text:
Background Postoperative respiratory problems, especially apnea, is a common postoperative complication in ex-preterm neonates undergoing infraumbilical operations. So, most of these neonates require close postoperative monitoring for at least 12 h to avoid this hazard. Postoperative apnea is related more to the use of respiratory depressant drugs used during general anesthesia.
Aim The aim was to evaluate safety and effectiveness of spinal anesthesia in ex-preterm infants undergoing infraumbilical operations and evaluate its role in elimination of routine postoperative hospital stay for apnea monitoring.
Settings and design A prospective single-blinded randomized study was conducted.
Materials and methods From March 2015 to March 2016, 105 ex-preterm neonates (gestational age <37 weeks), with postconceptual age at surgery less than 60 weeks, undergoing elective infraumbilical operations were studied prospectively. Patients were divided randomly into three groups (35 patients each). Group I received spinal anesthesia without sedation (only sugared pacifier), group II received spinal anesthesia with sedation in the form of ketamine/midazolam, and group III received general anesthesia with caudal analgesia. Postoperative apnea, bradycardia, and oxygen saturation were observed and compared for 12 h after operation. The primary outcome measures were postoperative apnea, postoperative bradycardia, and SpO2. The secondary outcome measures were postoperative complications (e.g. hypotension) and the need for postoperative respiratory support.
Results No patients in group I developed any attacks of postoperative apnea, postoperative bradycardia, or hypoxia. On the contrary, 11 patients in group II and 16 patients in group III developed attacks of postoperative apnea and hypoxia and required postoperative respiratory support.
Conclusion Spinal anesthesia without sedation is safe and effective for infraumbilical operations in ex-preterm neonates with short hospitalization.
Apnea of prematurity is a very common neonatal hazard, accounting for 25% of preterm and ex-preterm infants following recovery from general anesthesia. The distributions of postoperative apnea are either central (70%), obstructive (10%), or mixed (20%) .
High-risk infants for postoperative apnea are those who are born prematurely (<37 weeks), infants with multiple congenital anomalies, infants with a previous history of postoperative apnea and bradycardia, and those with chronic lung disease. Apneic spell is defined as a pause in breathing of more than 20 s or one of less than 20 s associated with bradycardia and/or cyanosis .
The incidence of apnea is related to the gestational as well as postconceptual age (PCA). An infant born at a lower gestational age is more likely to have apnea than one with same PCA but born later. This risk reduces with increase in duration of PCA up to 60 weeks PCA .
Apnea in premature infants is exacerbated by hypoxia, sepsis, intracranial hemorrhage, metabolic abnormalities, hypo/hyperthermia, upper airway obstruction, heart failure, anemia (hematocrit <30%), vasovagal reflexes, and drugs (including prostaglandins and anesthetic agents) .
Decreased ventilatory control and decreased response to hypoxia and hypercarbia may be increased by anesthetic agents. The highest incidence of significant apnea and bradycardia is in the first 4–6 h postoperatively, but it was reported to be up to 12 h after surgery. High-risk infants for development of postoperative apnea may benefit from a regional anesthetic as opposed to a general anesthetic .
Therefore, these infants require postoperative monitoring in high dependency unit for at least 12 h and should not be anesthetized as outpatients even if regional anesthesia has been administered. In fact, some authors suggest that wherever possible, anesthesia should be delayed until the ex-premature infant is older than 52 weeks PCA .
Our study was carried out in the Pediatric Surgery Department of Ain Shams University educational hospital in the period from March 2015 to March 2016. After approval of local ethical committee, 105 pediatric patients of both sexes, American Society of Anesthesiology I and II physical status, were included in our study. The age group included formerly preterm neonates with postconceptual age less than 60 weeks, undergoing elective infraumbilical surgery. Detailed informed patient consents were taken from parents. Preanesthetic evaluation was done to all pediatric patients included in the study.
Patients were excluded if they have known allergy to local anesthetics, coagulopathy, pre-existing cardiac, metabolic or neuromuscular diseases, uncontrolled convulsions, local infection at puncture site, or parent refusal.
Patients were randomly allocated by sealed envelopes using computer-generated table into three groups (35 patients each). In all groups, no premedications were given. Intravenous cannula was inserted and secured. No fluid preloading was given.
Group I (35 patients) included patients who received spinal anesthesia without sedation (only sugared pacifier was used). Group II (35 patients) included patients who received spinal anesthesia with sedation in the form of intravenous ketamine (1 mg/kg) plus intravenous midazolam 50 µg/kg. Sedation in group II was given after performing the subarachnoid block. Under aseptic condition, spinal anesthesia was performed through midline approach while the patient is in the sitting position and supported by an assistant. After local skin infiltration with 1% lidocaine, lumbar puncture was done in L4/L5 interspace using 25-G 25-mm pencil-point spinal needle. Hyperbaric bupivacaine 0.5% (0.5 mg/kg) was injected in the subarachnoid space after getting free flow of cerebrospinal fluid. Drug injection was done using 1-ml syringe, which was prepared and the correct dose was calculated before dural puncture. After injection, the infant was placed in the supine position. Successful spinal block was proved by sudden and complete loss of leg movement with normal tone in both arms indicating that sensory level was below C8. In groups I and II, oxygen was given through nasal cannula at a rate of 3 l/min. Neonates with failed spinal anesthesia were anesthetized with general endotracheal anesthesia and excluded from the study.
Group III (35 patients) included patients who received general anesthesia with 2 minimum alveolar concentration (MAC) sevoflurane in 100% oxygen and muscle relaxation with atracurium (induction dose 0.5 mg/kg and maintenance dose 0.1 mg/kg). After insertion of a correctly sized endotracheal tube, caudal analgesia was done using 0.25% bupivacaine 0.5 ml/kg. Neuromuscular block was antagonized at the end of surgery with atropine and neostigmine under guidance of neuromuscular monitoring.
Routine intraoperative monitoring was applied to all patients [i.e. ECG, pulse oximetry, noninvasive blood pressure (BP), and temperature monitoring]. Warming blankets were used to minimize heat loss in all infants.
Intraoperative sedation level in groups I and II was assessed, every 5 min till end of surgery, using sedation/agitation scale (SAS) ([Table 1]) . During the operation, the infant in group I was comforted by the anesthesiologist to prevent excessive upper limb movement, with the help of a sugared pacifier.
On completion of operations, and after fulfilling criteria of recovery from general anesthesia in group III, all patients were transferred to intermediate care unit, warming blankets was used, and nasal oxygen was applied at a rate of 3 l/min. Continuous monitoring were done for 12 h postoperatively. Monitoring was done by bedside monitor which measures SpO2. Respiratory rate and heart rate (HR) were measured through ECG leads connected to patients’ chest. The monitor alarm was adjusted to sound when respiration ceases for more than 20 s (i.e. apnea) or if the HR decreases less than 100 beats/min (i.e. bradycardia) for more than 20 s or SpO2 decreases to less than 90%. Noninvasive BP was monitored, and evidence of hypotension (i.e. >20% decrease in systolic BP from baseline) was treated with 10 ml/kg intravenous crystalloid.
These data (i.e. HR, respiratory rate, SpO2, and mean BP) were recorded every hour up to 12 h postoperatively. The number and timing of apnea, bradycardia, and hypotensive attacks were recorded and compared in the three groups. The observer who monitored the patients was blind to the type of anesthetic technique and group allocation.
Infants developing attacks of apnea or bradycardia in the postoperative period were managed with tactile stimulation; if there was no response, bag and O2 mask ventilation together with airway positioning and suctioning were done. Persistent bradycardia despite previous measures was treated with intravenous atropine 0.01 mg/kg. Infants who developed apnea attack were kept on O2 therapy in the intermediate care unit for further 12 h.
The primary outcome measures were postoperative apnea, postoperative bradycardia, and postoperative SpO2. The secondary outcome measures were postoperative complications (e.g. hypotension), the need for postoperative respiratory support, and SAS score.
A sample size of 98 achieves 80% power to detect a 15% difference in incidence between the three groups with an effect size (W) of 0.3500. χ2-Test with a significance level (α) of 0.05 was used. A total of 35 patients per group were included to replace any dropouts.
Data were analyzed using SPSS 17 for Windows (SPSS; SPSS Inc., Chicago, Illinois, USA). Analysis of variance was used to compare the three groups for quantitative parametric data with post-hoc Tukey’s test performed if there was a significant difference among the groups. χ2-Test was used for comparison of qualitative data. Continuous parametric data were presented as mean±SD, categorical data were presented as number and percentage of patients, and nonparametric data were compared using Mann–Whitney test and were expressed as median (interquartile range). P values of less than 0.05 were considered significant.
A total of 105 patients were enrolled in our study. There was no statistically significant difference among the three groups regarding demographic data, duration of anesthesia, and duration of surgery (P>0.05) ([Table 2]).
[Table 3] shows a comparison among the three groups regarding postoperative apnea, postoperative bradycardia, oxygen saturation, respiratory support, and hypotension. Regarding apneic spells, we noticed that no patients in group I had experienced postoperative apneic spills. On the contrary, 11 (31.4%) patients in group II and 16 (45.7%) patients in group III had experienced postoperative apnea (P<0.001).
Postoperative apnea time was 3.49±1.56 and 3.97±1.68 h in group II and III, respectively. In group II, eight patients developed one attack of apnea, two patients developed two attacks, and one patient developed three attacks. In group III, 10 patients developed one attack of apnea, four patients developed two attacks, and two patients developed three attacks ([Table 4]).
The same finding was noticed for postoperative bradycardia; no patients in group I had experienced postoperative bradycardia. On the contrary, 11 (31.4%) patients in group II and 16 (45.7%) patients in group III had experienced postoperative bradycardia (P<0.001).
Mean intraoperative and postoperative oxygen saturation was always high in group I as compared with the other two groups. No patients in group I needed respiratory support. On the contrary, 11 patients in group II and 16 patients in group III needed respiratory support. Respiratory support ranged from tactile stimulation to bag and mask ventilation. None of these apneic episodes required intubation and ventilation.
Two patients in group I, two patients in group II, and three patients in group III experienced hypotension, and the difference was nonsignificant (P>0.05) ([Table 3]).
No significant difference was observed among the three group regarding mean intraoperative and postoperative temperature (P=0.52).
Intraoperative sedation levels were compared between group I and group II according to SAS. Patients in group II were at deeper sedation level than patients in group I throughout the operation. At 5 min after spinal anesthesia, SAS was 5 (4–5) in group I compared with 1 (1–1) in group II. At 30 min after spinal anesthesia, SAS was 4 (3–4) in group I compared with 2 (2–3) in group II (P<0.001) ([Table 5]).
Neonatal spinal anesthesia, especially in ex-premature neonates, is gaining popularity and become a common practice in some pediatric surgery departments. The advantages are the avoidance of respiratory depressant drugs used during general anesthesia and eliminating the need for postoperative respiratory support.
In our study, we examined the effect of spinal anesthesia alone without any sedation on the incidence of postoperative apnea. Only sugared pacifier was used to sedate the infants. We detected that no patients in this group experienced any attacks of postoperative apnea or bradycardia, and no one needed any postoperative respiratory support. On the contrary, patients who received spinal anesthesia with intravenous sedation (midazolam plus ketamine) and those who received general anesthesia experienced attacks of postoperative apnea and bradycardia (11 patients in group II and 16 patients in group III).
Multiple previous studies have demonstrated that preterm infants have a higher incidence of respiratory problems than full-term infants. The risk of apnea in preterm infants undergoing inguinal herniorrhaphy increased to 37% following general anesthesia compared with 89% rate for spinal anesthesia with ketamine sedation and 0% apnea rate with spinal anesthesia alone .
Many factors are implicated in the development of apneic spell in ex-preterm neonates. These factors include diaphragmatic fatigue, diminished central respiratory drive, hypothermia, anemia, airway obstruction, residual effect of inhaled anesthetic, and muscle relaxant ,.
A study done by Wellborn et al.  compared spinal and general anesthesia in former premature infants. The study showed that spinal anesthesia without ketamine sedation was not accompanied with postoperative apnea, whereas neonates receiving general anesthesia or spinal anesthesia with intramuscular ketamine sedation (1–2 mg/kg before placement of the spinal anesthetic) developed 31 and 89% postoperative apnea, respectively .
In infants, metabolic rate of midazolam is lower than in adults. Midazolam elimination is approximately 4–6 h in neonates and up to 22 h in premature infants. Half-life of midazolam is 3.3-fold longer and clearance is 3.7-fold smaller than in adults .
A study done by Frumiento et al.  in 2000 concluded that awake spinal anesthesia, without sedation, reduced the incidence of postoperative apnea and need for respiratory support. It has been documented in the literature that subarachnoid anesthesia itself has a sedating effect. A study done by Hermanns et al.  evaluated sedation during spinal anesthesia in infants. One of the possible mechanisms for sedation is decreased afferent conduction to the reticulothalamocortical pathways and hence reduced excitability and arousal to the brain .
In a small randomized trial, Williams et al.  compared spinal anesthesia and general anesthesia with sevoflurane on postoperative recovery after inguinal herniotomy in ex-premature infants. They concluded that apnea and bradycardia occurred three times more frequent in the sevoflurane group .
A limitation to our study was that we did not include the preoperative hematocrit level as a risk factor for development of postoperative apnea. Anemia (i.e. hematocrit <30%) seemed as an important risk factor predisposing to postoperative apnea. Another limiting factor was the short duration of spinal anesthesia in neonates and thus not suitable for long-duration operations.
Subarachnoid block without sedation (only sugared pacifier) is an excellent choice for ex-preterm neonates with PCA less than 60 weeks undergoing infraumbilical operations allowing calm patients without significant agitation.
Kurth CD, LeBard SE. Association of postoperative apnoea, airway obstruction, and hypoxemia in former premature infants. Anaesthesiology 1991; 75:22–26.
Bayley G. Special considerations in the premature and ex-premature infant. Anesth Int Care 2010; 12:91–94.
Henderson-Smart DJ. The effect of gestational age on the incidence and duration of recurrent apnoea in new-born babies. Aust Paediatr J 1981; 17:273–276.
Pillekamp F, Hermann C, Keller T, von Gontard A, Kribs A, Roth B. Factors influencing apnoea and bradycardia of prematurity − implications for neurodevelopment. Neonatology 2007; 91:155–161.
Cote CJ, Zaslavsky A, Downes JJ, Kurth CD, Welborn LG, Warner LO et al. Postoperative apnoea in former preterm infants after inguinal herniorrhaphy. A combined analysis. Anaesthesiology 1995; 82:809–822.
Steer PA, Henderson-Smart DJ. Caffeine versus theophylline for apnoea in preterm infants. Cochrane Database Syst Rev 2010; 1:CD000273.
Welborn LG, Rice LJ, Hannallah RS, Broadman LM, Ruttimann UE, Fink R. Postoperative apnea in former preterm infants: prospective comparison of spinal and general anaesthesia. Anaesthesiology 1990; 72:838–842.
Silins V, Julien F, Brasher C, Nivoche Y, Mantz J, Dahmani S. Predictive factors of PACU stay after herniorraphy in infant: a classification and regression tree analysis. Paediatr Anaesth 2012; 22:230–238.
Sale SM, Read JA, Stoddart PA, Wolf AR. Prospective comparison of sevoflurane and desflurane in formerly premature infants undergoing inguinal herniotomy. Br J Anaesth 2006; 96:774–778.
Welborn LG, Rice LJ, Hannallah RS, Brodman LM, Ruttimann UE, Fink R. Postoperative apnoea in former premature infants: prospective comparison of spinal and general anaesthesia. Anaesthesiology 1990; 72:838–842.
Young TE, Neofax MB. A manual of drugs used in neonatal care. 23rd ed. Montvale, NJ, USA: Thomson Reuters; 2010.
Frumiento C, Abajian JC, Vane DW. Spinal anaesthesia for preterm infants undergoing inguinal hernia repair. Arch Surg 2000; 135:445–451.
Hermanns H, Stevens MF, Werdehausen R, Braun S, Lipfert P, Jetzek-Zader M. Sedation during spinal anaesthesia in infants. Br J Anaesth 2006; 97:380–384.
Williams JM, Stoddart PA, Williams SA, Wolf AR. Post-operative recovery after inguinal herniotomy in ex-premature infants: comparison between sevoflurane and spinal anaesthetic. Br J Anaesth 2001; 86:366–371.

lowercased:
background postoperative respiratory problems, especially apnea, is a common postoperative complication in ex-preterm neonates undergoing infraumbilical operations. so, most of these neonates require close postoperative monitoring for at least 12 h to avoid this hazard. postoperative apnea is related more to the use of respiratory depressant drugs used during general anesthesia.
aim the aim was to evaluate safety and effectiveness of spinal anesthesia in ex-preterm infants undergoing infraumbilical operations and evaluate its role in elimination of routine postoperative hospital stay for apnea monitoring.
settings and design a prospective single-blinded randomized study was conducted.
materials and methods from march 2015 to march 2016, 105 ex-preterm neonates (gestational age <37 weeks), with postconceptual age at surgery less than 60 weeks, undergoing elective infraumbilical operations were studied prospectively. patients were divided randomly into three groups (35 patients each). group i received spinal anesthesia without sedation (only sugared pacifier), group ii received spinal anesthesia with sedation in the form of ketamine/midazolam, and group iii received general anesthesia with caudal analgesia. postoperative apnea, bradycardia, and oxygen saturation were observed and compared for 12 h after operation. the primary outcome measures were postoperative apnea, postoperative bradycardia, and spo2. the secondary outcome measures were postoperative complications (e.g. hypotension) and the need for postoperative respiratory support.
results no patients in group i developed any attacks of postoperative apnea, postoperative bradycardia, or hypoxia. on the contrary, 11 patients in group ii and 16 patients in group iii developed attacks of postoperative apnea and hypoxia and required postoperative respiratory support.
conclusion spinal anesthesia without sedation is safe and effective for infraumbilical operations in ex-preterm neonates with short hospitalization.
apnea of prematurity is a very common neonatal hazard, accounting for 25% of preterm and ex-preterm infants following recovery from general anesthesia. the distributions of postoperative apnea are either central (70%), obstructive (10%), or mixed (20%) .
high-risk infants for postoperative apnea are those who are born prematurely (<37 weeks), infants with multiple congenital anomalies, infants with a previous history of postoperative apnea and bradycardia, and those with chronic lung disease. apneic spell is defined as a pause in breathing of more than 20 s or one of less than 20 s associated with bradycardia and/or cyanosis .
the incidence of apnea is related to the gestational as well as postconceptual age (pca). an infant born at a lower gestational age is more likely to have apnea than one with same pca but born later. this risk reduces with increase in duration of pca up to 60 weeks pca .
apnea in premature infants is exacerbated by hypoxia, sepsis, intracranial hemorrhage, metabolic abnormalities, hypo/hyperthermia, upper airway obstruction, heart failure, anemia (hematocrit <30%), vasovagal reflexes, and drugs (including prostaglandins and anesthetic agents) .
decreased ventilatory control and decreased response to hypoxia and hypercarbia may be increased by anesthetic agents. the highest incidence of significant apnea and bradycardia is in the first 4–6 h postoperatively, but it was reported to be up to 12 h after surgery. high-risk infants for development of postoperative apnea may benefit from a regional anesthetic as opposed to a general anesthetic .
therefore, these infants require postoperative monitoring in high dependency unit for at least 12 h and should not be anesthetized as outpatients even if regional anesthesia has been administered. in fact, some authors suggest that wherever possible, anesthesia should be delayed until the ex-premature infant is older than 52 weeks pca .
our study was carried out in the pediatric surgery department of ain shams university educational hospital in the period from march 2015 to march 2016. after approval of local ethical committee, 105 pediatric patients of both sexes, american society of anesthesiology i and ii physical status, were included in our study. the age group included formerly preterm neonates with postconceptual age less than 60 weeks, undergoing elective infraumbilical surgery. detailed informed patient consents were taken from parents. preanesthetic evaluation was done to all pediatric patients included in the study.
patients were excluded if they have known allergy to local anesthetics, coagulopathy, pre-existing cardiac, metabolic or neuromuscular diseases, uncontrolled convulsions, local infection at puncture site, or parent refusal.
patients were randomly allocated by sealed envelopes using computer-generated table into three groups (35 patients each). in all groups, no premedications were given. intravenous cannula was inserted and secured. no fluid preloading was given.
group i (35 patients) included patients who received spinal anesthesia without sedation (only sugared pacifier was used). group ii (35 patients) included patients who received spinal anesthesia with sedation in the form of intravenous ketamine (1 mg/kg) plus intravenous midazolam 50 µg/kg. sedation in group ii was given after performing the subarachnoid block. under aseptic condition, spinal anesthesia was performed through midline approach while the patient is in the sitting position and supported by an assistant. after local skin infiltration with 1% lidocaine, lumbar puncture was done in l4/l5 interspace using 25-g 25-mm pencil-point spinal needle. hyperbaric bupivacaine 0.5% (0.5 mg/kg) was injected in the subarachnoid space after getting free flow of cerebrospinal fluid. drug injection was done using 1-ml syringe, which was prepared and the correct dose was calculated before dural puncture. after injection, the infant was placed in the supine position. successful spinal block was proved by sudden and complete loss of leg movement with normal tone in both arms indicating that sensory level was below c8. in groups i and ii, oxygen was given through nasal cannula at a rate of 3 l/min. neonates with failed spinal anesthesia were anesthetized with general endotracheal anesthesia and excluded from the study.
group iii (35 patients) included patients who received general anesthesia with 2 minimum alveolar concentration (mac) sevoflurane in 100% oxygen and muscle relaxation with atracurium (induction dose 0.5 mg/kg and maintenance dose 0.1 mg/kg). after insertion of a correctly sized endotracheal tube, caudal analgesia was done using 0.25% bupivacaine 0.5 ml/kg. neuromuscular block was antagonized at the end of surgery with atropine and neostigmine under guidance of neuromuscular monitoring.
routine intraoperative monitoring was applied to all patients [i.e. ecg, pulse oximetry, noninvasive blood pressure (bp), and temperature monitoring]. warming blankets were used to minimize heat loss in all infants.
intraoperative sedation level in groups i and ii was assessed, every 5 min till end of surgery, using sedation/agitation scale (sas) ([table 1]) . during the operation, the infant in group i was comforted by the anesthesiologist to prevent excessive upper limb movement, with the help of a sugared pacifier.
on completion of operations, and after fulfilling criteria of recovery from general anesthesia in group iii, all patients were transferred to intermediate care unit, warming blankets was used, and nasal oxygen was applied at a rate of 3 l/min. continuous monitoring were done for 12 h postoperatively. monitoring was done by bedside monitor which measures spo2. respiratory rate and heart rate (hr) were measured through ecg leads connected to patients’ chest. the monitor alarm was adjusted to sound when respiration ceases for more than 20 s (i.e. apnea) or if the hr decreases less than 100 beats/min (i.e. bradycardia) for more than 20 s or spo2 decreases to less than 90%. noninvasive bp was monitored, and evidence of hypotension (i.e. >20% decrease in systolic bp from baseline) was treated with 10 ml/kg intravenous crystalloid.
these data (i.e. hr, respiratory rate, spo2, and mean bp) were recorded every hour up to 12 h postoperatively. the number and timing of apnea, bradycardia, and hypotensive attacks were recorded and compared in the three groups. the observer who monitored the patients was blind to the type of anesthetic technique and group allocation.
infants developing attacks of apnea or bradycardia in the postoperative period were managed with tactile stimulation; if there was no response, bag and o2 mask ventilation together with airway positioning and suctioning were done. persistent bradycardia despite previous measures was treated with intravenous atropine 0.01 mg/kg. infants who developed apnea attack were kept on o2 therapy in the intermediate care unit for further 12 h.
the primary outcome measures were postoperative apnea, postoperative bradycardia, and postoperative spo2. the secondary outcome measures were postoperative complications (e.g. hypotension), the need for postoperative respiratory support, and sas score.
a sample size of 98 achieves 80% power to detect a 15% difference in incidence between the three groups with an effect size (w) of 0.3500. χ2-test with a significance level (α) of 0.05 was used. a total of 35 patients per group were included to replace any dropouts.
data were analyzed using spss 17 for windows (spss; spss inc., chicago, illinois, usa). analysis of variance was used to compare the three groups for quantitative parametric data with post-hoc tukey’s test performed if there was a significant difference among the groups. χ2-test was used for comparison of qualitative data. continuous parametric data were presented as mean±sd, categorical data were presented as number and percentage of patients, and nonparametric data were compared using mann–whitney test and were expressed as median (interquartile range). p values of less than 0.05 were considered significant.
a total of 105 patients were enrolled in our study. there was no statistically significant difference among the three groups regarding demographic data, duration of anesthesia, and duration of surgery (p>0.05) ([table 2]).
[table 3] shows a comparison among the three groups regarding postoperative apnea, postoperative bradycardia, oxygen saturation, respiratory support, and hypotension. regarding apneic spells, we noticed that no patients in group i had experienced postoperative apneic spills. on the contrary, 11 (31.4%) patients in group ii and 16 (45.7%) patients in group iii had experienced postoperative apnea (p<0.001).
postoperative apnea time was 3.49±1.56 and 3.97±1.68 h in group ii and iii, respectively. in group ii, eight patients developed one attack of apnea, two patients developed two attacks, and one patient developed three attacks. in group iii, 10 patients developed one attack of apnea, four patients developed two attacks, and two patients developed three attacks ([table 4]).
the same finding was noticed for postoperative bradycardia; no patients in group i had experienced postoperative bradycardia. on the contrary, 11 (31.4%) patients in group ii and 16 (45.7%) patients in group iii had experienced postoperative bradycardia (p<0.001).
mean intraoperative and postoperative oxygen saturation was always high in group i as compared with the other two groups. no patients in group i needed respiratory support. on the contrary, 11 patients in group ii and 16 patients in group iii needed respiratory support. respiratory support ranged from tactile stimulation to bag and mask ventilation. none of these apneic episodes required intubation and ventilation.
two patients in group i, two patients in group ii, and three patients in group iii experienced hypotension, and the difference was nonsignificant (p>0.05) ([table 3]).
no significant difference was observed among the three group regarding mean intraoperative and postoperative temperature (p=0.52).
intraoperative sedation levels were compared between group i and group ii according to sas. patients in group ii were at deeper sedation level than patients in group i throughout the operation. at 5 min after spinal anesthesia, sas was 5 (4–5) in group i compared with 1 (1–1) in group ii. at 30 min after spinal anesthesia, sas was 4 (3–4) in group i compared with 2 (2–3) in group ii (p<0.001) ([table 5]).
neonatal spinal anesthesia, especially in ex-premature neonates, is gaining popularity and become a common practice in some pediatric surgery departments. the advantages are the avoidance of respiratory depressant drugs used during general anesthesia and eliminating the need for postoperative respiratory support.
in our study, we examined the effect of spinal anesthesia alone without any sedation on the incidence of postoperative apnea. only sugared pacifier was used to sedate the infants. we detected that no patients in this group experienced any attacks of postoperative apnea or bradycardia, and no one needed any postoperative respiratory support. on the contrary, patients who received spinal anesthesia with intravenous sedation (midazolam plus ketamine) and those who received general anesthesia experienced attacks of postoperative apnea and bradycardia (11 patients in group ii and 16 patients in group iii).
multiple previous studies have demonstrated that preterm infants have a higher incidence of respiratory problems than full-term infants. the risk of apnea in preterm infants undergoing inguinal herniorrhaphy increased to 37% following general anesthesia compared with 89% rate for spinal anesthesia with ketamine sedation and 0% apnea rate with spinal anesthesia alone .
many factors are implicated in the development of apneic spell in ex-preterm neonates. these factors include diaphragmatic fatigue, diminished central respiratory drive, hypothermia, anemia, airway obstruction, residual effect of inhaled anesthetic, and muscle relaxant ,.
a study done by wellborn et al.  compared spinal and general anesthesia in former premature infants. the study showed that spinal anesthesia without ketamine sedation was not accompanied with postoperative apnea, whereas neonates receiving general anesthesia or spinal anesthesia with intramuscular ketamine sedation (1–2 mg/kg before placement of the spinal anesthetic) developed 31 and 89% postoperative apnea, respectively .
in infants, metabolic rate of midazolam is lower than in adults. midazolam elimination is approximately 4–6 h in neonates and up to 22 h in premature infants. half-life of midazolam is 3.3-fold longer and clearance is 3.7-fold smaller than in adults .
a study done by frumiento et al.  in 2000 concluded that awake spinal anesthesia, without sedation, reduced the incidence of postoperative apnea and need for respiratory support. it has been documented in the literature that subarachnoid anesthesia itself has a sedating effect. a study done by hermanns et al.  evaluated sedation during spinal anesthesia in infants. one of the possible mechanisms for sedation is decreased afferent conduction to the reticulothalamocortical pathways and hence reduced excitability and arousal to the brain .
in a small randomized trial, williams et al.  compared spinal anesthesia and general anesthesia with sevoflurane on postoperative recovery after inguinal herniotomy in ex-premature infants. they concluded that apnea and bradycardia occurred three times more frequent in the sevoflurane group .
a limitation to our study was that we did not include the preoperative hematocrit level as a risk factor for development of postoperative apnea. anemia (i.e. hematocrit <30%) seemed as an important risk factor predisposing to postoperative apnea. another limiting factor was the short duration of spinal anesthesia in neonates and thus not suitable for long-duration operations.
subarachnoid block without sedation (only sugared pacifier) is an excellent choice for ex-preterm neonates with pca less than 60 weeks undergoing infraumbilical operations allowing calm patients without significant agitation.
kurth cd, lebard se. association of postoperative apnoea, airway obstruction, and hypoxemia in former premature infants. anaesthesiology 1991; 75:22–26.
bayley g. special considerations in the premature and ex-premature infant. anesth int care 2010; 12:91–94.
henderson-smart dj. the effect of gestational age on the incidence and duration of recurrent apnoea in new-born babies. aust paediatr j 1981; 17:273–276.
pillekamp f, hermann c, keller t, von gontard a, kribs a, roth b. factors influencing apnoea and bradycardia of prematurity − implications for neurodevelopment. neonatology 2007; 91:155–161.
cote cj, zaslavsky a, downes jj, kurth cd, welborn lg, warner lo et al. postoperative apnoea in former preterm infants after inguinal herniorrhaphy. a combined analysis. anaesthesiology 1995; 82:809–822.
steer pa, henderson-smart dj. caffeine versus theophylline for apnoea in preterm infants. cochrane database syst rev 2010; 1:cd000273.
welborn lg, rice lj, hannallah rs, broadman lm, ruttimann ue, fink r. postoperative apnea in former preterm infants: prospective comparison of spinal and general anaesthesia. anaesthesiology 1990; 72:838–842.
silins v, julien f, brasher c, nivoche y, mantz j, dahmani s. predictive factors of pacu stay after herniorraphy in infant: a classification and regression tree analysis. paediatr anaesth 2012; 22:230–238.
sale sm, read ja, stoddart pa, wolf ar. prospective comparison of sevoflurane and desflurane in formerly premature infants undergoing inguinal herniotomy. br j anaesth 2006; 96:774–778.
welborn lg, rice lj, hannallah rs, brodman lm, ruttimann ue, fink r. postoperative apnoea in former premature infants: prospective comparison of spinal and general anaesthesia. anaesthesiology 1990; 72:838–842.
young te, neofax mb. a manual of drugs used in neonatal care. 23rd ed. montvale, nj, usa: thomson reuters; 2010.
frumiento c, abajian jc, vane dw. spinal anaesthesia for preterm infants undergoing inguinal hernia repair. arch surg 2000; 135:445–451.
hermanns h, stevens mf, werdehausen r, braun s, lipfert p, jetzek-zader m. sedation during spinal anaesthesia in infants. br j anaesth 2006; 97:380–384.
williams jm, stoddart pa, williams sa, wolf ar. post-operative recovery after inguinal herniotomy in ex-premature infants: comparison between sevoflurane and spinal anaesthetic. br j anaesth 2001; 86:366–371.


text:
Season 2 of the acclaimed hacker drama Mr. Robot gets its premiere on Wednesday, July 1. In the spirit of the show, fans who prefer to stream the episode online will have a few options for doing so. Legally, of course.
Slater won a Golden Globe award for his portrayal of the mysterious Mr. Robot in Season 1, while Malek received a nomination as well.
Fans who have not yet caught up on the events of Season 1 can watch all 10 full episodes streaming for free online with an Amazon Prime subscription at this link. Earlier this year, Amazon Prime purchased exclusive rights to stream episodes of Mr. Robot, which means that Season 1 cannot be accessed via other services such as Netflix or Hulu.
Viewers who missed Season 1 or just need a refresher course on the complex events and multiple plot twists the debut season contained. Those who just want to jump straight into Season 2 without committing to all 10 episodes of the first season can get a quick recap in the video below.
But be warned — this video contains major spoilers for those who have not viewed the first season of Mr. Robot.
The following video is a 30-minute documentary that explores the themes and social importance of Mr. Robot — the first TV drama specifically for and about the digital age. This video also contains spoilers, however.
Finally, the following video is a sneak preview of the much-anticipated Mr. Robot Season 2, which may contain a few spoilers, but only the ones that the show’s creators want to fans to know.
Mr. Robot was created by writer-director Sam Esmail, who, in addition to writing and serving as the “showrunner” of the drama, will now direct every episode of Season 2 — no small feat given that Season 2 will contain 12 episodes, up from 10 in the debut season.
Season 1, which saw Eliot join forces with the underground, anarchist hacker group fSociety to pull off what could be a world-changing infiltration of major financial computer networks, left a multitude of unanswered questions and even to hint at what they are would be to reveal some serious spoilers from Season 1.
Fans will just have to stream the Season 2 premiere online to find out how Mr. Robot plans to answer those questions.
There are a few options to stream the Mr. Robot Season 2 premiere, ” unm4sk-pt1.tc,” online. The episode will stream on the USA Network site at this link as well as on mobile devices by downloading the official USA Network app. Non-cable subscribers can also stream the episode on Wednesday, July 13 via the Sling TV internet TV service, whose Sling Blue package costs $25 per month and carries 40 popular channels, including USA Network. But Sling TV also comes with a seven-day free trial, meaning that fans can stream the Season 2 Mr. Robot premiere legally for free by signing up at this link. Amazon.com, iTunes, and other download services will also offer the premiere, and the entire season, to stream online for $2.99 per episode or $19.99 for the entire season.

lowercased:
season 2 of the acclaimed hacker drama mr. robot gets its premiere on wednesday, july 1. in the spirit of the show, fans who prefer to stream the episode online will have a few options for doing so. legally, of course.
slater won a golden globe award for his portrayal of the mysterious mr. robot in season 1, while malek received a nomination as well.
fans who have not yet caught up on the events of season 1 can watch all 10 full episodes streaming for free online with an amazon prime subscription at this link. earlier this year, amazon prime purchased exclusive rights to stream episodes of mr. robot, which means that season 1 cannot be accessed via other services such as netflix or hulu.
viewers who missed season 1 or just need a refresher course on the complex events and multiple plot twists the debut season contained. those who just want to jump straight into season 2 without committing to all 10 episodes of the first season can get a quick recap in the video below.
but be warned — this video contains major spoilers for those who have not viewed the first season of mr. robot.
the following video is a 30-minute documentary that explores the themes and social importance of mr. robot — the first tv drama specifically for and about the digital age. this video also contains spoilers, however.
finally, the following video is a sneak preview of the much-anticipated mr. robot season 2, which may contain a few spoilers, but only the ones that the show’s creators want to fans to know.
mr. robot was created by writer-director sam esmail, who, in addition to writing and serving as the “showrunner” of the drama, will now direct every episode of season 2 — no small feat given that season 2 will contain 12 episodes, up from 10 in the debut season.
season 1, which saw eliot join forces with the underground, anarchist hacker group fsociety to pull off what could be a world-changing infiltration of major financial computer networks, left a multitude of unanswered questions and even to hint at what they are would be to reveal some serious spoilers from season 1.
fans will just have to stream the season 2 premiere online to find out how mr. robot plans to answer those questions.
there are a few options to stream the mr. robot season 2 premiere, ” unm4sk-pt1.tc,” online. the episode will stream on the usa network site at this link as well as on mobile devices by downloading the official usa network app. non-cable subscribers can also stream the episode on wednesday, july 13 via the sling tv internet tv service, whose sling blue package costs $25 per month and carries 40 popular channels, including usa network. but sling tv also comes with a seven-day free trial, meaning that fans can stream the season 2 mr. robot premiere legally for free by signing up at this link. amazon.com, itunes, and other download services will also offer the premiere, and the entire season, to stream online for $2.99 per episode or $19.99 for the entire season.


text:
Provider of sports touring services. The company sports touring, coaching and training services for sports including basketball, cricket, football, hockey,rugby and tennis.
This information is reserved for PitchBook Platform users. To explore Edwin Doran Sports Tours‘s full profile, request access.

lowercased:
provider of sports touring services. the company sports touring, coaching and training services for sports including basketball, cricket, football, hockey,rugby and tennis.
this information is reserved for pitchbook platform users. to explore edwin doran sports tours‘s full profile, request access.


text:
KB-9281: Running a dzdo Command and Entering a Good Password Can Produce an Error: dzdo: pam_open_session: Permission denied KB-7555: Unable to login as root after upgrade to Centrify Suite 2016 (CDC 5.3.0) KB-4343: Could not load module /usr/share/centrifydc/kerberos/lib64/libgssapi_krb5.a(shr. o.2.2) KB-5180: Does PowerShell module support with DirectControl in classic zones? KB-6041: How to show current license type in use by adclient HOWTO: Install, configure and test the Centrify IBM DB2 SSO Module KB-6040: How to change the license type in use after adclient successful joined to the AD? KB-6073: How to join the Linux/Unix Centrify Server to Active Directory with specific Computer Role? KB-6056: How to report the group policy settings that are in effect for the local computer?
DZDO is failing on RHEL after Centrify DirectControl upgrade from an older version to 5.4.x with error "pam_open_session: module is unknown"
In this scenario, the PAM stack, in the older version of Centrify DirectControl, had this format which included the deprecated 'pam_stack.so' module. It is unclear how this configuration was set, either by client configuration or remnants of a previous version's setup.
DZDO settings have changed from older versions to newer versions, and using a deprecated PAM module can cause unexpected behavior.

lowercased:
kb-9281: running a dzdo command and entering a good password can produce an error: dzdo: pam_open_session: permission denied kb-7555: unable to login as root after upgrade to centrify suite 2016 (cdc 5.3.0) kb-4343: could not load module /usr/share/centrifydc/kerberos/lib64/libgssapi_krb5.a(shr. o.2.2) kb-5180: does powershell module support with directcontrol in classic zones? kb-6041: how to show current license type in use by adclient howto: install, configure and test the centrify ibm db2 sso module kb-6040: how to change the license type in use after adclient successful joined to the ad? kb-6073: how to join the linux/unix centrify server to active directory with specific computer role? kb-6056: how to report the group policy settings that are in effect for the local computer?
dzdo is failing on rhel after centrify directcontrol upgrade from an older version to 5.4.x with error "pam_open_session: module is unknown"
in this scenario, the pam stack, in the older version of centrify directcontrol, had this format which included the deprecated 'pam_stack.so' module. it is unclear how this configuration was set, either by client configuration or remnants of a previous version's setup.
dzdo settings have changed from older versions to newer versions, and using a deprecated pam module can cause unexpected behavior.


text:
On this Wednesday my puppy Summer (12.5 weeks) went to the puppy kindergarten (it was his fourth time), and had two fights with another puppy near the end of the class. There were only three puppies that day -- one is his old buddy, a 3 month old goldendoodle, another one is a new blue heeler puppy (9 weeks old). The first fight was when Summer was holding a toy in his mouth and the new puppy tried to get it. They chased a bit and suddenly they started screaming and fighting! The trainer immediately separated them and gave Summer a time out. After a while they continued playing and chasing each other and the two broke out a fight again. We were so shock!! I never saw Summer like this before. The trainer talked to me seriously, said if this continued Summer will have big problems when he grow up. She asked me about Summer's behavior at home and other places and she was surprised that we only took him out for potty. She said we should not lock a puppy in an apartment even he's not fully vaccinated yet. She suggested to enroll an obedient class ASAP. Also take him out to meet different places like markets, bus and parks etc..
I felt so so bad. Summer is sweet most of the time at home. Sometimes (especially when he is very hyped up) he would bite our hands and attack faces. When I told the trainer about it she said it is a VERY BAD behavior. I think that is normal for a pup especially a shiba? My husband and I are working on it and Summer is slowly improving. We are using the "ouch" and walk away technique. We train and play with him daily to make sure he has plenty of excise. We also let him play a bit on the grass when he is out to potty. We are new to shiba but we are trying our best. Are we doing something wrong? Anyone have similar situations with shiba puppies?
Yes. Actually I found a few scratches on his belly and bottom when we got home.
I'm wondering how familiar the trainers are with Shibas haha, cus Shibas definitely do play rough. The hand biting / nipping sounds all too familiar. :)) Dogs sure aren't immune to receiving scratches during playtime. Was the other dog trying to get away? A pretty clear way to tell when it's fighting and when it's play is to separate the two dogs for a short time, then when you reintroduce them, pay attention to whether they both want to approach each other again or if one of them is trying to avoid the other.
I also used the "ouch" method and would immediately end play when my pup was mouthy. I would kind of have a big reaction, act offended and storm off lol. I learned that he really picked up on my body language.
It's hard to know without seeing, but the trainers don't sound very experienced if they want to kick a dog out of a training class if they aren't already perfectly mannered. That's kind of the point of taking them to classes and socializing with other puppies. I think obedience classes would be fun and a good experience for anyone. Maybe the trainers of the obedience class have more experience and better management than the trainers of this puppy class. I do agree that you should be out socializing the pup even before all the vaccines. We carried our pup everywhere when he was very young and went to every dog friendly place we could find to get him used to seeing the sights and hearing the sounds while being nice and safe and not overwhelmed.
Update: we officially got kicked out today :( The trainers said he is "fearful aggressive"in the class (excuse me? On the first day class she said he was "very confidant" and now is fearful?) and puppy kindergarten is simply too much for him. They suggested we keep carrying him around different places and only have one to one play date.
I'm wondering how familiar the trainers are with Shibas haha, cus Shibas definitely do play rough. The hand biting / nipping sounds all too familiar.
I definitely doubt about their experience of handling a shiba inu. They seemed to know this breed is independent and strong will, but that is all about it.
Thank you for your reply! That's really helpful. I will definitely carry him around different places more often.
Here are some clips when he was the kindergarten. I didn't record when the fights happened so these clips are just normal playing.
Okay, been watching this thread. Those vids are adorable. Actually, I think the class may be a little too strict on what they consider "appropriate", especially after watching the last vid. The pups were playing well with each other and were relaxed--there was no reason to break them up at all at that time.
Japanese in general are very very polite so maybe they want their pets to be "polite" too haha.
@caroline you are welcome ^_^ Considering that I see the same attitude in the US as well, I think it is just a human thing. We have very unrealistic expectations of dogs because of years of bad research, and it will take time to overcome that.

lowercased:
on this wednesday my puppy summer (12.5 weeks) went to the puppy kindergarten (it was his fourth time), and had two fights with another puppy near the end of the class. there were only three puppies that day -- one is his old buddy, a 3 month old goldendoodle, another one is a new blue heeler puppy (9 weeks old). the first fight was when summer was holding a toy in his mouth and the new puppy tried to get it. they chased a bit and suddenly they started screaming and fighting! the trainer immediately separated them and gave summer a time out. after a while they continued playing and chasing each other and the two broke out a fight again. we were so shock!! i never saw summer like this before. the trainer talked to me seriously, said if this continued summer will have big problems when he grow up. she asked me about summer's behavior at home and other places and she was surprised that we only took him out for potty. she said we should not lock a puppy in an apartment even he's not fully vaccinated yet. she suggested to enroll an obedient class asap. also take him out to meet different places like markets, bus and parks etc..
i felt so so bad. summer is sweet most of the time at home. sometimes (especially when he is very hyped up) he would bite our hands and attack faces. when i told the trainer about it she said it is a very bad behavior. i think that is normal for a pup especially a shiba? my husband and i are working on it and summer is slowly improving. we are using the "ouch" and walk away technique. we train and play with him daily to make sure he has plenty of excise. we also let him play a bit on the grass when he is out to potty. we are new to shiba but we are trying our best. are we doing something wrong? anyone have similar situations with shiba puppies?
yes. actually i found a few scratches on his belly and bottom when we got home.
i'm wondering how familiar the trainers are with shibas haha, cus shibas definitely do play rough. the hand biting / nipping sounds all too familiar. :)) dogs sure aren't immune to receiving scratches during playtime. was the other dog trying to get away? a pretty clear way to tell when it's fighting and when it's play is to separate the two dogs for a short time, then when you reintroduce them, pay attention to whether they both want to approach each other again or if one of them is trying to avoid the other.
i also used the "ouch" method and would immediately end play when my pup was mouthy. i would kind of have a big reaction, act offended and storm off lol. i learned that he really picked up on my body language.
it's hard to know without seeing, but the trainers don't sound very experienced if they want to kick a dog out of a training class if they aren't already perfectly mannered. that's kind of the point of taking them to classes and socializing with other puppies. i think obedience classes would be fun and a good experience for anyone. maybe the trainers of the obedience class have more experience and better management than the trainers of this puppy class. i do agree that you should be out socializing the pup even before all the vaccines. we carried our pup everywhere when he was very young and went to every dog friendly place we could find to get him used to seeing the sights and hearing the sounds while being nice and safe and not overwhelmed.
update: we officially got kicked out today :( the trainers said he is "fearful aggressive"in the class (excuse me? on the first day class she said he was "very confidant" and now is fearful?) and puppy kindergarten is simply too much for him. they suggested we keep carrying him around different places and only have one to one play date.
i'm wondering how familiar the trainers are with shibas haha, cus shibas definitely do play rough. the hand biting / nipping sounds all too familiar.
i definitely doubt about their experience of handling a shiba inu. they seemed to know this breed is independent and strong will, but that is all about it.
thank you for your reply! that's really helpful. i will definitely carry him around different places more often.
here are some clips when he was the kindergarten. i didn't record when the fights happened so these clips are just normal playing.
okay, been watching this thread. those vids are adorable. actually, i think the class may be a little too strict on what they consider "appropriate", especially after watching the last vid. the pups were playing well with each other and were relaxed--there was no reason to break them up at all at that time.
japanese in general are very very polite so maybe they want their pets to be "polite" too haha.
@caroline you are welcome ^_^ considering that i see the same attitude in the us as well, i think it is just a human thing. we have very unrealistic expectations of dogs because of years of bad research, and it will take time to overcome that.


text:
Released on November the 22nd of 1968.
If you want me to  I will.
If you want me to-- I will.

lowercased:
released on november the 22nd of 1968.
if you want me to  i will.
if you want me to-- i will.


text:
An upper-second class Honours degree, or overseas equivalent. Applications are also welcome from candidates with significant high calibre industry or government experience.
The MSc in Global Energy Management (GEM) is an intensive course aiming to produce future leaders in the energy sector.
Industries, economies and societies face complex challenges and uncertainties that could become more extreme in the future. Both government and industry need to be able to understand and adapt to this changing context.
Through this course you’ll gain a rigorous analytical training and in-depth real-world knowledge of global energy systems. There’s also hands-on training in the management of energy-related issues. Your training will help to give you an unrivalled edge in the energy job market.

lowercased:
an upper-second class honours degree, or overseas equivalent. applications are also welcome from candidates with significant high calibre industry or government experience.
the msc in global energy management (gem) is an intensive course aiming to produce future leaders in the energy sector.
industries, economies and societies face complex challenges and uncertainties that could become more extreme in the future. both government and industry need to be able to understand and adapt to this changing context.
through this course you’ll gain a rigorous analytical training and in-depth real-world knowledge of global energy systems. there’s also hands-on training in the management of energy-related issues. your training will help to give you an unrivalled edge in the energy job market.


text:
In the online MS in Library and Information Science - Youth Services degree from Drexel University is an excellent option for web developers, knowledge management and Internet content specialists, competitive intelligence experts, or digital librarians who are looking to move into careers within any public library working with youth populations.
Based on a solid backbone of technology, this online library and information science degree will instill in its students the knowledge that is needed for developing and maintaining various types of youth programs within any library.
Drexel University's College of Information Science and Technology, and fully accredited by the American Library Association (ALA), and was ranked by U.S.News & World Report as one of "America's Best Graduate Schools."

lowercased:
in the online ms in library and information science - youth services degree from drexel university is an excellent option for web developers, knowledge management and internet content specialists, competitive intelligence experts, or digital librarians who are looking to move into careers within any public library working with youth populations.
based on a solid backbone of technology, this online library and information science degree will instill in its students the knowledge that is needed for developing and maintaining various types of youth programs within any library.
drexel university's college of information science and technology, and fully accredited by the american library association (ala), and was ranked by u.s.news & world report as one of "america's best graduate schools."


text:
A summer move to Real Madrid is looking more likely than ever.
Jose Mourinho has revealed the one condition that would allow David De Gea to leave Manchester United in the summer.
De Gea has developed into one of the best keepers in the world since arriving at Old Trafford from Atletico Madrid in 2011, and the Spanish ‘keeper has been persistently linked with a move away from the club over recent times.
De Gea kept 14 clean sheets during the course of the 2016/17 season but found himself benched for the Europa League final against Ajax on Wednesday night (March 24).
The 26-year-old has now emerged as a top transfer target for Spanish giants Real Madrid, and Mourinho has reportedly now revealed the one clause that would allow De Gea to leave the club over the summer.
As Marca reports, the United manager is willing to sell De Gea to Los Blancos as long as the club can agree £22m and striker Alvero Morata for the ‘keeper in a part-exchange deal.
Mourinho allegedly values De Gea at £65m, which suggests he believes Spanish international Morata to be worth £43m.
However, Real are reportedly unwilling to sell Morata for anything less that £65m, which could prevent a possible swap deal taking place.
Morata has found his first-team opportunities limited at Real this year, but the striker has still managed to score 15 goals in just 14 starts this season.
The 24-year-old began his career at Real, before leaving for Juventus in 2014. However, he was bought back by the club last year for €30 million after impressing during his time in Serie A.
He has proven himself to be prolific for both club and country, netting 8 goals in 19 appearances for Spain.
However, rumours have also emerged linking Morata with moves to AC Milan and Chelsea, which could scupper any potential switch to Old Trafford.
So, until Mourinho and Real boss Zinedine Zidane can agree to compromise on price, De Gea and Morata may well end up staying put next season.

lowercased:
a summer move to real madrid is looking more likely than ever.
jose mourinho has revealed the one condition that would allow david de gea to leave manchester united in the summer.
de gea has developed into one of the best keepers in the world since arriving at old trafford from atletico madrid in 2011, and the spanish ‘keeper has been persistently linked with a move away from the club over recent times.
de gea kept 14 clean sheets during the course of the 2016/17 season but found himself benched for the europa league final against ajax on wednesday night (march 24).
the 26-year-old has now emerged as a top transfer target for spanish giants real madrid, and mourinho has reportedly now revealed the one clause that would allow de gea to leave the club over the summer.
as marca reports, the united manager is willing to sell de gea to los blancos as long as the club can agree £22m and striker alvero morata for the ‘keeper in a part-exchange deal.
mourinho allegedly values de gea at £65m, which suggests he believes spanish international morata to be worth £43m.
however, real are reportedly unwilling to sell morata for anything less that £65m, which could prevent a possible swap deal taking place.
morata has found his first-team opportunities limited at real this year, but the striker has still managed to score 15 goals in just 14 starts this season.
the 24-year-old began his career at real, before leaving for juventus in 2014. however, he was bought back by the club last year for €30 million after impressing during his time in serie a.
he has proven himself to be prolific for both club and country, netting 8 goals in 19 appearances for spain.
however, rumours have also emerged linking morata with moves to ac milan and chelsea, which could scupper any potential switch to old trafford.
so, until mourinho and real boss zinedine zidane can agree to compromise on price, de gea and morata may well end up staying put next season.


text:
This Thursday, many of us will gather around tables piled high with turkey, sweet potatoes and pumpkin pie. More importantly, we will pause to reflect on what we are thankful for and what we can do to help those who are less fortunate. From stocking the shelves of food pantries to wrapping gifts for children in need, the holiday season is a time of year when the spirit of compassion and generosity of American families is particularly apparent.
This has been especially true in the last few weeks, as the United States has rallied a swift and life-saving response in the Philippines, where Typhoon Haiyan killed more than 4,000 people. Our disaster response teams – civilian and military – have already reached tens of thousands of survivors. Less than ten days after the storm made landfall, we had the water system up and running in hardest-hit Tacloban, supplying 200,000 people with clean water. “Our military personnel and USAID team do this better than anybody in the world,” President Obama shared in a video message. I couldn’t agree more. In these moments of crisis, we’re proud to represent our nation’s tradition of generosity, especially as we celebrate a holiday with its roots in the spirit of gratitude.
At the end of the day, we remain committed to ensuring our assistance not only saves lives today, but reduces the risk of disaster tomorrow. From Syria (PDF) to Somalia, we’re working to bring long-term food security to the 840 million people around the world who go to bed hungry every night. We’re also working to reduce the high rates of poor nutrition that contribute to nearly half of all deaths in children under the age of five each year.
In the last year, we have directly helped more than 9 million households transform their farms and fields with our investments in agriculture and food security through Feed the Future. We’ve also reached 12 million children with nutrition programs that can prevent and treat undernutrition and improve child survival. While there is still a lot of work to be done, we’re helping transform the face of poverty and hunger around the world – advancing progress toward the Millennium Development Goal to halve the prevalence of hunger by 2015, a target that’s within reach if the global community continues to strengthen our focus and energy.
We know that hunger is not hopeless. It is solvable. If we continue to invest in smallholder farmers – especially women – and support good nutrition during the critical 1,000-day window from pregnancy to a child’s second birthday, we can meet the global challenge of sustainably increasing agricultural production for a growing population. By scaling up promising innovations from farm to market to table, we can tackle extreme poverty by the roots and shape a future of prosperity and progress.
This week, we’re thankful for the opportunity to be a part of this collective global effort and wish you and your families a happy Thanksgiving.
Want to be part of the solution to hunger and poverty? Find out how you can help contribute to typhoon relief efforts in the Philippines or learn more about how to get involved with Feed the Future. Led by USAID, Feed the Future draws on the agricultural, trade, investment, development and policy resources and expertise of 10 federal agencies. Learn more about USAID’s long history of leadership in agricultural development.

lowercased:
this thursday, many of us will gather around tables piled high with turkey, sweet potatoes and pumpkin pie. more importantly, we will pause to reflect on what we are thankful for and what we can do to help those who are less fortunate. from stocking the shelves of food pantries to wrapping gifts for children in need, the holiday season is a time of year when the spirit of compassion and generosity of american families is particularly apparent.
this has been especially true in the last few weeks, as the united states has rallied a swift and life-saving response in the philippines, where typhoon haiyan killed more than 4,000 people. our disaster response teams – civilian and military – have already reached tens of thousands of survivors. less than ten days after the storm made landfall, we had the water system up and running in hardest-hit tacloban, supplying 200,000 people with clean water. “our military personnel and usaid team do this better than anybody in the world,” president obama shared in a video message. i couldn’t agree more. in these moments of crisis, we’re proud to represent our nation’s tradition of generosity, especially as we celebrate a holiday with its roots in the spirit of gratitude.
at the end of the day, we remain committed to ensuring our assistance not only saves lives today, but reduces the risk of disaster tomorrow. from syria (pdf) to somalia, we’re working to bring long-term food security to the 840 million people around the world who go to bed hungry every night. we’re also working to reduce the high rates of poor nutrition that contribute to nearly half of all deaths in children under the age of five each year.
in the last year, we have directly helped more than 9 million households transform their farms and fields with our investments in agriculture and food security through feed the future. we’ve also reached 12 million children with nutrition programs that can prevent and treat undernutrition and improve child survival. while there is still a lot of work to be done, we’re helping transform the face of poverty and hunger around the world – advancing progress toward the millennium development goal to halve the prevalence of hunger by 2015, a target that’s within reach if the global community continues to strengthen our focus and energy.
we know that hunger is not hopeless. it is solvable. if we continue to invest in smallholder farmers – especially women – and support good nutrition during the critical 1,000-day window from pregnancy to a child’s second birthday, we can meet the global challenge of sustainably increasing agricultural production for a growing population. by scaling up promising innovations from farm to market to table, we can tackle extreme poverty by the roots and shape a future of prosperity and progress.
this week, we’re thankful for the opportunity to be a part of this collective global effort and wish you and your families a happy thanksgiving.
want to be part of the solution to hunger and poverty? find out how you can help contribute to typhoon relief efforts in the philippines or learn more about how to get involved with feed the future. led by usaid, feed the future draws on the agricultural, trade, investment, development and policy resources and expertise of 10 federal agencies. learn more about usaid’s long history of leadership in agricultural development.


text:
The ultimate in luxurious comfort and quality, our faux fur blankets are a beautiful illusion of nature, mirroring rich animal furs. These are exceptionally woven from the finest materials for the softest feel. Our faux fur blankets emulate both the softness and color of genuine fur.
Care instructions: Machine Wash Cold, Air Fluff Dry.

lowercased:
the ultimate in luxurious comfort and quality, our faux fur blankets are a beautiful illusion of nature, mirroring rich animal furs. these are exceptionally woven from the finest materials for the softest feel. our faux fur blankets emulate both the softness and color of genuine fur.
care instructions: machine wash cold, air fluff dry.


text:
Here Oasis Academy Nunsthorpe, Sutcliffe Avenue, Grimsby, DN33 1AW, is put into focus to show its scores in relation to other schools in the area.
The open date and status above indicate when Oasis Academy Nunsthorpe opened or when it changed to its most recent incarnation, with a number of schools converting to academies in recent years. Where schools have changed type recently, data for previous years covering their previous incarnation is included below as well - so a school may have a status of New due to converting to an academy but have data for previous years prior to conversion.
What type of school is Oasis Academy Nunsthorpe?
How Oasis Academy Nunsthorpe scores on each indicator.
Oasis Academy Nunsthorpe has been rated as Requires Improvement at its most recent Ofsted inspection.
How does Oasis Academy Nunsthorpe perform on each of the areas inspected by Ofsted? As of September 2012, a score of 3 changed from indicating Satisfactory to Requires Improvement.
In 2018, 56% of pupils at Oasis Academy Nunsthorpe reached the expected standard in reading, writing and maths.
How have pupils at Oasis Academy Nunsthorpe done in assessments at the end of Key Stage 2 and how does it compare to local authority and national averages?
While pupils are generally aiming to be working at the expected level in reading, writing and maths, what proportion of children at Oasis Academy Nunsthorpe had a high score in reading and maths and were working at greater depth in writing, and how does this compare to performance at local and national level?
How do children at Oasis Academy Nunsthorpe with different levels of attainment at Key Stage 1 and pupils from disadvantaged backgrounds perform in terms of reaching the expected standard in reading, writing and maths?
How does the % of boys and girls at Oasis Academy Nunsthorpe achieving the expected standard in reading, writing and maths compare to the national average?
What is the pupil:teacher ratio at Oasis Academy Nunsthorpe and how does it compare to the national average?
At Oasis Academy Nunsthorpe, pupils had an average progress score in maths in 2018 that was -0.3 compared to the national average of 0.
At Oasis Academy Nunsthorpe, pupils had an average progress score in reading in 2018 that was 0.2 compared to the national average of 0.
At Oasis Academy Nunsthorpe, pupils had an average progress score in writing in 2018 that was 1.2 compared to the national average of 0.
In 2016/17, the most recent full school year, 3.5% of half-day sessions were missed by pupils at Oasis Academy Nunsthorpe. Nationally, primary school pupils missed 4% of half-day sessions.
How much does Oasis Academy Nunsthorpe spend per pupil on teachers and educational support staff and how does this compare to the average spending across North East Lincolnshire?
What percentage of the budget at Oasis Academy Nunsthorpe is spent on supply staff?

lowercased:
here oasis academy nunsthorpe, sutcliffe avenue, grimsby, dn33 1aw, is put into focus to show its scores in relation to other schools in the area.
the open date and status above indicate when oasis academy nunsthorpe opened or when it changed to its most recent incarnation, with a number of schools converting to academies in recent years. where schools have changed type recently, data for previous years covering their previous incarnation is included below as well - so a school may have a status of new due to converting to an academy but have data for previous years prior to conversion.
what type of school is oasis academy nunsthorpe?
how oasis academy nunsthorpe scores on each indicator.
oasis academy nunsthorpe has been rated as requires improvement at its most recent ofsted inspection.
how does oasis academy nunsthorpe perform on each of the areas inspected by ofsted? as of september 2012, a score of 3 changed from indicating satisfactory to requires improvement.
in 2018, 56% of pupils at oasis academy nunsthorpe reached the expected standard in reading, writing and maths.
how have pupils at oasis academy nunsthorpe done in assessments at the end of key stage 2 and how does it compare to local authority and national averages?
while pupils are generally aiming to be working at the expected level in reading, writing and maths, what proportion of children at oasis academy nunsthorpe had a high score in reading and maths and were working at greater depth in writing, and how does this compare to performance at local and national level?
how do children at oasis academy nunsthorpe with different levels of attainment at key stage 1 and pupils from disadvantaged backgrounds perform in terms of reaching the expected standard in reading, writing and maths?
how does the % of boys and girls at oasis academy nunsthorpe achieving the expected standard in reading, writing and maths compare to the national average?
what is the pupil:teacher ratio at oasis academy nunsthorpe and how does it compare to the national average?
at oasis academy nunsthorpe, pupils had an average progress score in maths in 2018 that was -0.3 compared to the national average of 0.
at oasis academy nunsthorpe, pupils had an average progress score in reading in 2018 that was 0.2 compared to the national average of 0.
at oasis academy nunsthorpe, pupils had an average progress score in writing in 2018 that was 1.2 compared to the national average of 0.
in 2016/17, the most recent full school year, 3.5% of half-day sessions were missed by pupils at oasis academy nunsthorpe. nationally, primary school pupils missed 4% of half-day sessions.
how much does oasis academy nunsthorpe spend per pupil on teachers and educational support staff and how does this compare to the average spending across north east lincolnshire?
what percentage of the budget at oasis academy nunsthorpe is spent on supply staff?


text:
Charlize demonstrates (bottom center) that a pixie work with waves. Creating that touchable volume is simple. Think of it as a blowout for short hair. Rough dry hair to get that natural wave, then... If you were to speak with a make-up artist or hair stylist about the most “ideal” face shapes there are, you’re definitely going to hear them mention oval in the top three.
If you want to sew layered pixie skirts, lightweight fabrics like chiffon or tulle will effectively create an airy look. Cut squares of fabric to give the handkerchief edges of the skirt flare. Pixies don't always don a traditional "fairy" look, so pairings of bright bold colors are appropriate if how to cook chicken wings on the grill Pixie cuts are definitely a fire look, but they can be annoying as they grow out. Any of these styles will keep you on your A game, even when your hair isn’t cooperating. Any of these styles will keep you on your A game, even when your hair isn’t cooperating.
A cool-toned pixie cut should turn heads, and a long bang will add some mystery to your wavy pixie cut. #2: Sassy Pixie for Curly Hair Not everyone can pull off super short bangs, but if you have the bombshell facial structure to make it work (perfectly arched brows, full lips and high cheekbones) they can actually add a welcome bit of whimsy to your overall appearance.
40. Messy Twist. Thats all for this time. Before you do this haircut move, make sure that you will be happy with the result. You need a proper communication with your hairdresser and consider to use long hour experinced salon for this one.

lowercased:
charlize demonstrates (bottom center) that a pixie work with waves. creating that touchable volume is simple. think of it as a blowout for short hair. rough dry hair to get that natural wave, then... if you were to speak with a make-up artist or hair stylist about the most “ideal” face shapes there are, you’re definitely going to hear them mention oval in the top three.
if you want to sew layered pixie skirts, lightweight fabrics like chiffon or tulle will effectively create an airy look. cut squares of fabric to give the handkerchief edges of the skirt flare. pixies don't always don a traditional "fairy" look, so pairings of bright bold colors are appropriate if how to cook chicken wings on the grill pixie cuts are definitely a fire look, but they can be annoying as they grow out. any of these styles will keep you on your a game, even when your hair isn’t cooperating. any of these styles will keep you on your a game, even when your hair isn’t cooperating.
a cool-toned pixie cut should turn heads, and a long bang will add some mystery to your wavy pixie cut. #2: sassy pixie for curly hair not everyone can pull off super short bangs, but if you have the bombshell facial structure to make it work (perfectly arched brows, full lips and high cheekbones) they can actually add a welcome bit of whimsy to your overall appearance.
40. messy twist. thats all for this time. before you do this haircut move, make sure that you will be happy with the result. you need a proper communication with your hairdresser and consider to use long hour experinced salon for this one.


text:
being pro-peace, but not to the point that advocating for Israeli concessions damages Israel’s existence.
Lee, please clarify: Is any person or organization a) who criticized and disrespected the decision of the democratically elected Israeli government to disengage from Gaza and/or b) who criticized and disrespected the Israeli military in its judgment that it could protect the citizens of Israel after disengagement from Gaza — not to be considered pro-Israel by your definition?
For a variety of reasons, very few pro-Israel advocates I know favored Israel’s unilateral Gaza disengagement policy; some exhibited disrespect in their criticism.

lowercased:
being pro-peace, but not to the point that advocating for israeli concessions damages israel’s existence.
lee, please clarify: is any person or organization a) who criticized and disrespected the decision of the democratically elected israeli government to disengage from gaza and/or b) who criticized and disrespected the israeli military in its judgment that it could protect the citizens of israel after disengagement from gaza — not to be considered pro-israel by your definition?
for a variety of reasons, very few pro-israel advocates i know favored israel’s unilateral gaza disengagement policy; some exhibited disrespect in their criticism.


text:
No great event is created by one individual, it takes a unified team to get behind one idea, an idea our founder had some 10 years ago which is now exploited successfully across multiple industries.
Together we work hard, play hard, laugh out loud hard and along the way deliver the best events in the world.
Everything starts at Production, the architects behind our events. They research content, interview potential speakers and build great event programmes.
Our Client Managers are top marketeers, they invite pre selected guests to our forums, have great relationships with hundreds of key decision makers and leave no stone unturned. This leads to us having high quality delegates and meaningful conversations at the events.
Looking after our delegates, managing diaries, planning travel, arranging any special requirements falls under our customer care crew. Having good attention to detail, patience, great admin, clear communication & fab product knowledge of our events ensures our customer service levels are top notch.
Our vendors sponsor our events, vendor care is the one stop shop for anything relating to the smooth outcomes at the forums. From orientation calls for new sponsors through to getting the detail right on package delivery the vendor care team ensure our event sponsors have a great experience and connect seamlessly with our delegate clients.
Knock Knock, Who's there? Email? Email who?? Click Delete/ return to work, we’ve all been there. Our super smart marketeers dont do spam. Setting the marketing strategy, getting our value proposition out to relevant pre-defined clients and only those who have opted in to receive communications is their gameplan. Distributing insightful market trend analysis and vital communications to our customers is all in a days work for our marketing heros.
Chilled sales, not boiler room. Our product speaks for itself. The business development team engage with new and existing customers, recommend very defined solutions that make logical sense. We don’t smash square pegs into round holes. If we call someone there is an absolute fit and we have the evidence to back it up, that’s why 92% of our vendors rebook within 9 months and most come back and book multiple events.
Our Top Management are responsible for the smooth running of our business and head up various divisions within the organisation. All have been promoted from within, and deliver a unified vision for excellence and integrity across all our departments and job functions.
Perks of the job? We’ve got it covered.
Retro Arcades, Table tennis battles. Pool sharks welcome.
Stocked food kitchen, free soft drinks on tap. Catered lunches.
Go travelling, come back. Paid holidays, Whopping 17 days off at Xmas.
Dubai, Vegas, Sicily, Cannes. Where next?
Michelin star restaurants every month. Unlimited food & drinks, Yey!.
On site Gym. Keep Fit. Stay Trim. Pump those Guns.
Cirque Du Soleil. Go Karting. Theme Park adventures.
From Ah!Media Academy to ongoing training, we invest and support.
Yes we are target driven, we pay handsome commissions to help with your life goals.
If you are good at your job it shows, 100% of our top Management are promoted from within.
At Ah!media you will make an impact. You will make a difference. You will be recognised as an individual.

lowercased:
no great event is created by one individual, it takes a unified team to get behind one idea, an idea our founder had some 10 years ago which is now exploited successfully across multiple industries.
together we work hard, play hard, laugh out loud hard and along the way deliver the best events in the world.
everything starts at production, the architects behind our events. they research content, interview potential speakers and build great event programmes.
our client managers are top marketeers, they invite pre selected guests to our forums, have great relationships with hundreds of key decision makers and leave no stone unturned. this leads to us having high quality delegates and meaningful conversations at the events.
looking after our delegates, managing diaries, planning travel, arranging any special requirements falls under our customer care crew. having good attention to detail, patience, great admin, clear communication & fab product knowledge of our events ensures our customer service levels are top notch.
our vendors sponsor our events, vendor care is the one stop shop for anything relating to the smooth outcomes at the forums. from orientation calls for new sponsors through to getting the detail right on package delivery the vendor care team ensure our event sponsors have a great experience and connect seamlessly with our delegate clients.
knock knock, who's there? email? email who?? click delete/ return to work, we’ve all been there. our super smart marketeers dont do spam. setting the marketing strategy, getting our value proposition out to relevant pre-defined clients and only those who have opted in to receive communications is their gameplan. distributing insightful market trend analysis and vital communications to our customers is all in a days work for our marketing heros.
chilled sales, not boiler room. our product speaks for itself. the business development team engage with new and existing customers, recommend very defined solutions that make logical sense. we don’t smash square pegs into round holes. if we call someone there is an absolute fit and we have the evidence to back it up, that’s why 92% of our vendors rebook within 9 months and most come back and book multiple events.
our top management are responsible for the smooth running of our business and head up various divisions within the organisation. all have been promoted from within, and deliver a unified vision for excellence and integrity across all our departments and job functions.
perks of the job? we’ve got it covered.
retro arcades, table tennis battles. pool sharks welcome.
stocked food kitchen, free soft drinks on tap. catered lunches.
go travelling, come back. paid holidays, whopping 17 days off at xmas.
dubai, vegas, sicily, cannes. where next?
michelin star restaurants every month. unlimited food & drinks, yey!.
on site gym. keep fit. stay trim. pump those guns.
cirque du soleil. go karting. theme park adventures.
from ah!media academy to ongoing training, we invest and support.
yes we are target driven, we pay handsome commissions to help with your life goals.
if you are good at your job it shows, 100% of our top management are promoted from within.
at ah!media you will make an impact. you will make a difference. you will be recognised as an individual.


text:
Chris Sprowls focuses his practice on litigation.
Chris joined Buchanan from the State Attorney’s Office for Florida’s Sixth Judicial Circuit, where he spent seven years as an Assistant State Attorney. Chris was assigned to the Special Prosecution Unit where he focused on gang and homicide crime, taking an active role in identifying gangs and dismantling their criminal networks. During his time as a prosecutor, Chris tried dozens of jury trials, many involving first degree murder. Among Chris’ most notable trial victories was the conviction of an individual who drove her car into a front yard striking three triplet little girls as well as the conviction of William Hurst for the 1982 murder of his wife. Chris also served as Director of the Veterans Treatment Court for Pinellas and Pasco counties and oversaw both the agency’s offices in Pasco County.
On November 4, 2014, Chris was elected to the Florida House of Representatives, representing the 65th District and continues to serve in that capacity.

lowercased:
chris sprowls focuses his practice on litigation.
chris joined buchanan from the state attorney’s office for florida’s sixth judicial circuit, where he spent seven years as an assistant state attorney. chris was assigned to the special prosecution unit where he focused on gang and homicide crime, taking an active role in identifying gangs and dismantling their criminal networks. during his time as a prosecutor, chris tried dozens of jury trials, many involving first degree murder. among chris’ most notable trial victories was the conviction of an individual who drove her car into a front yard striking three triplet little girls as well as the conviction of william hurst for the 1982 murder of his wife. chris also served as director of the veterans treatment court for pinellas and pasco counties and oversaw both the agency’s offices in pasco county.
on november 4, 2014, chris was elected to the florida house of representatives, representing the 65th district and continues to serve in that capacity.