and fingers are stabilized by bilaterally running collateral ligaments and palmar plates. At the base of the metacarpophalangeal joints, several ligaments of the extensor hoods guide the extensor tendons and coordinate the fine motoric skills of phalangeal flexing and extending. Several annular and cruciform ligaments hold the flexor tendons close to the finger skeleton. Other than at the wrist, differentiation between dynamic and static instability patterns is possible by physical examination. This review article presents the ligaments of the thumb and the fingers, the traumatic and degenerative lesions as well as the diagnostic capability of x­rays, cinematography, magnetic resonance imaging (MRI) and MR arthrography.

Injuries of the scapholunate and lunotriquetral ligaments as well as the TFCC in intra-articular distal radius fractures. Prevalence assessed with MDCT arthrography.

OBJECTIVES: To evaluate the prevalence of injuries of the scapholunate and lunotriquetral interosseous ligaments (SLIL, LTIL) as well as the triangular fibrocartilage complex (TFCC) in intra-articular distal radius fractures (iaDRF). METHODS: Two hundred and thirty-three patients with acute iaDRF underwent MDCT arthrography. The SLIL and LTIL were described as normal, partially or completely ruptured. Major injuries of the SLIL were defined as completely ruptured dorsal segments, those of the LTIL as completely ruptured palmar segments. The TFCC was judged as normal or injured. Interobserver variability was calculated. Injury findings were correlated with the types of iaDRF (AO classification). RESULTS: In 159 patients (68.2 %), no SLIL injuries were seen. Minor SLIL injuries were detected in 54 patients (23.2%), major injuries in 20 patients (8.6%). No correlation was found between the presence of SLIL lesions and the types of iaDRF. Minor LTIL injuries were seen in 23 patients (9.9%), major injuries in only 5 patients (2.2%). The TFCC was altered in 141 patients (60.5%). Interobserver variability was high for MDCT arthrography in assessing SLIL and TFC lesions, and fair for LTIL lesions. CONCLUSION: In iaDRF, prevalence of major injuries of the most relevant SLIL is about 9% as evaluated with CT arthrography. KEY POINTS: The C-shaped SLIL is built of dorsal, middle and palmar segments. In iaDRF, major SLIL injuries are associated in 8.6% of the cases. In iaDRF, the SLIL remains intact in 68.3% of the cases. IaDRF and SLIL ruptures can comprehensively be depicted with MDCT arthrography. A three-compartment approach is recommended to assess intrinsic ligaments and the TFCC.

[Ligament injuries of the wrist]. / Bandverletzungen an der Handwurzel.

The distal radioulnar joint, the triangular fibrocartilage complex (TFCC) and the wrist are stabilized by many ligaments allowing not only a wide range of motion but also providing sufficient stability. The complex arrangement of carpal ligaments and prosupination around the forearm joint enables multiaxial motion patterns. In the wrist, intra-articular ligaments can be differentiated from extra-articular capsular ligaments as well as intrinsic and extrinsic ligament courses. Imaging is essential for classification of dynamic and static instability patterns. This review article illustrates the ligamentous anatomy of the wrist, the symptoms of carpal instability as well as the diagnostic capability of projection radiography, cinematography, computed tomography (CT) arthrography, magnetic resonance imaging (MRI) and MR arthrography.

[Acute scaphoid fractures : Management under consideration of the new S3-level guideline]. / Die frische Skaphoidfraktur : Management unter Berücksichtigung der neuen S3-Leitlinie.

BACKGROUND: Scaphoid fractures represent the most common carpal fractures and are often problematic and frequently lead to nonunion with osteoarthritis and collapse of the wrist. The reasons for the nonunion are manifold. Therefore, the main goal of diagnosis and therapy of acute fractures is to achieve bony union and to restore the anatomic shape of the scaphoid. In the long run, only this can preserve the normal function of the wrist. METHODOLOGY: The given recommendations are based on the new S3-level guideline of the AWMF (Association of the Scientific Medical Societies). This guideline was established with involvement of all relevant medical societies based on a comprehensive and systematic review of the literature and after a process of formal consent. The focus of the guideline is recommendations regarding diagnosis and therapy of acute scaphoid fractures. MAIN STATEMENTS: After careful clinical examination consequent imaging must be performed, starting with X­rays in three standard projections. Computed tomography is indispensable for proof of a fracture and for therapy planning. The classification of Herbert and Krimmer is based on the CT under special consideration of instability and displacement of the fracture. Thus, indication for operative and non-operative treatment is mainly CT-dependent. Non-operative treatment may be indicated only for stable fractures (type A). However, operative treatment is strongly recommended for all unstable fractures (type B). For fixation, double-threaded headless screws are preferred. The operative technique depends on the fracture morphology. CONCLUSION: Diagnosis and therapy of acute scaphoid fractures are primarily aimed at the prevention of nonunion and arthritic carpal collapse with painful impairment of the wrist function. To achieve this, the S3-level guideline contains explicit recommendations.

[Chronic kidney disease : What is currently available for treatment?] / Chronische Niereninsuffizienz : Was ist gesichert in der Therapie?

Chronic kidney disease is common in the general population with an estimated prevalence of roughly 2 million in Germany. Typically, chronic kidney disease is progressive and in the terminal stage the patients require dialysis or kidney transplantation. In many cases the disease remains silent for a long time but early stages are already associated with increasing morbidity and mortality. Therefore early detection is very important. In recent years several new concepts have been introduced that might help to slow the progression of chronic kidney disease or improve the accompanying risks. Here, we want to provide a nephrologist's perspective on the current guidelines for the treatment and prevention of chronic kidney disease. We summarize which diagnostic approaches are useful for general practitioners and we take a pragmatic look at the existing opportunities for combating renal functional decline. We also shed light on established measures to minimize the risk of comorbidities.

[Hyperkalemia : what can we expect from new potassium-lowering drugs?]. / Hyperkaliämie : Was dürfen wir von den neuen Kaliumsenkern erwarten?

Hyperkalemia is a common clinical problem. While several options are available to treat acute hyperkalemia, there are few options for long-term treatment. The use of oral potassium binders might be such an option. Sodium zirconium cyclosilicate and patiromer are two new oral potassium binders awaiting approval. The efficacy of these novel potassium-lowering agents were tested in several phase 3 short-term studies published in late 2014.

[Scapholunate lesions]. / Die skapholunäre Bandverletzung.

Injuries to the scapholunate ligament are the most frequent cause of carpal instability. Therefore, if a scapholunate lesion is not diagnosed, it may result in a severe dysfunction of the wrist. This review describes the anatomy, and the kinematics of the wrist with an intact as well as a disrupted scapholunate ligament. The diagnostic of an isolated ligament lesion and a ligament injury associated with a fracture of the distal radius is presented. Finally, an algorithm for treatment based on the stage of injury is proposed.