Condensation and smudging of the laparoscope were minimized, impr

Condensation and smudging of the laparoscope were minimized, improving visualization and efficiency. The system allowed for use of suction without significant loss of insufflation pressure.\n\nConclusion: The initial experience with the AirSeal valveless trocar system in LESS is encouraging. This technology may offer significant benefits over traditional laparoscopic trocars and single-port platforms and appears particularly

suited to facilitate LESS.”
“Objective: The modulation of short latency reflex linking Selleck AS1842856 the pretibial to quadriceps muscle (CPQ reflex) was investigated in seven subjects during walking on a treadmill at the stance to swing transition period.\n\nMethodology: The intensity of quadriceps (Q) EMG was increased throughout the gait cycle by using a modified knee orthosis. Pairs of spring were added to the orthosis to produce different levels of muscular activity in Q during the midstance, transition period and terminal swing phase of gait. Electrical stimulation was applied to the common peroneal nerve (CPN) at these three instants of gait.\n\nResults: The peak to peak amplitude of CPQ reflex was significantly increased with escalation of background EMG in Q during midstance (p < 0.015) and terminal swing (p < 0.04). At the transition period

however, despite significant increase in the Q activity no responses was evoked.\n\nConclusions: The results were indicative of an active inhibition of the reflex pathway PI3K inhibitor during transition period. This inhibition could help the unloading of the limb that is necessary for the initiation of the swing phase.”
“Using two ethnographic case studies, the intersecting dynamics of

inequality, morality, and corruption CYT387 price are examined as they play out in Nigerian AIDS NGOs. To the Nigerian public, local AIDS organizations are widely seen as conduits for corruption. But local opinions of particular NGOs and their leaders turn less on whether donor resources were misused and more on the ways that people who accumulate the benefits of corruption use them socially. Nevertheless, discontent swirls about corruption in general, a fact that suggests a gradual change in people’s understandings of the processes that produce inequality in Nigeria. (c) 2011 Elsevier Ltd. All rights reserved.”
“Pre-harvest sprouting (PHS) is one of the most important factors to affect the yield and quality of crops worldwide especially in wet harvest period. Breeding PHS-resistant cultivars has important implications to improve the wheat quality and production. The PHS is determined by environmental conditions, inner factors and interaction between these factors. We here reviewed recent advances influencing factors of PHS, including seed dormancy, seed coat permeability and color, a-amylase activities, endogenous hormones levels, genes and QTLs.

Methods: Two open-label, randomized trials were conducted in

\n\nMethods: Two open-label, randomized trials were conducted in Nimba County, Liberia: i) the main tolerability trial with 1,000 Plasmodium falciparum malaria patients aged over five years (Study-T), and, ii) an efficacy trial with a secondary objective of collecting tolerability

data among 300 children age six to 59 months (Study-E). In both studies patients were randomized to fixed-dose artesunate-amodiaquine (ASAQ Winthrop (R)) or artemether-lumefantrine (AL, Coartem (R)), respectively. Clinical-and laboratory-adverse events (AEs) were recorded until day 28.\n\nResults: Study-T: most patients experienced at least one AE. Severe AEs were few, primarily asymptomatic AG-014699 datasheet blood system disorders or increased liver enzyme values. No treatment or study discontinuation occurred. Mild or moderate fatigue (39.8% vs 16.3%, p < 0.001), vomiting (7.1% vs 1.6%, p < 0.001), nausea (3.2% vs 1.0%, p = 0.01), and anaemia (14.9% vs 9.8%, p = 0.01) were more frequently recorded in the ASAQ versus AL arm. Study-E: mild or moderate AEs were common, including anaemia, fatigue, vomiting or diarrhoea. The few severe events were asymptomatic blood system disorders

and four clinical events (pneumonia, malaria, vomiting and stomatitis).\n\nConclusion: Both ASAQ and AL were well tolerated in patients of all age groups. No unexpected AEs occurred. Certain mild or moderate AEs were more frequent in the ASAQ arm. Standardised safety surveillance should continue for all forms of ACT.”
“In early August

DAPT concentration 2010, lacquer BI 6727 solubility dmso trees (Toxicodendron vernicifluum) severely damaged by a root rot disease were found on plantations in Iwate, Japan. The causal agent was a fungus identified as Rosellinia necatrix, based on morphology and the sequence of the ribosomal DNA internal transcribed spacer region. The fungus was clearly pathogenic on T. vernicifluum root plantings. This report is the first of white root rot on T. vernicifluum.”
“Voltage-gated calcium (Ca-V) channels catalyse rapid, highly selective influx of Ca2+ into cells despite a 70-fold higher extracellular concentration of Na+. How Ca-V channels solve this fundamental biophysical problem remains unclear. Here we report physiological and crystallographic analyses of a calcium selectivity filter constructed in the homotetrameric bacterial Na-V channel Na(V)Ab. Our results reveal interactions of hydrated Ca2+ with two high-affinity Ca2+-binding sites followed by a third lower-affinity site that would coordinate Ca2+ as it moves inward. At the selectivity filter entry, Site 1 is formed by four carboxyl side chains, which have a critical role in determining Ca2+ selectivity. Four carboxyls plus four backbone carbonyls form Site 2, which is targeted by the blocking cations Cd2+ and Mn2+, with single occupancy.


“Most bacterial chromosomes contain homologs of plasmid pa


“Most bacterial chromosomes contain homologs of plasmid partitioning (par) loci. These loci encode ATPases called ParA that are thought to contribute to the mechanical force required

for chromosome and plasmid Epigenetics inhibitor segregation. In Vibrio cholerae, the chromosome II (chrII) par locus is essential for chrII segregation. Here, we found that purified ParA2 had ATPase activities comparable to other ParA homologs, but, unlike many other ParA homologs, did not form high molecular weight complexes in the presence of ATP alone. Instead, formation of high molecular weight ParA2 polymers required DNA. Electron microscopy and three-dimensional reconstruction revealed that ParA2 formed bipolar helical filaments on double-stranded DNA in a sequence-independent manner. These

filaments had a distinct change in Selleckchem GW572016 pitch when ParA2 was polymerized in the presence of ATP versus in the absence of a nucleotide cofactor. Fitting a crystal structure of a ParA protein into our filament reconstruction showed how a dimer of ParA2 binds the DNA. The filaments formed with ATP are left-handed, but surprisingly these filaments exert no topological changes on the right-handed B-DNA to which they are bound. The stoichiometry of binding is one dimer for every eight base pairs, and this determines the geometry of the ParA2 filaments with 4.4 dimers per 120 angstrom pitch left-handed turn. Our findings will be critical for understanding how ParA proteins function in plasmid and chromosome segregation.”
“Our previous study has for the first time demonstrated that atopic dermatitis (AD) patients show enhanced plasma concentrations

of PF4 and beta-TG. In addition, it has been suggested that chemokines may be the markers of AD severity. The aim of this study was to determine whether enhanced platelet activation in active AD withdraws when the disease reaches KU-57788 in vitro the clinical remission stage. Plasma PF-4 and beta-TG concentrations were studied in 10 AD patients and in 23 healthy controls. Patients were examined twice: first, during the active period, and next, during the clinical remission lasting for at least 6 months. Plasma PF-4 and beta-TG concentrations in patients upon AD remission were significantly lower as compared to active AD and did not differ significantly from the healthy subjects. Enhanced platelet activation is a transient phenomenon accompanying active AD and disappears during clinical remission. As with earlier data, the findings point to platelet activity in AD increasing during flare, falling following therapy and normalizing upon remission.”
“This study evaluated secondary caries and periodontal conditions associated with metal (MCs) and composite resin copings (RCs) of abutment teeth for overdentures. The rates of secondary caries and periodontal problems in 70 root copings (41 MCs, 29 RCs) in 35 patients were retrospectively investigated for a period of 6.9 years.

A large body of evidence from both human and animal studies now p

A large body of evidence from both human and animal studies now points to a relationship between circadian disorders and altered metabolic response, suggesting that circadian and metabolic regulatory networks are tightly connected. After a review of the current understanding of the molecular circadian core clock, we will discuss the hypothesis that clock genes themselves

link the core molecular clock and metabolic regulatory NVP-BSK805 inhibitor networks. We propose that the nuclear receptor and core clock component Rev-erb-alpha behaves as a gatekeeper to timely coordinate the circadian metabolic response.”
“Trypanosomes are parasites that cycle between the insect host (procyclic form) and mammalian host (bloodstream form). These parasites lack conventional transcription regulation, including factors that induce the unfolded protein response (UPR). However, they possess a stress response mechanism, the spliced leader RNA silencing (SLS) pathway. SLS elicits shutoff of spliced leader RNA (SL RNA) transcription by perturbing the binding of the transcription factor tSNAP42 to its cognate promoter, thus eliminating trans-splicing of all mRNAs. Induction of endoplasmic reticulum (ER) stress in procyclic trypanosomes elicits changes in the transcriptome similar to those induced by conventional UPR found in other eukaryotes. The mechanism of

up-regulation under ER stress is dependent on differential stabilization of mRNAs. The transcriptome

changes are accompanied by ER dilation and elevation in the ER chaperone, BiP. selleck products Prolonged ER stress induces SLS pathway. RNAi silencing of SEC63, see more a factor that participates in protein translocation across the ER membrane, or SEC61, the translocation channel, also induces SLS. Silencing of these genes or prolonged ER stress led to programmed cell death (PCD), evident by exposure of phosphatidyl serine, DNA laddering, increase in reactive oxygen species (ROS) production, increase in cytoplasmic Ca(2+), and decrease in mitochondrial membrane potential, as well as typical morphological changes observed by transmission electron microscopy (TEM). ER stress response is also induced in the bloodstream form and if the stress persists it leads to SLS. We propose that prolonged ER stress induces SLS, which serves as a unique death pathway, replacing the conventional caspase-mediated PCD observed in higher eukaryotes.”
“Patient-reported outcomes are important for clinical practice and research, and should reflect what patients perceive as important. The objective of this study was to develop and preliminarily validate a brief, patient-derived, disease-specific tool, the pancreatic cancer disease impact (PACADI) score.\n\nThe development was performed in two phases. Forty-one patients with confirmed pancreatic cancer (PC) selected dimensions of health related to the impact of the disease.

Conclusion Test compounds exhibiting antiproliferative activ

\n\nConclusion. Test compounds exhibiting antiproliferative activity showed interesting results, which would promote their use as lead compounds on further studies for anticancer agents development.”
“Peste

des petits ruminants is a viral disease of sheep and goats that has spread through most of Africa as well as the Middle East and the Indian subcontinent. Although, the spread of the disease and its economic impact has made it a focus of international concern, relatively little is known about the nature of the disease itself. We have studied the early stages of pathogenesis in goats infected IPI-549 with six different isolates of Peste des petits ruminants virus representing all four known lineages of the virus. No lineage-specific difference in the pathogenicity of the virus isolates was observed, although there was evidence that even small numbers of cell culture passages could affect the degree of pathogenicity of

an isolate. A consistent reduction in CD4(+) T cells was observed at 4 days post infection (dpi). Measurement of the expression of various cytokines showed elements of a classic inflammatory response but also a relatively early induction of interleukin 10, which may be contributing to the observed disease.”
“A recombinant thermostable lipase (Pf2001 Delta 60) from the hyperthermophilic Archaeon Pyrococcus furiosus (PFUL) was immobilized by hydrophobic interaction SN-38 clinical trial on octyl-agarose (octyl PFUL) and by covalent bond on aldehyde activated-agarose in the presence of DTT at pH = 7.0 (one-point covalent attachment) (glyoxyl-DTT PFUL) and on glyoxyl-agarose at pH 10.2 (multipoint covalent attachment) (glyoxyl PFUL). The enzyme’s properties, such as optimal temperature and pH, thermostability, and selectivity, were improved by covalent immobilization. The highest enzyme stability at 70 degrees C for 48 h incubation was achieved for glyoxyl PFUL (around 82% of residual activity), whereas glyoxyl-DTT PFUL maintained around 69% activity, followed by octyl PFUL (27% remaining activity). Immobilization on glyoxyl-agarose improved the optimal temperature to 90 degrees C, while the

optimal temperature of octyl PFUL was 70 degrees C. Also, very significant selleck compound changes in activity with different substrates were found. In general, the covalent bond derivatives were more active than octyl PFUL. The E value also depended substantially on the derivative and the conditions used. It was observed that the reaction of glyoxyl-DTT PFUL using methyl mandelate as a substrate at pH 7 presented the best results for enantioselectivity (E = 22) and enantiomeric excess (ee (%) = 91).”
“Some birds in noisy areas produce songs with higher frequency and/or amplitude and altered timing compared to individuals in quiet areas. These changes may function to increase the efficacy of acoustic signals by reducing masking by noise. We collected audio recordings of red-winged blackbirds and measured noise levels.

The onset of contralateral gamma band synchronization following i

The onset of contralateral gamma band synchronization following imperative Go cues is positively correlated with reaction time. Remarkably, baseline levels of gamma activity shortly before the Go cue correlated with the reaction times. Here, faster responses occurred in patients with higher levels 4EGI-1 Others inhibitor of pre-cue gamma activity. Our findings support the role of gamma activity as a physiological prokinetic activity in the motor system. Moreover, we suggest that subtle fluctuations in pre-cue gamma band activity may have an impact on task performance and may index arousal-related states. (C) 2013 Elsevier Inc. All rights reserved.”
“Background:

Because few data are available on this topic, we investigated the influence of geographical determinants on colorectal adenoma detection and cancer incidence Torin 2 supplier rates.\n\nMethods: Between 1990 and 1999, 6220 Cote d’Or inhabitants (France) were first-diagnosed with a colorectal adenoma, and 2389 with an invasive adenocarcinoma. The impact of the rural-urban place of residence and of a physician location in municipalities on adenoma and cancer detection rates was studied using Poisson regression.\n\nResults: World-standardized adenoma detection rate was significantly higher in urban areas (102

[95%CI: 97-107]) than in rural areas (78 [95%CI: 72-84]). The impact of the absence of physicians in municipalities was only found in rural areas. The detection rate ratio associated with the absence www.selleckchem.com/products/idasanutlin-rg-7388.html of a primary care physician was 0.70 [95%CI:0.61-0.81], and the detection rate ratio associated with the absence of a gastroenterologist was 0.75 [95%CI:0.64-0.89]. Colorectal cancer incidence rates were similar in urban and rural areas with only marginal variations related to physician location.\n\nConclusions: These results suggested a differential impact of geographical variables on the detection rates of colorectal adenomas and cancers in the population. Further studies are needed to examine socioeconomic

factors likely to be involved in these disparities. (C) 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.”
“Background\n\nManagement of acute sore throat is often based on features associated with GABHS, but the features that best predict GABHS require clarification. Non-group A streptococcal strains share major similarities with group A strains, but their clinical presentation and incidence has not been clarified.\n\nObjective\n\nThe aim of this study was to assess the incidence and clinical features associated with streptococcal infections.\n\nDesign\n\nThis study comprised a prospective diagnostic cohort.\n\nSetting\n\nThe setting was UK primary care.

001) However, TH increased phase singularity number (wavebreaks)

001). However, TH increased phase singularity number (wavebreaks) during VF (P<0.05) and Si pacing (P<0.05). TH resulted in earlier onset of APD alternans (P<0.001), which was predominantly SDA (P<0.05), and increased pacing-induced VF episodes (P<0.05). TH also decreased CV, shortened wavelength, and enhanced APD dispersion and the spatial heterogeneity of CV restitution.\n\nConclusions: TH (30 degrees C) increased the vulnerability of pacing-induced VF by (1) facilitating wavebreaks during VF and Si pacing, and (2) enhancing proarrhythmic electrophysiological parameters, including promoting

earlier onset of APD alternans (predominantly SDA) during HER2 inhibitor S1 pacing. (Circ J 2009; 73: 2214-2222)”
“Brain metastasis has become an increasing cause of

morbidity G418 and mortality in cancer patients as the treatment of systemic disease has improved. Brain metastases frequently are highly vascularized, a process driven primarily by VEGF. VEGF mediates numerous changes within the vasculature including endothelial cell retraction and increased permeability, vasodilation, and new vessel formation. Here we describe a xenograft brain metastasis model that mimics the critical steps of metastasis including tumor cell dissemination and vascular adhesion, tumor growth and tumor associated angiogenesis. Magnetic resonance (MR) imaging was used to evaluate two aspects of the functional response of brain metastasis to the anti-VEGF receptor therapeutic, AZD2171 (Cediranib, RECENTIN (TM)). MR tracking of individual cells demonstrated that cediranib did not impede tumor

cell extravasation into the brain parenchyma despite evidence that anti-VEGF treatment decreases the permeability of the blood brain barrier. In a second assay, blood volume imaging using ultrasmall superparamagnetic iron oxide revealed that treatment of well-developed brain metastasis with cediranib for 7 days led to a heterogeneous response with respect to individual tumors. Overall, there was a significant average decrease in the tumor vascular bed volume. The majority of large tumors demonstrated substantially reduced central blood volumes relative to normal brain while retaining a rim of elevated blood volume at ACY-738 supplier the tumor brain interface. Small tumors or occasional large tumors displayed a static response. Models and assays such as those described here will be important for designing mechanism-based approaches to the use of anti-angiogenesis therapies for the treatment of brain metastasis.”
“Objective: We describe the short-term results of the patients who underwent transapical treatment of a paravalvular leak (PVL) in our centre. Background: Increasing experience with transapical aortic valve implantation has inspired us to explore this approach for prosthetic paravalvular leak reduction in high risk patients.

Hyponatremia and the syndrome of inappropriate antidiuretic hormo

Hyponatremia and the syndrome of inappropriate antidiuretic hormone secretion became the “attribute” disorders of nephrologists. Invention of a microflame photometer fostered the revival of micropuncture and transport studies. In the 1960s,

the flame photometer was linked to Leonard Skeggs’ sequential automated analysis system, leading to enormous numbers of routine measurements of electrolytes. The growing number of nephrologists, then based mostly at teaching hospitals, thus found plentiful instances of sodium and potassium find more abnormalities to address. The autoanalyzer also catalyzed use of the anion gap, another emblem of nephrology in its early decades. Not only ideas and theories, but also the usually invisible machinery, enable the growth of a knowledge base and formation of a scientific discipline or medical specialty. Of course, the flame photometer did not itself shape the agenda of nephrology, but it allowed the most influential group of progenitors and their progeny to explore normal function and bring a strongly physiologic imperative to their daily work with patients. Am J Kidney Dis 56:379-386. (C) 2010 by the National Kidney Foundation, Inc.”
“Lima

bean is a species cultivated broadly in the Americas and has been cultivated Selleck LY3023414 in the Caribbean for at least 500 years. In order to determine the genetic structure and 17-AAG clinical trial diversity of Lima bean from the Caribbean, 50 landraces from Haiti, the Dominican Republic and Puerto Rico were collected and analyzed using 24 SSR

markers. All landraces in this Caribbean collection were found to be of Middle-American descent. The genetic diversity (H-E) was highest in the landraces from Puerto Rico and lowest in Haitian landraces. The observed proportion of heterozygotes (H-O) was higher in the Haitian landraces and lowest in Puerto Rican landraces. Unweighted pair-group method with arithmetic averaging analysis showed that the landraces clustered into 3 clusters with all Haitian landraces grouping in one cluster. We also assessed the agro-morphological characteristics of the collection as well as the content of cyanogenic glucoside, linamarin, in leaves and dry seeds. Lima bean, which is a model crop for indirect plant defenses against herbivory, also possess linamarin as a source of direct plant defense. Upon tissue damage, linamarin is converted to toxic hydrogen cyanide. In our collection 44.6 % of the landraces had average seed HCN content <= 200 ppm which is the permitted level for Lima bean seed in the US. Our results also identified the landraces in this collection which have high linamarin levels in the leaves while having low levels in the seeds.

At approximately 24 wk of age, the wether lambs were slaughtered

At approximately 24 wk of age, the wether lambs were slaughtered to determine carcass characteristics and muscle samples were taken from the bicep femoris. The abundance of mature myostatin protein in

muscle from 1 wk old lambs was less (P = 0.05) in MSTN A/A and MSTN A/G compared with MSTN G/G lambs. However, at 4 and 24 wk the MSTN A/A lambs had a greater (P = 0.04) abundance of myostatin protein compared with the MSTN A/G and MSTN G/G lambs. The abundance of mature myostatin did not differ between genotypes in plasma but the myostatin protein did increase as the lambs aged. At slaughter the MSTN A/A wether lambs had greater dressing percentages (P = 0.04), shortloin (P = 0.01), topside (P < 0.001), and round (P = 0.01) weights but did not differ in final BW or HCW (P > 0.05). The

MSTN selleck chemicals A/A lambs had more muscle fibers (P = 0.02) in the cross-section of LM between the 12th and 13th rib. The MSTN A/A lambs also had greater lean (P = 0.002), less fat (P = 0.009), and reduced organ (heart, liver, spleen, and kidneys) mass as determined by computed tomography scanning than MSTN G/G lambs. selleck compound The results of this study demonstrated that lambs homozygous for the MSTN g+6723G > A mutation have changes in carcass characteristics (dressing and total lean), organ weights, and muscle fiber number. This may be due to reduced myostatin protein early in utero, but after 4 wk of age there was no difference in the abundance of mature myostatin protein in muscle or plasma among MSTN A/A, MSTN A/G, and MSTN G/G genotypes. (C) 2013 American Society of Animal Science. All rights reserved.”
“Off-policy reinforcement learning is aimed at efficiently using data samples gathered from a policy that is different from the currently optimized policy. A common approach is to use importance sampling techniques for compensating for the bias of value function estimators caused by the difference between the data-sampling policy and the target policy. However, existing off-policy methods

often do not take the variance of the value function estimators explicitly into account and therefore their performance tends Autophagy inhibitor manufacturer to be unstable. To cope with this problem, we propose using an adaptive importance sampling technique which allows us to actively control the trade-off between bias and variance. We further provide a method for optimally determining the trade-off parameter based on a variant of cross-validation. We demonstrate the usefulness of the proposed approach through simulations. (C) 2009 Elsevier Ltd. All rights reserved.”
“Objective To compare the length of hospitalisation for infants with bronchiolitis across the Eastern region and to assess the impact of the varying admission rates in each hospital.

All rights reserved “
“P>Aim This paper is a report o

All rights reserved.”
“P>Aim.\n\nThis paper is a report of a study conducted to describe primary healthcare personnel’s knowledge of multidrug-resistant and preventive hygiene measures.\n\nBackground.\n\nThe group of patients at risk for multi-drug resistant bacteria is largely cared for in primary care. Knowledge of multidrug-resistant

and hygiene preventive measures among primary healthcare personnel is therefore essential.\n\nMethod.\n\nA descriptive and comparative questionnaire survey among primary healthcare personnel was performed in 2008. In total, five urban and rural primary healthcare centres situated in one county in central Sweden were included. Convenient sampling was used and 10 physicians, 38 district nurses and 10 nursing assistants participated. Knowledge/medical facts concerning multidrug-resistant and hygiene preventive measures were investigated and data were analysed using a quantitative approach.\n\nResults.\n\nKnowledge/medical SCH 900776 purchase Selleckchem STI571 facts concerning several aspects of multidrug-resistant bacteria, particularly Extended-Spectrum-Beta-Lactamase producing bacteria, were deficient as was knowledge of different aspects of hygiene preventive measures. Physicians showed significantly better results than district nurses and nursing assistants did. Awareness of proper hand-washing as an effective preventive method and

use of aprons in nursing care was high among all participants. Staff who knew they had cared for these patients had significantly better results than the others did.\n\nConclusion.\n\nOur findings suggest that evidence-based education of multidrug-resistant and hygiene preventive measures, in primary health with subsequent follow-ups should become a prioritized Bucladesine research buy clinician and management concern. Research is needed that focus implementation of evidence-based educations, staff attitudes and responsibilities related to the work with patients at risk of multidrug-resistant

bacteria.”
“ZnO nanostructures (ZnO-NSs) of different morphologies are synthesized with the amino acids L-alanine, L-threonine, and L-glutamine as capping agents. X-ray diffraction (XRD) shows the formation of a crystalline wurtzite phase of ZnO-NSs. The surface modification of ZnO-NSs due to the capping agents is confirmed using Fourier transform infrared (FTIR) spectroscopy. Photoluminescence spectroscopy reveals that the concentration of surface defects correlates positively with the number of polar facets in ZnO-NSs. The antimicrobial activity of the ZnO-NSs has been tested against Escherichia coil and the common pathogens Staphylococcus aureus, Klebsiella pneumoniae, and Bacillus subtilis. Culture-based methods in rich medium show up to 90% growth inhibition, depending on the ZnO-NSs. Flow cytometry analyses indicate that the reactive oxygen species (ROS) generated by ZnO-NSs contribute mostly to the antibacterial activity.