Therefore, in the current manuscript the authors aim to review th

Therefore, in the current manuscript the authors aim to review the most important topics related to this pathological presentation.”
“Microarrays of peptide and recombinant protein libraries are routinely used for high-throughput studies of protein-protein interactions and enzymatic activities. Imaging mass spectrometry (IMS) is

currently applied as a method to localize analytes on thin tissue sections and other surfaces. Here, we have applied IMS as a label-free means to analyze protein-peptide interactions in a microarray-based phosphatase assay. This IMS strategy visualizes the entire microarray in one composite image by collecting a predefined raster of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry 3-MA inhibitor spectra over

the surface of the chip. Examining the bacterial tyrosine phosphatase YopH, we used IMS as a label-free means to visualize enzyme binding PF-00299804 clinical trial and activity with a microarrayed phosphopeptide library printed on chips coated with either gold or indium-tin oxide. Furthermore, we demonstrate that microarray-based IMS can be coupled with surface plasmon resonance imaging to add kinetic analyses to measured binding interactions. The method described here is within the capabilities of many modern MALDI-TOF instruments and has general utility for the label-free analysis of microarray assays. Published by Elsevier Inc.”
“The aging process involves changes in immune regulation, i.e. adaptive immunity declines whereas innate immunity becomes activated. NF-kappa B signaling is the master regulator of the both immune systems. Two recent articles highlight the role of the NF-kappa B system in aging and immune responses. Adler et al((1)) showed that the NF-kappa B binding domain is the genetic regulatory motif which is most strongly associated with the aging process. Kwon et al((2)) studying HIV-1 infection and subsequent immune deficiency process demonstrated that HIV-1 Tat protein binds

to SIRT1 protein, a well-known longevity factor, and inhibits the SIRT-1-mediated deacetylation of the p65 LY3023414 purchase component of the NF-kappa B complex. As a consequence, the transactivation efficiency of the NF-kappa B factor was greatly potentiated, leading to the activation of immune system and later to the decline of adaptive immunity. These observations support the scenario where immune responses and aging process can be enforced by the potentiation of NF-kappa B transactivation efficiency. Longevity factors, such as SIRT1 and its activators, might regulate the efficiency of the NF-kappa B signaling, the major outcome of which is inflamm-aging via proinflammatory responses. BioEssays 29:939-942, 2008. (C) 2008 Wiley Periodicals, Inc.”
“Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor that was related to cancer development and metastasis dissemination on several types of tumors. However, it is not known the effect of SLPI on mammary and colon tumors.

335) Conclusion Despite

some heterogeneity there is

335).\n\nConclusion. Despite

some heterogeneity there is a possible indication of an association between RS and patients receiving interferons. [Int Angiol 2012;31:408-13]“
“Benzophenanthridine alkaloids (chelerythrine and sanguinarine) inhibited binding of [H-3]SR141716A to mouse brain membranes (IC(50)s: smaller than 1 mu M). Piperonyl butoxide and (S)-methoprene were less potent (IC(50)s: 21 and 63 mu M respectively). Benzophenanthridines and piperonyl butoxicle were more selective towards brain CB1 receptors versus spleen CB2 receptors. All compounds reduced B-max of [H-3]SR141716A binding to CB1 receptors, but only methoprene and piperonyl butoxide increased www.selleckchem.com/products/pu-h71.html K-d (3-5-fold). Benzophenanthridines increased the K-d of [H-3]CP55940 binding (6-fold), but did not alter B-max. (S)methoprene increased the K-d of [H-3]CP55940 binding (by almost 4-fold) and reduced B-max by 60%. Piperonyl butoxicle lowered Selleck Compound C the B-max of [H-3]CP55940 binding by 50%, but did not influence K-d. All compounds reduced [H-3]SR141716A and [H-3]CP55940 association with CBI receptors. Combined with a saturating concentration of SR141716A, only piperonyl butoxide and

(S)-methoprene increased dissociation of [H-3]SR141716A above that of SR141716A alone. Only piperonyl butoxicle increased dissociation of [H-3]CP55940 to a level greater than CP55940 alone. Binding results indicate predominantly allosteric components to the study compounds action. 4-Aminopyridine-(4-AP-) evoked release of L-glutamate from synaptosomes was partially inhibited by WIN55212-2, an effect completely neutralized by AM251, (s) methoprene and piperonyl butoxide. With WIN55212-2 present, benzophenanthridines enhanced 4-AP-evoked L-glutamaterelease above 4-AP alone. Modulatory patterns of L-glutamate release (with WIN-55212-2

present) align with previous antagonist/inverse agonist profiling based on [S-35]GTP gamma S binding. Although these compounds exhibit lower potencies compared to many classical CB1 receptor inhibitors, they may have potential to modify CB1-receptor-dependent behavioral/physiological outcomes in the check details whole animal. (C) 2013 Elsevier B.V. All rights reserved”
“Background/purpose: Pressable all-ceramic materials are widely used in dentistry. Determining the effect of repeated firing on flexural strength will help to improve these materials so that they can remain resistant to fracture in restorative work. The aim of this study was to determine the change in the flexural strength of pressable all-ceramic materials after repeated firings, which may be unavoidable when color and shape corrections are necessary for use in dental restorations. Materials and methods: Forty disc specimens (15.5 mm x 2.1 mm) were prepared for each of four pressable ceramic materials (Empress 2, Finesse, Cergo, and Evopress) according to the manufacturers’ instructions.

Production of IFN-gamma was decreased and IL-2 was increased from

Production of IFN-gamma was decreased and IL-2 was increased from ConA stimulated flight splenocytes. This study demonstrated that expression of surface molecules can be affected by conditions of spaceflight and impaired responsiveness persists SHP099 chemical structure under culture conditions in vitro.”
“The RNA-mediated disease model for myotonic dystrophy (DM) proposes that microsatellite C(C)TG expansions express toxic RNAs that disrupt splicing regulation by altering MBNL1 and CELF1 activities. While this model

explains DM manifestations in muscle, less is known about the effects of C(C)UG expression on the brain. Here, we report that Mbnl2 knockout mice develop several DM-associated central nervous system (CNS) features including abnormal REM sleep propensity and deficits in spatial memory. Mbnl2 is prominently expressed in the hippocampus and Mbnl2 knockouts show a decrease in NMDA receptor (NMDAR) synaptic transmission and impaired hippocampal synaptic plasticity. While Mbnl2 loss did not significantly alter target transcript levels in the hippocampus, misregulated splicing of hundreds of exons was detected using splicing microarrays, RNA-seq, and HITS-CLIP. Importantly, the majority of the

Mbnl2-regulated exons examined GSK2118436 were similarly misregulated in DM. We propose that major pathological features of the DM brain result from disruption of the MBNL2-mediated developmental splicing program.”
“In the view of transmutation of transuranium ( TRU) elements, molten salt fast reactors (MSFRs) offer certain advantages compared to solid fuelled reactor types like sodium cooled fast reactors (SFRs). In the first part these advantages are discussed in comparison with the SFR technology, and the research challenges are analyzed. In the second part cycle studies for the MSFR are given for different configurations – a core with U-238 fertile, a fertile free core, and a core with Th-232 as fertile material. For all

cases, the transmutation potential is determined and efficient transmutation performance for the case with thorium as a fertile material as well as for the fertile free case is demonstrated and the individual advantages are discussed. The time evolution Crenigacestat purchase of different important isotopes is analyzed. In the third part a strategy for the optimization of the transmutation efficiency is developed. The final aim is dictated by the phase out decision of the German government, which requests to put the focus on the determination of the maximal transmutation efficiency and on an as much as possible reduced leftover of transuranium elements at the end of the reactor life. This minimal leftover is achieved by a two step procedure of a first transmuter operation phase followed by a second deep burning phase. There the U-233, which is bred in the blanket of the core consisting of thorium containing salt, is used as feed.

Therefore, to obtain

Therefore, to obtain WH-4-023 order perfect transcriptions, heavy human intervention is required to validate and correct the results of such systems. Given that this post-editing process is inefficient and uncomfortable, a multimodal interactive approach has been proposed in previous works, which aims at obtaining correct transcriptions with the minimum human effort. In this approach, the user interacts with the system by means of an e-pen and/or more traditional

methods such as keyboard or mouse. This user’s feedback allows to improve system accuracy and multimodality increases system ergonomics and user acceptability. Until now, multimodal interaction has been considered only at whole-word level. In this work, multimodal interaction at character-level is studied, that may lead to more effective interactivity,

since it is faster and easier to write only one character rather than a whole word. Here we study this kind of fine-grained multimodal interaction and present developments that allow taking advantage of interaction-derived context to significantly improve feedback decoding accuracy. Empirical tests on three cursive handwritten tasks suggest that, despite losing the deterministic accuracy of traditional peripherals, this approach can save significant amounts of user effort with respect to fully manual transcription as well as to noninteractive post-editing correction.”
“A number of interspinous devices (ISD) have been introduced in the lumbar spine implant market. Unfortunately, the use of these devices often is not associated with real comprehension of their biomechanical role. The aim of this paper is to review the biomechanical CHIR98014 nmr studies about interspinous devices available in the literature to allow the reader a better comprehension of the effects of these devices on Taselisib inhibitor the treated segment and on the adjacent segments of the spine. For this reason, our analysis will be limited to the interspinous devices that have biomechanical studies published in

the literature.”
“An injectable composite gel was developed from alginic and hyaluronic acid. The enzymatically cross-linked injectable gels were prepared via the oxidative coupling of tyramine modified sodium algiante and sodium hyaluronate in the presence of horse radish peroxidase (HRP) and hydrogen peroxide (H2O2). The composite gels were prepared by mixing equal parts of the two tyraminated polymer solutions in IOU HRP and treating with 1.0% H2O2. The properties of the alginate gels were significantly affected by the addition of hyaluronic acid. The percentage water absorption and storage modulus of the composite gels were found to be lower than the alginate gels. The alginate and composite gels showed lower protein release compared to hyaluronate gels in the absence of hyaluronidase. Even hyaluronate gels showed only approximately 10% protein release after 14 days incubation in phosphate buffer solution. ATDC-5 cells encapsulated in the injectable gels showed high cell viability.

The therapeutic approach is

the same as for idiopathic ca

The therapeutic approach is

the same as for idiopathic cardiomyopathy and in this context it is absolutely necessary selleck compound to show caution concerning the state of pregnancy and the resulting contraindications for therapeutic drugs. The prognosis is dependent on recovery from the heart failure during the first 6 months postpartum. The lethality of the disease is high and is given in the literature as up to 28 %. Because of its complexity PPCM is an interdisciplinary challenge. In the peripartum phase a close cooperation between the disciplines of cardiology, cardiac surgery, neonatology, obstetrics and anesthesiology is indispensable. For anesthesiology the most important aspects are the mostly advanced unstable hemodynamic condition of the mother and the planning and implementation of the perioperative management. This article

presents the case of a patient in advanced pregnancy with signs of acute severe heart failure and a suspected diagnosis of PPCM. The patient presented as an emergency case and delivery of the child was carried out using peridural anesthesia with a stand-by life support machine.”
“Population cycles are mostly thought to arise through extrinsic rather than intrinsic processes. However, in red grouse (Lagopus lagopus scoticus), intrinsic male territoriality has been proposed as a driver of the cycles, possibly in conjunction with an extrinsic interaction CX-6258 with specialist parasitic worms. Here we examine how harvesting and environmental noise may also interact with territoriality to determine how grouse populations cycle.\n\nA stochastic model of grouse

dynamics based on the territoriality hypothesis is developed, including harvesting and the effects of nonterritorial birds on aggressiveness. Cycles are detected in 97% of populations simulated over realistic parameter ranges, and these exhibit Fludarabine mouse similar statistical properties to those reported in studies of multiple grouse populations. As observed, cycle periods are shorter at higher breeding productivities.\n\nThe model demonstrates the destabilizing influence of delayed density-dependent territorial aggressiveness. Cycle amplitudes are higher when annual changes in aggression are larger and when nonterritorial males provoke greater aggression. Intriguingly, the model suggests how an interaction between aggressiveness and parasites may operate. It is known that males with high worm burdens show dramatic decreases in aggressiveness in the year following a peak in territoriality. When this is included in the model, via larger crashes in aggression, amplitudes are higher, despite a reduction in overall aggressiveness.\n\nEnvironmental stochasticity interacts with territoriality to determine the form of the cycles, but this is mediated through its ‘colour’ or temporal autocorrelation. For example, uncorrelated white noise increases amplitudes, while autocorrelated red noise has the opposite effect. However, noise increases cycle periods whatever the colour.

Diffusional

Diffusional this website kurtosis imaging can provide additional and complementary information to DTI on spinal cord pathology.”
“Foot-and-mouth disease (FMD) is a highly contagious, debilitating, and globally significant viral disease typically affecting cloven-hoofed hosts. The diagnosis of FMD in bears in Vietnam is described. The current study describes a confirmed case of FMD in a bear species, and the clinical signs compatible with FMD in a Malayan sun bear.

Thirteen Asiatic black bears (Ursus thibetanus) and 1 Malayan sun bear (Helarctos malayanus) were apparently affected. In August 2011, an adult bear became lethargic, and developed footpad vesicles. Over 15 days, 14 out of 17 bears developed similar signs; the remaining 3 co-housed bears and another 57 resident bears did not. All affected bears developed vesicles on all footpads, and most were lethargic for 24-48 hr. Nasal and oral lesions were noted in 6 and 3 cases, respectively. Within 1 month, all looked normal. Foot-and-mouth disease virus (FMDV) was detected by reverse transcription polymerase chain reaction, classified as serotype O, and isolated by virus isolation techniques. Phylogenetic analysis Rabusertib inhibitor demonstrated clustering of 3 bear isolates, in a branch distinct from other FMDV type O isolates. The outbreak likely occurred due to indirect contact with livestock,

and was facilitated by the high density of captive bears. It showed that Asiatic black bears are capable of contracting FMDV and developing clinical disease, and that the virus spreads easily between bears in close contact.”
“Controlled wear testing of total hip replacements in hip joint simulators is a well-established and powerful method, giving an extensive prediction of the long-term Y-27632 mw clinical performance. To understand the wear behavior of a bearing and its limits under in vivo conditions, testing scenarios should be designed as physiologically as possible. Currently, the ISO standard protocol 14242 is the most common preclinical testing procedure for total hip replacements, based on a simplified gait cycle for normal walking conditions. However, in recent years, wear patterns have increasingly

been observed on retrievals that cannot be replicated by the current standard. The purpose of this study is to review the severe testing conditions that enable the generation of clinically relevant wear rates and phenomena. These conditions include changes in loading and activity, third-body wear, surface topography, edge wear and the role of aging of the bearing materials.”
“The epidemiological transition has produced a society with a growing number of the elderly affected by multiple chronic diseases which often requires polypharmacy. Despite being the main users of medications, the elderly are largely underrepresented in clinical trials, especially if they have multimorbidity. It follows that the results of these trials are not applicable in the real world and potentially harmful.

J Neurophysiol 108: 1473-1483, 2012 First published June 6, 2012

J Neurophysiol 108: 1473-1483, 2012. First published June 6, 2012; doi:10.1152/jn.00825.2011.-Previously we demonstrated that sphingosine 1-phosphate receptor 1 (S1PR(1)) played a prominent, but not exclusive, role in enhancing the excitability of small-diameter sensory neurons, suggesting that other S1PRs can modulate neuronal excitability. Sotrastaurin supplier To examine the potential role of S1PR(2) in regulating neuronal excitability we used the established selective antagonist of S1PR(2), JTE-013. Here we report that exposure

to JTE-013 alone produced a significant increase in excitability in a time- and concentration-dependent manner in 70-80% of recorded neurons. Internal perfusion of sensory neurons with guanosine 5′-O-(2-thiodiphosphate) (GDP-beta-S) via the recording pipette inhibited the sensitization produced by JTE-013 as well as prostaglandin E-2. Pretreatment with pertussis toxin or the selective S1PR(1) antagonist W146 blocked the sensitization produced by JTE-013. These results indicate that JTE-013 might act as an agonist at other G protein-coupled receptors. In neurons that were sensitized by JTE-013, single-cell RT-PCR studies demonstrated that these neurons did not express the mRNA for S1PR(2). In behavioral studies, injection of JTE-013 into the rat’s hindpaw produced a significant increase in the mechanical sensitivity in the

ipsilateral, but not contralateral, paw. Injection of JTE-013 did not affect buy LY2090314 the withdrawal latency to thermal stimulation.

Thus JTE-013 augments neuronal excitability independently of S1PR(2) IPI-145 mouse by unknown mechanisms that may involve activation of other G protein-coupled receptors such as S1PR(1). Clearly, further studies are warranted to establish the causal nature of this increased sensitivity, and future studies of neuronal function using JTE-013 should be interpreted with caution.”
“Venoms of brown spiders in the genus Loxosceles contain phospholipase D enzyme toxins that can cause severe dermonecrosis and even death in humans. These toxins cleave the substrates sphingomyelin and lysophosphatidylcholine in mammalian tissues, releasing the choline head group. The other products of substrate cleavage have previously been reported to be monoester phospholipids, which would result from substrate hydrolysis. Using P-31 NMR and mass spectrometry we demonstrate that recombinant toxins, as well as whole venoms from diverse Loxosceles species, exclusively catalyze transphosphatidylation rather than hydrolysis, forming cyclic phosphate products from both major substrates. Cyclic phosphates have vastly different biological properties from their monoester counterparts, and they may be relevant to the pathology of brown spider envenomation.”
“Hyperosmotic stress has been widely explored as a means of improving specific antibody productivity in mammalian cell cultures.

seizures in the elderly tend, however, to respond better

seizures in the elderly tend, however, to respond better

HSP990 datasheet to antiepileptic drugs than those in younger individuals, and can often be appropriately controlled with monotherapy. After the diagnosis of epilepsy is confirmed, treatment should be started with a single medication at a low dose, with subsequent gradual upward titration until seizures are controlled. First-generation antiepileptic drugs should be avoided in the elderly in view of poor tolerability. A large trial has shown that lamotrigine and gabapentin are better tolerated than carbamazepine. in elderly patients whose seizures remain uncontrolled on antiepileptic medications, surgery can be considered if excellent results are predicted and the risks are low.”
“Multiple sclerosis affects young and middle-aged people and often leads to physical and cognitive handicaps. There is a need for detailed knowledge of the social consequences of the disease. We aim here to describe the course of the working life and career of multiple sclerosis patients at selleck products the time of onset and thereafter, in terms of probability of early pension and income development.\n\nAll 2538 patients with multiple sclerosis in Denmark with disease onset between

1980 and 1989, identified through the Danish MS-Registry, were included in this study. Twenty matched control persons per patient were randomly drawn from the civil registration

system. Information on economic status was retrieved from Statistics Denmark. A survival analysis technique was used with onset as the starting point. We found that the probability of remaining without early pension was at 5 years 70% for patients and 97% for controls, and at 20 years 22% for patients and 86% for controls. Due to lower rates for early pension, gross income with time was lower in patients than controls. We conclude that multiple sclerosis seriously affects the economic life of multiple sclerosis patients, even within a few years of onset.”
“Spatial health inequalities have often been analyzed Selleckchem Mocetinostat in terms of socioeconomic and environmental factors. The present study aimed to evaluate spatial relationships between spatial data collected at different spatial scales. The approach was illustrated using health outcomes (mortality attributable to cancer) initially aggregated to the county level, district socioeconomic covariates, and exposure data modeled on a regular grid. Geographically weighted regression (GWR) was used to quantify spatial relationships. The strongest associations were found when low deprivation was associated with lower lip, oral cavity and pharynx cancer mortality and when low environmental pollution was associated with low pleural cancer mortality.

Moreover, except alpha-pinene and linalool, the other three compo

Moreover, except alpha-pinene and linalool, the other three compounds as well as the essential oil exhibited comparable repellency against the booklouse relative to DEET. (C) 2014 The Authors.”
“Background: Improved early outcome in non-ST elevation myocardial infarction (NSTEMI) patients has been mainly attributed to a broader use of

invasive strategies. Little is known click here about the impact of other changes in early management. Methods: We aimed to assess 15-year trends in one-year mortality and their determinants in NSTEMI patients. We used data from 4 one-month French registries, conducted 5 years apart from 1995 to 2010 including 3903 NSTEMI patients admitted to intensive care units. Results: From 1995 to 2010, no major change was observed in patient characteristics, while therapeutic management evolved considerably. Early use of antiplatelet agents, beta-blockers, ACE-inhibitors and statins increased over time (P smaller than 0.001); use of newer anticoagulants (low-molecular-weight heparin, bivalirudin or fondaparinux) increased from 40.8% in 2000 to 78.9% in 2010 (P smaller than 0.001); percutaneous coronary intervention (PCI) smaller than = 3 days of admission rose from 7.6% to 48.1% (P smaller than 0.001). One-year death decreased from 20% to 9.8% (HR adjusted for baseline parameters, 2010 vs. 1995 = 0.47, 95% CI: 0.35-0.62). Early PCI (HR

= 0.67; 95% CI: 0.49-0.90), use of newer anticoagulants (HR = 0.62; 95% CI: 0.48-0.78) and early use of evidence based GPCR Compound Library medical therapy (HR = 0.54; 95% CI: 0.40-0.72) were predictors of improved one year-survival.

Conclusions: One-year mortality of NSTEMI patients decreased by 50% in the past 15 years. Our data support current guidelines recommending early invasive strategies and use of newer anticoagulants INCB018424 cost for NSTEMI, and also show a strong positive association between early use of appropriate medical therapies and one-year survival, suggesting that these medications should be used from the start. (C) 2014 Elsevier Ireland Ltd. All rights reserved.”
“The present ultrastructural study on follicle of regenerating feathers of four different avian species focuses on the formation and cytology of the rachis. Epithelial cells within the bottom part of the follicle (the collar) are contacted from mesenchymal cells of the dermal papilla. The most basal part of the collar is formed by a circular epithelium containing germinal cells, while in the upper ramogenic part of the collar barb ridges are generated. Epithelial cells rest upon a basement membrane that is stretched in actively forming barb ridges among which anchored mesenchymal cells send thin elongation. This observation suggests that an intense exchange of molecules with the epithelium occurs. The process of formation of the rachis occurs by fusion of barb ridges with the nonsegmented, dorsal or anterior part of the collar.

It is now generally accepted that BC is the consequence of contin

It is now generally accepted that BC is the consequence of continued BCR-ABL activity leading to genetic instability,

DNA damage, and impaired DNA repair. Most patients with BC carry multiple mutations, and up to 80% show additional chromosomal aberrations in a nonrandom pattern. Treatment with tyrosine kinase inhibitors has improved survival in BC modestly, but most long-term survivors are those who have been transplanted. Patients in BC should be treated with a tyrosine kinase inhibitor according to mutation profile, with or without chemotherapy, with the goal of achieving a second chronic phase and proceeding to allogeneic stem cell transplantation as quickly as possible. Although long-term remissions are rare, allogeneic stem cell transplantation provides the best chance of a cure in BC. Investigational agents are not

likely to provide an alternative in the near future. In view of these limited #432 randurls[1|1|,|CHEM1|]# options, prevention of BC by a rigorous and early elimination of BCR-ABL is recommended. Early response indicators should be used to select patients for alternative therapies and early transplantation. Every attempt should be made to reduce or eliminate BCR-ABL consistent with good patient care as far as possible. (Blood. 2012; 120(4):737-747)”
“Background/Aims: Primary gastrointestinal follicular lymphoma (GI-FL) is very rare and its natural course is barley known. This study aimed to evaluate the clinical characteristics of primary gastrointestinal follicular lymphoma (GI-FL). Methodology: From

May 1996 to October 2008, the records of five patients buy MI-503 diagnosed with primary GI-FL were retrieved from pathological files WH-4-023 supplier and retrospectively analyzed in terms of characteristics of endoscopic and clinical findings. Results: The five patients consisted of 3 males and 2 females with a median age of 52 years. Abdominal pain was the most common (n=4, 80%) symptom. The most frequent site was the terminal ileum in the small bowel (n=3, 60%). Endoscopic findings were 3 of mass forming type, 1 of irregular ulcer type and 1 of whitish granular type. Three cases (60%) had a component of diffuse large B cell lymphoma. All cases received chemotherapy. While complete remission occurred in every patient, relapse occurred in the two patients with a higher grade and more advanced stage than the other cases. At a median follow-up time of 37 months (range, 27-58 months; mean, 38.8 months), four patients (80%) were disease-free and one patient had died of cardiovascular disease. Conclusions: In South Korea, primary gastrointestinal follicular lymphoma is very rare and symptomatic. Endoscopic findings were variable from early whitish granular lesions to advanced mass forming lesions.”
“Many topical treatments for cutaneous warts exist and previous reviews of trials did not follow intention-to-treat (ITT) principles for analysis.