Such strategies require accurate and comprehensive measurement of balance ability. The Berg Balance Scale was developed in 1989 using health professional and patient interviews, which explored the various methods used to assess balance.4 Thirty-eight component balance tests were originally selected and then refined through further interviews and trials to 14 items, each scored from 0 to 4, making a possible total score between 0 and 56, with a higher score indicating better balance. Although the Berg Balance Scale was originally developed to measure balance in the elderly, it has since been

used to measure balance in a wide variety of patients. The convergent validity of the Berg Balance Scale has find more been established across several different domains. Hospital inpatients with a lower Berg balance

score have been found to have a significantly higher chance of being discharged to nursing home accommodation.5 Among community-dwelling veterans, progressively lower Berg Balance Scale scores are associated with increased risk of injurious falls.3 Responsiveness to change was established in a trial enrolling sedentary older people, where those who exercised improved their Berg Balance Scale scores and reported fewer falls, compared to a control group.6 The Berg Balance Scale also had greater ability than four other performance measures to predict the onset of difficulty in activities of daily living in older adults.7 Normative data are important when interpreting any balance tool, both for

clinicians and researchers. Knowledge that a person or a group of people has significantly worse balance than a healthy person Selleck Y 27632 of the same age may assist the identification and effective management of balance problems. The effect of interventions to improve balance can be assessed by comparison to normative data for balance from healthy elderly people in specific age cohorts. Knowledge of the variability of the Berg Balance Scale in groups of healthy elderly people can be used to interpret individual results and to help establish the sample sizes required for future studies. An earlier review8 searched for the phrase ‘Berg Balance Scale’ and, despite finding 511 articles, did not identify any published review of normative data of the Berg Balance Scale. The study questions for the systematic review were: 1. What is the mean Berg Balance Scale score of healthy Adenosine elderly people living in the community and how does it vary with age? A literature search was undertaken to locate all relevant published studies. Electronic searches of MEDLINE, CINAHL, Embase, and the Cochrane Library databases from 1980 to September 2012 were conducted using ‘Berg Balance Scale’ as the search term. No keywords related to intervention type or health condition were used and no methodological filters to identify particular study designs were used. All potentially relevant papers were identified by screening the abstracts and assessed for inclusion.

Screening of all clinical isolates was done according to CLSI method.16 A-1210477 in vitro The detection of carbapenemase production was performed

by phenotypic test using imipenem-EDTA disc method as described earlier.17 The test organism was inoculated onto Mueller–Hinton agar (MHA, Himedia, Mumbai, India) and an increase of 7 mm or more in zone diameter in the presence of EDTA compared to imipenem tested alone was considered to be a positive test for the presence of a carbapenemase. All of the isolates phenotypically positive for carbapenemase were checked for carbapenemase genotypically by PCR. PCR analysis for metallo β-lactamase genes was carried out using the previously reported methods.18 and 19 The sequence of oligonucleotide primers has been shown in Table 1. All of the primers were procured from Sigma Aldrich Chemicals Private Limited, Bangalore, India. For PCR amplifications, about 200 pg of DNA was added to 20 μl mixture containing 0.5 mM of dNTPs, 1.25 μM of each primer and 3.0 U of Taq polymerase (Bangalore Genei) in 1X

PCR buffer. Amplification was performed in an Eppendorf thermal cycler (Germany). The amplified products were separated in 1.5% agarose gel containing 4 μl of 10 mg/ml of ethidium bromide. The gel was run at 70 V for 1 h. The gel images were taken under ultraviolet light using gel documentation system (Bio-Rad, USA). A 100 bp BKM120 ladder molecular weight marker (Bangalore Genie) was used to measure the molecular weights of amplified products. DNA isolation from the clinical isolates was conducted using the alkaline lysis method.20 The antimicrobial susceptibility testing of the drugs were determined by the disc diffusion method according to the Clinical Laboratory Standards MTMR9 Institute method (CLSI).16 Quality controls (QC) were performed on each day of testing using Pseudomonas aeruginosa ATCC 27853, Stenotrophomonas maltophilia ATCC 13636 as the reference strain throughout study. All of the clinical isolates obtained from various clinical specimens

were identified as A. baumannii based on their morphological and biochemical characterization. Out of the 454 clinical isolates of A. baumannii, 371 (81.71%) were found to be carbapenemase producing. The maximum carbapenemase producers were found in urine specimen 87.27% (144/165) followed by blood 84.55% (115/136), respiratory secretion 80% (12/15), pus 73.40% (69/94), and fluid 70.45% (31/44). Genotypic screening of carbapenemase producing isolates revealed that 86.5% (321/371) isolates were carbapenemase positive via PCR method (Table 2 and Table 3). Table 4 shows the prevalence of carbapenemase in different clinical specimens of A. baumannii isolates. The highest percentage of carbapenemase producers were confirmed genotypically in isolates obtained from urine 95.1% (137/144) followed by respiratory secretion 91.6% (11/12), blood 82.6% (95/115), pus 79.

Similar arguments can be made for the MCC vaccines, which have achieved virtual eradication of serogroup C meningococcal disease in a number of countries where it has been introduced [46]. It should be noted here

that it is more accurate to say that serogroup C ST-11 complex meningococci, which express their capsules at high rates, have been eradicated [37]. It is possible that other genotypes which express the capsule at lower rates, and are consequently less susceptible MCC vaccines, could act as a reservoir for the genes encoding the serogroup C capsule, making its eradication difficult. Trametinib ic50 A further problem is that meningococci that express this capsule are globally distributed [16], including in countries that have low incidence rates of disease, which might be resistant to the universal introduction of a vaccine against an organism Androgen Receptor antagonist which represents only a modest threat to their public health – evidence for this is the patchy introduction of this vaccine in European counties. Those countries which have immunised children and young adults with MCC vaccines, such as the United Kingdom and the Netherlands, have exhibited the most dramatic reductions in serogroup C disease [36] and [47]. Compared with Phase I, Phase II presents a number of uncertainties. Serogroups W and, particularly, Y are less common causes of disease and are commonly carried. In addition they are found in a range

ALOX15 of clonal complexes, a number of which very rarely cause disease and their rates of capsule expression during carriage are lower, ranging from 28 to 70%, depending on the clonal complex [29] and [48]. Experience from the UK MCC introduction suggests that it was the high rate of capsule expression in carriage, combined with genetic uniformity of the ST-11 complex serogroup C meningococci, which resulted in the high impact of the vaccine [37]. Extrapolating this success to other serogroups, especially Y and W may well be optimistic. More worryingly, the apparently very low invasive potential of serogroup Y ST-22 complex meningococci [29], suggests

that their elimination may be detrimental to disease control, at least whilst other more invasive meningococci are still circulating. Very high rates of serogroup Y carriage have been reported and, whilst these have been associated with increases in rates of serogroup Y disease, these remain very low compared with the disease rates that occur during periods of elevated transmission of hyperinvasive serogroup B and C meningococci [29]. It is at least possible the serogroup Y organisms prevent disease by excluding more harmful organisms and attempting their elimination must take this into account. Further, the low levels of capsule expression of some clonal complexes associated with serogroup Y during carriage [48] may render their elimination impossible with current approaches.

Le groupe de travail chargé de l’actualisation des « Standards Options Recommandations » de 2002 [8], [9] and [10], a récemment publié une mise à jour concernant le fentanyl transmuqueux d’action rapide [11] and [12]. La prochaine actualisation portera sur « la rotation d’opioïdes » ou « changement d’opioïdes ». Face à une douleur cancéreuse, il est toujours recommandé d’associer des médicaments de mode d’action différent, notamment : • des antalgiques de paliers différents ; On dispose aujourd’hui d’un arsenal thérapeutique étendu de traitements antalgiques, et notamment d’opioïdes forts dont l’efficacité antalgique et le profil click here de tolérance sont see more globalement les mêmes

[14] and [15], hormis une moindre incidence de constipation avec le fentanyl transdermique [16](encadré 2). Palier I : antalgiques non opioïdes • Paracétamol – AINS – Acide acétylsalicylique Palier II : opioïdes faibles • Codéine associée au paracétamol : Efferalgan-Codéine®, Co-Doliprane®, Dafalgan-codéine®, Klipal Palier III : opioïdes forts Opioïdes forts agonistes purs (voir tableaux) • Morphine Face à une douleur nociceptive, si un antalgique de palier II à posologie optimale devient inefficace, on prescrira une molécule de palier III (morphine ou oxycodone)

et l’initiation comportera une phase de titration. Cependant, face à une douleur intense, un antalgique de palier III peut être prescrit d’emblée, sans passer par le palier II. Selon les recommandations de l’Association européenne de soins palliatifs (EAPC) de 2012 [17], on peut soulager une douleur cancéreuse légère à modérée, avec des opioïdes forts d’emblée, sans effets indésirables majeurs. Il est donc possible de les prescrire en première intention pour traiter une douleur cancéreuse nociceptive, others quelle que soit l’intensité douloureuse, en adaptant la posologie [18] and [19]. La période de titration

initiale consiste à déterminer les besoins du patient en opioïdes forts, c’est-à-dire à définir la posologie minimale qui permettra d’obtenir un soulagement satisfaisant du patient. Deux méthodes existent : soit l’administration à intervalles réguliers d’une dose fixe d’opioïde fort à libération prolongée (LP), s’il existe une douleur de fond, associée à des doses de secours ou interdoses d’opioïdes à libération immédiate (LI) en fonction des accès douloureux ; soit l’administration à la demande, en fonction de l’intensité des douleurs, d’opioïdes à LI seuls, au maximum six fois par jour (encadré 3). La titration permet une adaptation fine du traitement antalgique, qui conduit à une meilleure gestion de la douleur par le patient (autocontrôle), avec le minimum d’effets indésirables, du fait de l’utilisation de la dose juste nécessaire.

Startle responses can be measured in rodents using loud acoustic tones, and can be enhanced in fear-potentiated startle, a paradigm in which startle is tested in an environment previously paired with footshocks. Selleckchem SAHA HDAC Central administration of NPY inhibits both basal acoustic startle and fear-potentiated startle in rodents (Broqua and et al, 1995, Gilpin and et al, 2011 and Gutman and et al, 2008). Another study demonstrated that NPY infusion into the basolateral, but not central nucleus, of the amygdala mimics the effects of NPY on acoustic startle and fear-potentiated responses (Gutman

et al., 2008). Central administration of a Y1R agonist attenuates fear-potentiated startle, whereas a Y2R agonist was reported to have no effect (Broqua et al., 1995). In genetically Alisertib in vivo modified rodents, knockout of NPY or Y2R enhances acoustic startle (Bannon et al., 2000), whereas deletion of the Y1R yields impaired habituation of startle responses (Karl et al., 2010). These studies indicate a role for NPY in the modulation of startle and potential for NPY as a therapeutic for hyperarousal in stress-related psychiatric

disorders. However the receptor subtypes and brain regions dictating NPY-induced resilience to this behavioral response remain unclear. The NE system originating in the locus coeruleus (LC) is a brainstem region contributing to arousal responses (Samuels and Szabadi, 2008 and Sara and Bouret, 2012), thus NPY may mediate arousal behavior by directly acting in the LC or by influencing brain regions upstream. Fig. 1 demonstrates putative neurochemical interactions and circuitry that may influence the function of the LC-NE system and arousal behavior. NPY inhibits the firing rate of NE neurons in the LC, and potentiates the effect of NE on presynaptic autoinhibition

of neuronal firing (Illes et al., 1993 and Finta et al., 1992). This electrophysiological evidence suggests that NPY may act to restrain the activity of noradrenergic neurons, which may have important implications for stress-psychiatric diseases in which the LC-NE system is disrupted. In combination with anatomical evidence demonstrating rich NPY check innervation of the LC (Smialowska, 1988) (shown in Fig. 2),these studies suggest that NPY may play an important role in the regulation of noradrenergic stress responses and arousal via NE circuitry. Recent rodent studies suggest that NPY may be useful in the treatment of psychiatric diseases such as PTSD, which is heavily characterized by behavioral sequelae associated with fear. NPY has been found to influence multiple fear-related behaviors including the acquisition, incubation, expression, and extinction of conditioned fear. For example, i.c.v.

A modified bilateral transfrontal sinus approach [45] was made with an air-powered high-speed drill (Hall Micro 100 drill 5053-09, Zimmer-Hall, Warsaw, IN) and oscillating saw cooled by continuous lavage with isotonic saline solution. The dura was sharply incised and reflected to expose the right frontal lobe. Pial vessels were cauterized with bipolar electrocoagulation and the neoplastic tissue was excised using blunt and sharp dissection and suction Src inhibitor aspiration. Tumor samples were placed in culture media in preparation for isolation and culture of brain tumor cells for vaccine production

and in 10% formalin for processing for histopathology. Immediately following tumor debulking, 6.0 × 108 infectious units of Ad-IFNγ were administered into the resection cavity by 28 injections (2 μl/site, 1–2 cm deep) covering the circumference of the cavity. Ad-IFNγ, encoding human IFNγ regulated by the CMV promoter, was produced as previously described [46]. The dura was closed. Gelatin sponges (Gel Foam, Upjohn Co., Kalamazoo, mTOR kinase assay MI) were placed over the dura, and the bone flap was replaced. Then the subcutaneous tissues and skin were closed over the craniotomy. The dog recovered

from anesthesia in the intensive care unit and was monitored for seizure activity until discharged from the hospital. The dog received hydromorphone (0.05 μg/kg SC QID) for analgesia, methylprednisolone sodium succinate (15 mg/kg IV 12 h and 7.5 mg/kg IV 24 h after surgery), and phenobarbital (1.5 mg/kg IV BID) as an anticonvulsant in the ICU. After discharge, phenobarbital (1.5 mg/kg PO BID) mafosfamide was continued, a tapering dose of prednisolone (1 mg/kg PO BID × 3 days, 0.5 mg/kg PO BID × 3 days, 0.5 mg/kg PO EOD × 3 days), and morphine sulfate SR (1 mg/kg PO BID × 3 days) were administered. Autologous and allogeneic canine astrocytoma cells used for vaccination were grown in DMEM/F12 media supplemented with N2, B27 (Invitrogen,

Carlsbad, CA) and 20 ng/ml of human epidermal growth factor and basic fibroblast growth factor (Peprotech, Rocky Hill, NJ). The allogeneic cells were derived from a French bulldog. The tumors used to make cell cultures were dissociated as previously described [18]. Cells were cultured at 37 °C, 5% O2, 5% CO2 in a humidified incubator in 10 cm dishes or 75 cm2 flasks. All vaccinations were prepared as follows. Cells were harvested, washed thrice in PBS, and resuspended in 200 μl PBS. Lysates were generated by the freeze thaw method as previous described [14] and lysates were further irradiated at 200 Gy to ensure complete tumor cell death. Each vaccine administered consisted of an average of 536 μg of protein lysate (range 230–641 μg) mixed with 2 mg of phosphorothioated-unmethylated type-B CpG ODN 685 (5′-tcgtcgacgtcgttcgttctc-3′; SBI Biotech, Japan).

Dans des populations de patients alcoolodépendants, quatre essais randomisés contrôlés versus placebo, en double insu, ont été publiés [11], [18], [19], [20], [21] and [22]. Dasatinib datasheet Dans les groupes traités par topiramate, ils ont mis en évidence une diminution significative des

taux plasmatiques de CDT (transferrine déficiente en carbohydrate, marqueur biologique de la consommation d’alcool) [10], et une amélioration des échelles relatives à l’alcoolodépendance (Obsessive Compulsive Drinking Scale [OCDS], Drinker Inventory of Consequences [DrInC]) [20] and [21]. Trois de ces essais [18], [19], [20], [21] and [22] ont fait l’objet d’une méta-analyse [23], totalisant 635 patients. Celle-ci a retrouvé, dans le groupe traité par topiramate, une diminution de 23 % du nombre de jours de consommation massive (p < 0,001) et une augmentation significative du nombre de jours d’abstinence supplémentaires (+2,9 jours, p < 0,001). Un essai monocentrique randomisé, contrôlé versus placebo, en ouvert pendant quatre mois (n = 90) a retrouvé une augmentation significative de la durée moyenne d’abstinence dans le groupe traité par topiramate [10] ( tableau I). Le topiramate a été comparé à la naltrexone,

médicament utilisé dans l’aide au maintien de l’abstinence chez les patients alcoolodépendants, dans trois essais monocentriques randomisés. Un essai en double click here insu pendant 12 semaines

(n = 155, dont topiramate n = 52, naltrexone n = 49, placebo n = 54) n’a pas montré de différence significative concernant les consommations d’alcool (durée d’abstinence cumulée, pourcentage de semaines avec consommation massive) [22]. Un essai ouvert pendant six mois (n = 102) a retrouvé des taux significatifs d’abstinence dans Tryptophan synthase le groupe de patients traités par topiramate [24]. Un autre essai ouvert pendant six mois (n = 182) a observé un nombre de jours de consommation massive plus faible dans le groupe de patients traités par topiramate [9]. Un essai monocentrique randomisé contrôlé ouvert pendant neuf mois (n = 100) a retrouvé une durée moyenne d’abstinence significativement plus élevée chez les patients traités par disulfirame [25]. Un essai monocentrique randomisé contrôlé versus placebo, en double insu, pendant 11 semaines (n = 87) n’a pas montré de différence entre la mesure du monoxyde de carbone expiré dans le groupe de patients traités par topiramate et le groupe de ceux recevant le placebo [26]. L’efficacité du topiramate dans la dépendance au tabac a été évaluée dans des sous-groupes de patients alcoolodépendants inclus dans deux autres essais [27] and [28]. Les sujets recevant du topiramate avaient significativement plus de chance de s’abstenir de fumer par rapport à ceux sous placebo [28].

The experimental intervention was electrical stimulation (ten trials), position-triggered electrical stimulation (one trial), EMG-triggered electrical stimulation (three

trials), and a combination of EMG-triggered or position-triggered electrical stimulation and electrical stimulation (two trials). Ten trials delivered usual therapy to both experimental and control groups. Fourteen trials applied electrical stimulation to one or two muscles Luminespib research buy per limb with only two trials13 and 22 applying it to four different muscles. Measures of strength were mainly maximum voluntary force production, either continuous measures of force or torque (14 trials), or ordinal measures such as manual muscle tests (two trials). Most trials used direct measures of activity (five trials reported continuous data, and three trials reported ordinal data), and only one trial used an indirect measure. Seven trials did not measure activity. The overall effect of electrical stimulation on strength immediately after intervention was examined by pooling post-intervention data from 11 trials with a mean PEDro score of 5.1, representing moderate quality (Figure 2a, see Figure 3a on the eAddenda

for the detailed forest plot). Overall, the effect size was 0.47 find more (95% CI 0.26 to 0.68) in favour of electrical stimulation. Two trials,8 and 12 that were unable to be included in the pooled analysis, also reported significant between-group differences in strength in favour of electrical stimulation. Maintenance of the benefit was examined

by pooling post intervention data from five trials that measured below strength beyond the intervention period. Overall, the increase in strength was maintained with an effect size of 0.33 (95% CI 0.07 to 0.60) (Figure 2b, see Figure 3b on the eAddenda for the detailed forest plot). When the trials were grouped according to the initial level of strength, electrical stimulation increased the strength in very weak participants (eight trials) with an effect size of 0.40 (95% CI 0.17 to 0.65), and in weak participants (three trials) with an effect size of 0.66 (95% CI 0.21 to 1.11). When the trials were grouped according to the time after stroke, electrical stimulation increased the strength in sub-acute participants (six trials) with an effect size of 0.55 (95% CI 0.28 to 0.81), while in chronic participants (five trials) the effect size was 0.33 (95% CI −0.02 to 0.69). The overall effect of electrical stimulation on activity immediately after intervention was examined by pooling post intervention data from six trials with a mean PEDro score of 5.7 out of 10 (Figure 4a, see Figure 5a on the eAddenda for the detailed forest plot). Overall, electrical stimulation improved activity with an effect size of 0.30 (95% CI 0.05 to 0.56).

13 Each dried fraction was reconstituted in 100 μL of 0.1% formic acid and analyzed using a linear ion trap–Fourier transform (LTQ–FT) Ultra mass spectrometer (Thermo Electron,

Bremen, Germany) coupled with a ProminenceTM HPLC unit (Shimadzu, Kyoto, Japan). For each analysis, samples was injected from an autosampler (Shimadzu) and concentrated in Cobimetinib supplier a Zorbax peptide trap (Agilent, Palo Alto, CA). The peptide separation was performed in a capillary column (75 μm inner diameter × 15 cm) packed with C18 AQ (5 μm particles, 300 Å pore size; Michrom Bioresources, Auburn, CA). Mobile phase A (0.1% formic acid in H2O) and mobile phase B (0.1% formic acid in acetonitrile) were used to establish the 90 minute gradient comprising 3 minutes of 0-5% B and then 52 minutes of 5-25% B followed by 19 minutes of 25-80% B, maintenance at 80% B for 8 minutes, and finally reequilibration at 5% B for 8 minutes. The HPLC system was operated at a constant flow rate of 30 μL minute−1, and a splitter was used to create an effective flow rate of approximately 300 nL minute−1 at the

Nutlin-3a research buy electrospray emitter. The sample was injected into an LTQ-FT through an Advance CaptiveSpray source (Michrom Bioresources) with an electrospray potential of 1.5 kV. The gas flow was set at 2, ion transfer tube temperature was 180°C, and collision gas pressure was 0.85 millitorr. The LTQ-FT was set to perform data acquisition in the positive ion mode as described previously.13 Briefly, a full mass spectrometry (MS) scan (350–1600 m/z range) was acquired in the FT-ICR cell at a resolution of 100,000. The linear ion trap was used to collect peptides and to measure peptide fragments generated by CID. The 10 most intense ions above a 500-count threshold were selected for fragmentation in CID (MS2). For each experiment, MS/MS (dta) spectra of the 8 gel fractions were combined into a single mascot generic file by a home-written program. Protein

identification was achieved by searching unless the combined data against the international protein index human protein database (version 3.34; 69,164 sequences, 29,064,825 residues) via an inhouse Mascot server (version 2.3.02; Matrix Science, London, UK). The search parameters were: a maximum of 2 missed cleavages using trypsin; fixed modification was carbaminomethylation of cysteine, and variable modifications was oxidation of methionine. The mass tolerances were set to 10 ppm and 0.8 Da for peptide precursor and fragment ions respectively. Protein identification was accepted as true positive if 2 different peptides were found to have scores greater than the homology or identity scores. Statistical analysis was performed using Mann–Whitney U test. Differences were considered to be statistically significant when the P values were less than .05. Plasma was incubated with biotinylated CTB or AV followed by streptavidin-conjugated magnetic beads.

7 reported per million doses administered) was similar to that found in seasonal influenza vaccination and preliminary pandemic (H1N1) vaccination in the United States [33] (Table 2). Analyses in LAC have shown a baseline rate of 0.82 GBS cases

IWR-1 research buy per 100,000 children aged less than 15 years [34]. There were 72 cases of anaphylaxis that were classified as related to vaccination; rate of 0.5 per million doses. Twenty-seven seizures (both febrile and non-febrile) were reported; rate of 0.19 per million doses (Table 2). Risk communication was a key component throughout the planning and implementation of pandemic influenza (H1N1) vaccination campaigns. PAHO’s guidelines included risk communication strategies for countries to prepare for anticipated vaccine shortages and to focus their vaccination efforts on specific high risk groups [35] As the pandemic evolved and rumors related to vaccine safety emerged, risk communication again became critical to promote the importance

of pandemic influenza vaccine as a safe means to reduce morbidity and mortality among high risk groups. A group of experts in risk communication was convened to support selected countries in their social communication and crisis management activities (Bolivia, El Salvador, Guatemala, Paraguay, and Suriname). Countries faced challenges in the accurate estimation of some high risk groups to be vaccinated during campaigns. Many of the target populations for pandemic influenza (H1N1) vaccination were not traditionally targeted by immunization programs, such as individuals with chronic medical conditions. In many countries, systematic information for campaign AT13387 chemical structure planning was not available. Population estimates for people with chronic conditions also varied greatly across LAC, and denominators were generally underestimated, resulting in many countries reporting coverage well over 100%. Defining the order of priority of different about chronic health conditions was another challenge which will be important to consider during future pandemic

planning. Many countries initially made conservative estimates of health care workers and planned to vaccinate mainly first responders. However, during the implementation of vaccination campaigns, as more vaccine became available, additional health care workers were often vaccinated, resulting in some countries reporting coverage >100%, as original denominators were never adjusted. PAHO’s weekly reporting of the advances in national pandemic influenza (H1N1) vaccination and reported ESAVI served to monitor progress and disseminate information to interested parties. This information sharing was only achieved through diligent and voluntary country reporting. It would be necessary to formalize such regular reporting as a standard practice for the common good during future situations involving mass vaccination campaigns. The experience with pandemic influenza (H1N1) revealed the importance of including immunization as an integral part of pandemic planning.