SummaryBackgroundFemoroacetabular impingement syndrome is an important cause of hip pain in young adults. It can be treated by arthroscopic hip surgery, including reshaping the hip, or with physiotherapist-led conservative care. We aimed to compare the clinical effectiveness of hip arthroscopy with best conservative care.MethodsUK FASHIoN is a pragmatic, multicentre, assessor-blinded randomised controlled trial, done at 23 National Health Service hospitals in the UK. We enrolled patients with femoroacetabular impingement syndrome who presented at these hospitals. Eligible patients were at least 16 years old, had hip pain with radiographic features of cam or pincer morphology but no osteoarthritis, and were believed to be likely to benefit from hip arthroscopy. Patients with bilateral femoroacetabular impingement syndrome were eligible; only the most symptomatic hip was randomly assigned to treatment and followed-up. Participants were randomly allocated (1:1) to receive hip arthroscopy or personalised hip therapy (an individualised, supervised, and progressive physiotherapist-led programme of conservative care). Randomisation was stratified by impingement type and recruiting centre and was done by research staff at each hospital, using a central telephone randomisation service. Patients and treating clinicians were not masked to treatment allocation, but researchers who collected the outcome assessments and analysed the results were masked. The primary outcome was hip-related quality of life, as measured by the patient-reported International Hip Outcome Tool (iHOT-33) 12 months after randomisation, and analysed in all eligible participants who were allocated to treatment (the intention-to-treat population). This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN64081839, and is closed to recruitment.FindingsBetween July 20, 2012, and July 15, 2016, we identified 648 eligible patients and recruited 348 participants: 171 participants were allocated to receive hip arthroscopy and 177 to receive personalised hip therapy. Three further patients were excluded from the trial after randomisation because they did not meet the eligibility criteria. Follow-up at the primary outcome assessment was 92% (319 of 348 participants). At 12 months after randomisation, mean iHOT-33 scores had improved from 39·2 (SD 20·9) to 58·8 (27·2) for participants in the hip arthroscopy group, and from 35·6 (18·2) to 49·7 (25·5) in the personalised hip therapy group. In the primary analysis, the mean difference in iHOT-33 scores, adjusted for impingement type, sex, baseline iHOT-33 score, and centre, was 6·8 (95% CI 1·7–12·0) in favour of hip arthroscopy (p=0·0093). This estimate of treatment effect exceeded the minimum clinically important difference (6·1 points). There were 147 patient-reported adverse events (in 100 [72%] of 138 patients) in the hip arthroscopy group) versus 102 events (in 88 [60%] of 146 patients) in the personalised hip therapy group, with muscle soreness being the most common of the...

Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.

The hydraulic conductivity of excised roots (Lp(r)) of the legume Lotus japonicus (Regel) K. Larsen grown in mist (aeroponic) and sand cultures, was found to vary over a 5-fold range during a day/night cycle. This behaviour was seen when Lp(r) was measured in roots exuding, either under root pressure (osmotic driving force), or under an applied hydrostatic pressure of 0.4 MPa which produced a rate of water flow similar to that in a transpiring plant. A similar daily pattern of variation was seen in plants grown in natural daylight or in controlled-environment rooms, in plants transpiring at ambient rates or at greatly reduced rates, and in plants grown in either aeroponic or sand culture. When detached root systems were connected to a root pressure probe, a marked diurnal variation was seen in the root pressure generated. After excision, this circadian rhythm continued for some days. The hydraulic conductivity of the plasma membrane of individual root cells was measured during the diurnal cycle using a cell pressure probe. Measurements were made on the first four cell layers of the cortex, but no evidence of any diurnal fluctuation could be found. It was concluded that the conductance of membranes of endodermal and stelar cells may be responsible for the observed diurnal rhythm in root Lp(r). When mRNAs from roots were probed with cDNA from the Arabidopsis aquaporin AthPIP1a gene, an abundant transcript was found to vary in abundance diurnally under high-stringency conditions. The pattern of fluctuations resembled closely the diurnal pattern of variation in root Lp(r). The plasma membranes of root cells were found to contain an abundant hydrophobic protein with a molecular weight of about 31 kDa which cross-reacted strongly to an antibody raised against the evolutionarily conserved N-terminal amino acid sequence of AthPIP1a.

Abstract. The sap flow (Jv) and the osmotic hydraulic conductance (Lo) of detached, exuding root systems from wheat (Triticum aestivurn L. cv. Chinese Spring) plants deprived of nitrogen for 5 d (-N) or of phosphorus for 7 d (-P), were measured and compared with controls receiving a complete nutrient supply. In the roots of -N and -P plants, Jv and L0 decreased markedly, but between 4 and 24 h after resupplying N to --N plants (NRS plants) and P to -P plants (PRS plants), Jv and Lo recovered to values similar to those of control plants.Values of Jv and Lo were always greater during the light period than during the dark, due to the diurnal variation of these parameters. Reducing transpiration in the light had no effect on Jv and Lo of -N and -P plants. Sap flow and Lo were also determined using individual axes from plants which had been grown with their roots divided between nutrient-deficient ( -N or -P) solution and a complete nutrient solution. Differences were observed in Jv and L0 between axes of the same plant, but stomatal conductance (Gs), which was also measured, was not affected in these split-root experiments. In control plants, Jv and Lo declined sharply to values similar to those of roots from -N and -P plants after HgC12 treatment (50 gM), but were restored by treating with 5 mM dithiothreitol. In plasma membranes from -N and -P roots, the amount of stigmasterol increased relative to sitosterol compared with control roots. The degree of unsaturation of bound fatty acids also increased, compared with controls, as a result of a decline in the relative amounts of 16:0 and 18:0 and an increase in 18:2. Plasma-membrane fluidity, estimated by steadystate fluorescence polarisation using 1,6-diphenyl hexatriene, showed that the plasma membranes from nutrient-deprived plants were less fluid than those from control plants, measured during both the light and dark periods and in split-root experiments. In NRS plants, the relative abundance of sitosterol increased, so that the stigmasterol/sitosterol ratio returned to a value similar to that of controls. However, in PRS plants, the difference in stigmasterol/sitosterol ratio was maintained, compared with controls. The degree of unsaturation of bound fatty acids, membrane fluidity and the hydraulic conductivity of root systems also recovered in NRS and PRS plants to values similar to those of control plant plasma membranes. The results obtained suggested that -N and -P treatment decreased L0, by reducing either the activity or the abundance of Hg-sensitive water channels. Also, there may be an interaction between the increase in membrane lipid ordering and the decrease in Lo.

It has been shown that N-, P- and S-deficiencies result in major reductions of root hydraulic conductivity (Lpr) which may lead to lowered stomatal conductance, but the relationship between the two conductance changes is not understood. In a variety of species, Lpr decreases in the early stages of NO3-, H2PO4(2-) and SO4(2-) deprivation. These effects can be reversed in 4-24 h after the deficient nutrient is re-supplied. Diurnal fluctuations of root Lpr have also been found in some species, and an example of this is given for Lotus japonicus. In nutrient-sufficient wheat plants, root Lpr is extremely sensitive to brief treatments with HgCl2; these effects are completely reversible when Hg is removed. The low values of Lpr in N- or P-deprived roots of wheat are not affected by Hg treatments. The properties of plasma membrane (PM) vesicles from wheat roots are also affected by NO3(-)-deprivation of the intact plants. The osmotic permeability of vesicles from N-deprived roots is much lower than that of roots adequately supplied with NO3-, and is insensitive to Hg treatment. In roots of L. japonicus, gene transcripts are found which have a strong homology to those encoding the PIP1 and PIP2 aquaporins of Arabidopsis. There is a very marked diurnal cycle in the abundance of mRNAs of aquaporin gene homologues in roots of L. japonicus. The maxima and minima appear to anticipate the diurnal fluctuations in Lpr by 2-4 h. The temporal similarity between the cycles of the abundance of the mRNAs and root Lpr is most striking. The aquaporin encoded by AtPIP1 is known to have its water permeation blocked by Hg binding. The lack of Hg-sensitivity in roots and PMs from N-deprived roots provides circumstantial evidence that lowered root Lpr may be due to a decrease in either the activity of water channels or their density in the PM. It is concluded that roots are capable, by means completely unknown, of monitoring the nutrient content of the solution in the root apoplasm and of initiating responses that anticipate by hours or days any metabolic disturbances caused by nutrient deficiencies. It is the incoming nutrient supply that is registered as deficient, not the plant's nutrient status. At some point, close to the initiation of these responses, changes in water channel activity may be involved, but the manner in which monitoring of nutrient stress is transduced into an hydraulic response is also unknown.