The authors describe the most direct trajectory to the ventricular trigone using this approach and propose a point of entry that transects the cingulate gyrus at a point 5 mm superior and 5 mm posterior to the falco-tentorial junction.”
“Extinction, a form of learning that has the ability to reshape learned behavior based on new experiences, has been heavily studied

utilizing fear learning paradigms. Mechanisms underlying extinction of positive-valence associations, such as drug self-administration and place preference, are poorly understood yet may have important relevance to addiction treatment. Data suggest a major role for the noradrenergic system in extinction of fear-based learning. Employing both pharmacological and genetic approaches, we investigated buy Lonafarnib the role of the alpha(2)-adrenergic receptor (alpha(2)-AR) in extinction of cocaine-conditioned Enzalutamide datasheet place preference (CPP) and glutamatergic transmission in the bed nucleus of the stria terminalis (BNST). We found

that pre-extinction systemic treatment with the alpha(2)-AR antagonist yohimbine impaired cocaine CPP extinction in C57BL/6J mice, an effect that was not mimicked by the more selective alpha(2)-AR antagonist, atipamezole. Moreover, alpha(2)A-AR knockout mice exhibited similar cocaine CPP extinction and exacerbated extinction impairing effects of yohimbine. Using acute brain slices and electrophysiological approaches, we found that yohimbine produces a slowly evolving depression of glutamatergic transmission in the BNST that was

not mimicked by atipamezole. Further, this action was extant in slices from alpha(2)A-AR knockout mice. Our data strongly suggest that extinction-modifying effects of yohimbine are unlikely to be due to actions at alpha(2)A-ARs.”
“OBJECTIVE: PD184352 (CI-1040) Surgical approaches to the orbit require great precision and care because of the functional and aesthetic importance of this region. Conventional approaches to the posterior orbit often require bone removal, may disrupt extraocular muscles, and may create external surgical scars. We conceived a transconjunctival surgical approach to the medial intraconal space that is aided by a minimally invasive endoscopic technique and avoids muscle transection.

METHODS: Assisted by a rigid endoscope measuring 2.7 mm in diameter, with 0- and 30-degree lenses, we made a medial conjunctival incision along the limbus to approach the medial intraconal space and optic nerve in 7 fresh cadaver heads (a total of 9 procedures).

RESULTS: This approach provided direct and quick access to the medial intraconal space and intraorbital optic nerve with the use of endoscopes via an aesthetically acceptable conjunctival incision, and it provided an excellent view of the operative area. Unlike conventional techniques, this approach left the anatomy relatively undisturbed and did not require detachment of the medial rectus muscle.

OBJECTIVE: To examine whether side-to-side nerve bridges between an intact donor nerve and a recipient selleck denervated distal nerve stump promote nerve growth and in turn, protect distal nerve stumps to improve axon regeneration after delayed surgical repair.

METHODS: In Sprague-Dawley rats, 1 or 3 side-to-side common peroneal (CP) nerve bridges were used to bridge between the donor intact tibial (TIB) nerve and a recipient denervated CP distal nerve stump in the contralateral hind limb. No bridges were placed in control animals. After

4 months, either a fluorescent retrograde dye was applied to back-label TIB motoneurons with axons that had grown into the CP nerve stump or the proximal and distal CP nerve stumps were resutured in experimental and control animals to encourage CP nerve regeneration for 5 months. Retrograde dyes were again applied to count CP motoneurons that regenerated their axons through protected and unprotected nerve stumps.

RESULTS: Significantly more donor TIB motoneurons regenerated axons into the recipient denervated CP nerve stump through

3 side-to-side CP nerve bridges compared with 1 bridge. This TIB nerve protection significantly increased the number of CP motoneurons regenerating axons through the denervated CP nerve stumps, the number of regenerated axons, and the weight of the reinnervated muscles.

CONCLUSION: Multiple side-to-side nerve bridges protect chronically denervated nerve stumps to improve axon regeneration and target reinnervation after delayed nerve repair.”
“BACKGROUND: https://www.selleckchem.com/products/apo866-fk866.html Aneurysmal subarachnoid hemorrhage, almost

always from saccular intracranial aneurysm (sIA), is a devastating form of stroke that affects the working-age population. Cellular and molecular mechanisms predisposing to the rupture of the sIA wall are largely unknown. This knowledge would facilitate the design of novel diagnostic tools and therapies for the sIA disease.

OBJECTIVE: To investigate gene expression patterns distinguishing ruptured and unruptured sIA.

METHODS: We compared the whole-genome expression profile of 11 ruptured old sIA wall samples with that of 8 unruptured ones using oligonucleotide microarrays. Signaling pathways enriched in the ruptured sIA walls were identified with bioinformatic analyses. Their transcriptional control was predicted in silico by seeking the enrichment of conserved transcription factor binding sites in the promoter regions of differentially expressed genes.

RESULTS: Overall, 686 genes were significantly upregulated and 740 were downregulated in the ruptured sIA walls. Significantly upregulated biological processes included response to turbulent blood flow, chemotaxis, leukocyte migration, oxidative stress, vascular remodeling; and extracellular matrix degradation.

“
“To the Editor: According to classical writers, Celts were tall people; Caesar wrote that Celts looked with contempt on the short Romans (Commentarii de Bello Gallico, Book II, Chapter 30). The genetic mutation determining iron overload in HFE-associated hereditary hemochromatosis arose in Celtic populations in approximately 4000 B.C.(1) Iron is important for development, and iron deficiency has serious consequences for learning https://www.selleckchem.com/products/GSK1904529A.html ability and growth.(2) In turn, the growth rate affects iron status,

and iron demand tends to exceed supply in periods of rapid growth.(3) We therefore hypothesized that sustained enhanced iron absorption in patients with HFE hemochromatosis might have a beneficial effect on growth. We assessed

height in a cohort of 176 patients with HFE hemochromatosis at the University Hospital Zurich ( Switzerland). Homozygous C282Y mutations were found in 93% of patients, whereas a compound H63D- C282Y mutation was found in 7%. All patients had verified iron overload, defined as a serum ferritin level of more than 300 mu g per liter or a transferrin saturation of more than 45%. Height in patients with hemochromatosis was compared with that in an ageand sex- matched Swiss reference population, with the use of data reported in the registry of military conscription and by the Swiss Federal Statistical Lazertinib ic50 Office ( Fig. 1). Men with hemochromatosis ( 120 patients) were 4.3 cm taller, on average,than those in the reference population ( 458,322 persons) ( 95% confidence interval [ CI], 3.0 to 5.5; P< 0.001). The height was 178.2 cm in men with hemochromatosis, versus 173.9

cm in controls. The difference in height between women with hemochromatosis ( 56 patients) and those in the reference population ( 10,260 persons) was 3.3 cm ( 95% CI, 1.3 to 5.3; P< 0.001). The height was 167.1 cm in women with hemochromatosis versus 163.8 cm in controls. To avoid a bias related to an increased proportion of patients of Northern European origin in our hemochromatosis cohort, the data were validated with a reference population from Ireland, the country with the highest prevalence of the C282Y mutation in Europe. The deviation in height from the reference population remained stable over time and did not correlate with MycoClean Mycoplasma Removal Kit the type of HFE mutation, body- mass index, serum ferritin level, liver enzyme elevation, liver fibrosis, or clinical manifestations such as arthropathy or hypogonadism. The fundamental nonhematologic role of iron on metabolism has been shown in experimental models4 and in clinical studies5 ( see the Supplementary Appendix, available with the full text of this letter at NEJM. org). On the basis of our clinical observations, we speculate that patients with HFE hemochromatosis may benefit in their first two decades from constantly enhanced iron absorption, providing a steadily sufficient supply of iron during physical development.

The dDG-lesioned rats were normal, however, in discriminating

four different objects presented (Experiment 2) in c-Kit inhibitor the same locations as in Experiment 1. Finally, when the two different objects used in Experiment 1 were presented at two remote locations (Experiment 3) involving less overlap between arm-associated contextual cues, the dDG-lesioned animals showed initial deficits in discriminating the objects, but gradually relearned the task, in contrast to the sustained deficits observed in Experiment 1. These results collectively suggest that the DG is necessary when the similarity is maximal between object-place paired associates due to overlapping object and/or spatial information, whereas its role becomes minimal as the overlap in either object or spatial information decreases.”
“Long-term memory for fear of an environment (contextual CCI-779 in vitro fear conditioning) emerges later in development (postnatal day; PD 23) than

long-term memory for fear of discrete stimuli (PD 17). As contextual, but not explicit cue, fear conditioning relies on the hippocampus; this has been interpreted as evidence that the hippocampus is not fully developed until PD 23. Alternatively, the hippocampus may be functional prior to PD 23, but unable to cooperate with the amygdala for fearful learning. The current experiments investigate this by separating the phases of conditioning across developmental stages. Rats were allowed to learn about the context on one day and to form the fearful association on another. Rats exposed to the context on PD 17 exhibited significant fear only when trained and tested a week later (PD 23, 24), but not on consecutive days (PD 18, 19), demonstrating that rats can learn about a context as early as PD 17. Further experiments clarify that it is associative mechanisms that are developing between PD 18 Vasopressin Receptor and 23. Finally, the hippocampus was lesioned prior to training to ensure the task is being solved in a hippocampus-dependent manner. These data provide

compelling evidence that the hippocampus is functional for contextual learning as early as PD 17, however, its connection to the amygdala or other relevant brain structures may not yet be fully developed.”
“Electrolytic lesions of the medial prefrontal cortex (PFCX) were examined using fear conditioning to assess the recall of fear extinction and performance in the Y-maze, open field, and object location/recognition in male and female Sprague-Dawley rats. Rats were conditioned to seven tone/footshocks, followed by extinction after 1-h and 24-h delays, revealing PFCX effects and sex differences during all phases of fear conditioning. In male rats, PFCX impaired 24-h recall of fear extinction to tone, which required the 1-h delay extinction and was not attributed to nonassociative factors. In contrast, sham and PFCX females increased freezing to tone following a 24-h delay, whether or not 1-h delay tone extinction was presented.

No marked adverse effects in renal function were observed in animals treated with MEL alone or CA alone, but evidence related to nephrotoxicity was noted in rats administered MC. Renal calculi and increased kidney weights were found in rats 7 d after daily oral administration of MC. Blood urea nitrogen (BUN) and creatinine were significantly elevated in the high dose MC groups at 100x or 1000x. In addition, elevated numbers of white blood cells (WBC), neutrophils, and lymphocytes in vivo and increased levels of prostaglandin E2 (PGE2) in vitro were found in the MC group. Based on these data, the NOAEL (no-observed-adverse-effect AZD1480 mw level)

for nephrotoxicity for MC was estimated to be 3.15 mg/kg body weight (bw)/d (MEL) plus 2.5 mg/kg bw/d (CA). If a safety factor of 1000 or more were applied to NOAEL, tolerable daily intake (TDI) would be 0.00315 and 0.0025 mg/kg/d or less for MEL and CA, respectively, which is far below the TDI

of 0.2 mg/kg/d set by World Health Organization (WHO). In addition, in vitro cytotoxicity assays showed that the ACHN human renal adenocarcinoma cell line was more sensitive to MEL, CA, and MC than the MDCK canine kidney epithelial cell line. The 24-h half maximal inhibitory concentration (IC50) values for MEL (4792, 2792 g/ml) were less than those of CA (9890, 6725 g/ml, respectively) in MDCK and PKA activator ACHN cell lines, suggesting that MEL may be more cytotoxic than CA. Furthermore, the 24-h IC50 value for MC was found to be 208 g/ml in ACHN cells. Data suggest that NOAELs based upon acute

nephrotoxic parameters for MC were low, which might require further reassessment of the current TDI.”
“In the brain, the stress system plays an important role in motivating continued alcohol use and relapse. The neuropeptide substance P and the neurokinin-1 receptor (NK1R) are involved in the stress response and drug reward systems. Recent findings have shown that the binding of ligands to NK1Rs decreases the self-administration of alcohol in mice. We examined the effect of an artificial microRNA (amiRNA) on the functional expression of NK1R in mouse brains. Lentiviruses expressing either an amiRNA PLEKHM2 targeting the NK1R (amiNK1R) or a negative control amiRNA (amiNC) were injected into mouse brains. Four weeks after amiRNA injection, we found that amiNK1R decreased the voluntary alcohol consumption compared to mice injected with amiNC. We also observed that NK1R expression was reduced in the hippocampus. RNA interference is an effective approach to regulate the expression of specific behavior-related genes. Our results support the potential use of amiRNA as a therapeutic agent for the treatment of alcohol dependence. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Toxicometabolomics of urinary biomarkers for human gastric cancer in a mouse model was investigated using 1H-nuclear magnetic resonance (NMR) spectroscopy.

Copyright (C) 2008 S. Karger AG, Basel.”
“The entry of human cytomegalovirus (HCMV) into biologically relevant epithelial and endothelial cells involves endocytosis GSK1838705A purchase followed by low-pH-dependent fusion. This entry pathway is facilitated by the HCMV UL128, UL130, and UL131 proteins, which form one or more complexes with the virion envelope glycoprotein gH/gL. gH/gL/UL128-131 complexes appear to be distinct from the gH/gL/gO complex, which likely facilitates entry into fibroblasts. In order to better understand the assembly and protein-protein interactions of

gH/gL/UL128-131 complexes, we generated HCW mutants lacking UL128-131 proteins and nonreplicating adenovirus vectors expressing gH, gL, UL128, UL130, and UL131. Our results demonstrate that UL128, UL130, and UL131 can each independently assemble onto gH/gL scaffolds. However, the binding of individual UL128-131 proteins onto gH/gL can significantly affect the binding of other proteins; for example, UL128 increased the binding of both UL130 and UL131 to gH/gL. Direct interactions between gH/UL130, UL130/UL131, gL/UL128, and UL128/UL130 were also observed. The export of gH/gL complexes from the endoplasmic

reticulum (ER) to the Golgi apparatus and cell surface was dramatically increased when all of UL128, UL130, and UL131 were coexpressed with gH/gL (with or without gO expression). Incorporation of gH/gL complexes into the virion envelope requires transport beyond the ER. Thus, we concluded that UL128, UL130, and UL131 must CCI-779 purchase all bind simultaneously onto gH/gL for the production of complexes that can function in entry into epithelial and endothelial cells.”
“The pathogenesis of anorexia nervosa (AN) is still poorly understood. The Diagnostic and Statistical Manual of Mental Disorders (4th edition) classification differentiates 2 AN types: the restricting type (AN-R) and the binge eating/purging type (AN-BP). We investigated 4 young women suffering from AN (2 with AN-R and 2 with AN-BP). Four women, age matched, with other psychiatric disorders (paranoid

schizophrenia, adjustment disorder, mental retardation) served as the reference group. The oligonucleotide microarray method (HG-U133A, Affymetrix) was used to determine the expression profile of 13 genes connected with the orexigenic G protein-coupled receptor kinase and anorexigenic system: leptin, leptin receptor-coding gene, hypocretin (orexin) receptor-coding gene, hypocretin (orexin) neuropeptide precursor-coding gene and growth hormone secretagogue receptor. A hierarchical analysis of the results showed that AN-BP and AN-R patients were grouped into different clusters. Also, expression levels of leptin receptor-coding gene showed significant differences between AN-BP and AN-R patients and between AN-R and control subjects. This preliminary study suggests that the microarray technique may contribute to elucidating molecular genetics of the pathogenesis of both types of AN. Copyright (C) 2008 S. Karger AG, Basel.

c.) just prior to each

drug administration), corticosterone (20%, s.c., pellet), or both. Mice were subjected to a cocaine sensitization regimen (15.0 mg/kg cocaine on nine consecutive days followed by a 7.5 mg/kg cocaine challenge after a 5-day withdrawal).

In agreement with our previous observations, ADX prevented initiation and expression of cocaine-induced locomotor sensitization. Whereas neither corticosterone nor epinephrine alone were sufficient to reverse the ADX effect, both hormones were necessary to fully restore initiation and retention Selleckchem AZD0156 of sensitization to levels observed in SHAM animals.

The present findings indicate that corticosterone and epinephrine cooperate to facilitate behavioral responsiveness to cocaine. These data emphasize that in addition to the hypothalamic-pituitary-adrenal axis, the sympathetic nervous system plays a critical role in psychostimulant sensitivity.”
“The Drosophila melanogaster gustatory system consists

of several neuronal pathways representing diverse taste modalities. The two predominant modalities are a sweet-sensing pathway that mediates attraction, and a bitter-sensing pathway that mediates avoidance. A central question is how flies integrate Baf-A1 mw stimuli from these pathways and generate the appropriate behavioral response. We have developed a novel assay for induction of taste memories. We demonstrate Progesterone that the gustatory response to fructose is suppressed when followed by the presence of bitter quinine. We employ optogenetic neural activation using infrared laser in combination with heat-sensitive channel – TRPA1 to precisely activate gustatory neurons. This optogenetic system allows for spatially and temporally controlled activation of distinct neural classes in the gustatory circuit. We directly activated bitter-sensing neurons together with presentation of fructose for remote induction of aversive taste memories. Here we report that activation of bitter-sensing neurons in the proboscis suffices as a conditioning stimulus. Spatially restricted stimulation indicates that the conditioning stimulus

is indeed a signal from the bitter neurons in the proboscis and it is independent of postingestive feedback. The coincidence of temporally specific activation of bitter-sensing neurons with fructose presentation is crucial for memory formation, establishing aversive taste learning in Drosophila as associative learning. Taken together, this optogenetic system provides a powerful new tool for interrogation of the central brain circuits that mediate memory formation. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.”
“C-reactive protein (CRP), an acute phase protein that is released in response to inflammatory stimuli, is implicated in Alzheimer’s disease (AD). However, the role of CRP in memory deficits associated with AD remains unclear.

The outcome was self-reported awareness of the prostate specific antigen test. The main independent

variables were smoking status, physical activity level, body mass index and alcohol consumption. The prevalence, OR and 95% CI for prostate specific antigen awareness were calculated using SUDAAN (R) to account for the complex sampling design.

Results: The overall prevalence of prostate specific antigen awareness was 73.0%. After controlling for potential confounders the odds of being aware learn more of the prostate specific antigen test was lower in current smokers (vs never smoked OR 0.53, 95% CI 0.41-0.68), physically inactive men (vs physically active OR 0.77, 95% CI 0.63-0.93) and obese men (vs normal weight OR 0.77, 95% CI 0.62-0.95).

Conclusions: Health risk behaviors are associated with lower prostate specific antigen awareness. Our findings suggest opportunities for focused health education interventions and quality improvement programs tailored to men who,engage in unhealthy behaviors to improve their prostate specific HM781-36B antigen test awareness.”
“Clinical evidence indicates that motor

training facilitates functional recovery after a spinal cord injury (SCI). Brain-derived neurotrophic factor (BDNF) is a powerful synaptic facilitator and likely plays a key role in motor and sensory functions. Spinal cord hemisection decreases the levels of BDNF below the injury site, and exercise can counteract this decrease [Ying Z, Roy RR, Edgerton VR, Gomez-Pinilla F (2005) Exercise restores levels of neurotrophins and synaptic plasticity

following spinal cord injury. Exp Neurol 193:411-419]. It is not clear, however, whether the exercise-induced increases in BDNF play a role in mediating the recovery of locomotion after a SCI. We performed a lateral cervical (similar to C4) hemisection 4-Aminobutyrate aminotransferase in adult rats. Seven days after hemisection, the BDNF inhibitor trkB IgG was injected into the cervical spinal cord below the lesion (similar to C5-C6). Half of the rats were exposed to voluntary running wheels for 14 days. Locomotor ability was assessed by determining the symmetry between the contralateral (unaffected) vs. the ipsilateral (affected) forelimb at the most optimum treadmill speed for each rat. Sedentary and exercised rats with BDNF inhibition showed a higher level of asymmetry during the treadmill locomotion test than rats not treated with the BDNF inhibitor. In hemisected rats, exercise normalized the levels of molecules important for synaptic function, such as cyclic AMP response element binding protein (CREB) and synapsin 1, in the ipsilateral cervical enlargement, whereas the BDNF blocker lessened these exercise-associated effects.

Understanding the epidemiology

of PAD to improve its detection and treatment among Hispanics is relevant to reduce disparities in the health status of this group, the most rapidly growing ethnic minority in the United States. (J Vasc Surg 2010;51:27S-35S.)”
“Disparities in health care are well documented for several racial, ethnic, and gender groups. In peripheral arterial disease, differences in prevalence, treatment selection, treatment outcomes, and resulting quality of life have negative effects on some minority groups and women. It may be easy to document disparities, but it is harder to understand their underlying causes. Are there biologic differences between members of racial and ethnic groups that influence disease presentation and outcomes? Or is the socioeconomic environment that surrounds them learn more the true driver of observed differences? This article reviews the evidence for racial and

gender disparities in vascular surgery and presents some potential mechanisms that may explain the disparities. (J Vasc Surg 2010;51:36S-41S.)”
“Prior research has established diversity as a topic of empirical analysis in the vascular surgery literature. Building on the work of previously published articles on diversity in the Journal of Vascular Surgery and elsewhere, this article engages in a broad discussion of diversity in two interrelated arenas: educational/workplace diversity and culturally competent care. Interdisciplinary review of the literature indicates that diversity is often thought of as an end-state to be accomplished. A more fruitful way to encompass the Apoptosis inhibitor changing aspects of diversity work is to think of diversity as a set of processes that can be adjusted based on a set of interrelated goals that matter differently to different groups. In considering diversity as a process, an approach to diversity emerges that considers both oxyclozanide independent

effects of gender and race/ethnicity as well as interactive effects between the two variables to address future trends in medical education. Such trends are diagnosed and multiple courses of intervention are offered as reasonable options for future efforts. A comprehensive definition of diversity will be established in order to encompass two different arenas in which diversity concerns arise: educational diversity and culturally competent patient care. Second, a discussion of the rationales for attention to diversity among vascular surgeons will provide different avenues into a conversation about diversity in the profession. In so doing, three successful efforts will be briefly discussed: the Ohio State University’s MED-Path program, the Keck School of Medicine’s chair-centered approach to diversity in residency training, and the American Association of Orthopedic Surgeons’ (AAOS) approach to culturally competent care. (J Vasc Surg 2010;51:42S-46S.

Data were collected during daytime fMRI sessions with simultaneous EEG acquisition. A stage-1 interval was defined as follows: >= 30 s of wake, immediately followed by >= 60 s of continuous stage 1, immediately followed by >= 30 s of stage 2. We compared brain activity between the first 30 s of stage 1 (early stage 1), the last 30 s of stage 1 (late stage 1), and isolated wake. A conjunction analysis sorted each voxel into one of a series of mutually exclusive categories that represented the various

possible combinations of a significant increase, decrease, or no difference among these three states. The initial dataset consisted of 14 healthy volunteers. A total of 22 sessions in these participants yielded six Dibutyryl-cAMP purchase stage-1 selleck compound intervals (from four participants) that met criteria for inclusion in the analysis. There were multiple clusters of significant voxels. Examples include changes in default-mode network areas where activity increased compared to wake only in early stage 1 and a bilateral change in the hippocampus where activity increased compared to wake only in late stage 1. These results suggest that activity in anatomically identifiable, volumetric brain regions exhibit differences during stage-1 sleep that would not have been detected with the EEG. These differences may also have specific relevance to understanding the process of sleep onset as well as the neural mechanisms of performance lapses during sleep deprivation.

Published by Elsevier Ireland Ltd.”
“Background The risk of venous thromboembolism is high after total hip arthroplasty and could persist after hospital discharge. Our aim was to compare the use of rivaroxaban for extended thromboprophylaxis with short-term thromboprophylaxis with enoxaparin.

Methods 2509 patients scheduled to undergo elective total hip arthroplasty were randomly assigned,

stratified according to Centre, with a computer-generated randomisation code, to receive,oral rivaroxaban 10 mg once daily for 31-39 days (with placebo injection for 10-14 days; n=1252), or enoxaparin 40 mg once daily subcutaneously for 10-14 days (with placebo tablet for 31-39 days; n=1257). The primary efficacy outcome was the composite of deep-vein thrombosis (symptomatic or asymptornatic detected by mandatory, Alanine-glyoxylate transaminase bilateral venography), non-fatal pulmonary embolism, and all-cause mortality up to day 30-42. Analyses were done in the modified intention-to-treat population, which consisted of all patients who had received at least one dose of study medication, had undergone planned surgery, and had adequate assessment of thromboembolism. This study is registered at ClinicalTrials.gov, number NCT00332020.

Findings The modified intention-to-treat population for the analysis of the primary efficacy outcome consisted of 864 patients in the rivaroxaban group and 869 in the enoxaparin group. The primary outcome occurred in 17 (2 . 0%) patients in the rivaroxaban group, compared with 81 (9.