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OBJECTIVE Anterior cervical discectomy and fusion (ACDF) is often described as the gold standard surgical technique for cervical spondylotic radiculopathy. Although outcomes are considered favorable, there is little prognostic evidence to guide patient selection for ACDF. This study aimed to 1) describe the 24-month postoperative trajectories of arm pain, neck pain, and pain-related disability; and 2) identify perioperative prognostic factors that predict trajectories representing poor clinical outcomes. METHODS In this retrospective cohort study, patients with cervical spondylotic radiculopathy who underwent ACDF at 1 of 12 orthopedic or neurological surgery centers were recruited. Potential outcome predictors included demographic, health, clinical, and surgery-related prognostic factors. Surgical outcomes were classified by trajectories of arm pain intensity, neck pain intensity (numeric pain rating scales), and pain-related disability (Neck Disability Index) from before surgery to 24 months postsurgery. Trajectories of postoperative pain and disability were estimated with latent class growth analysis, and prognostic factors associated with poor outcome trajectory were identified with robust Poisson models. RESULTS The authors included data from 352 patients (mean age 50.9 [SD 9.5] years; 43.8% female). The models estimated that 15.5%–23.5% of patients followed a trajectory consistent with a poor clinical outcome. Lower physical and mental health–related quality of life, moderate to severe risk of depression, and longer surgical wait time and procedure time predicted poor postoperative trajectories for all outcomes. Receiving compensation and smoking additionally predicted a poor neck pain outcome. Regular exercise, physiotherapy, and spinal injections before surgery were associated with a lower risk of poor disability outcome. Patients who used daily opioids, those with worse general health, or those who reported predominant neck pain or a history of depression were at greater risk of poor disability outcome. CONCLUSIONS Patients who undergo ACDF for cervical spondylotic radiculopathy experience heterogeneous postoperative trajectories of pain and disability, with 15.5%–23.5% of patients experiencing poor outcomes. Demographic, health, clinical, and surgery-related prognostic factors can predict ACDF outcomes. This information may further assist surgeons with patient selection and with setting realistic expectations. Future studies are needed to replicate and validate these findings prior to confident clinical implementation.

Study Design Retrospective cohort. Objectives To compare outcomes of minimally invasive surgery (MIS) vs open surgery (OPEN) for lumbar spinal stenosis (LSS) in patients with diabetes. Methods Patients with diabetes who underwent spinal decompression alone or with fusion for LSS within the Canadian Spine Outcomes and Research Network (CSORN) database were included. MIS vs OPEN outcomes were compared for 2 cohorts: (1) patients with diabetes who underwent decompression alone (N = 116; MIS n = 58 and OPEN n = 58), (2) patients with diabetes who underwent decompression with fusion (N = 108; MIS n = 54 and OPEN n = 54). Modified Oswestry Disability Index (mODI) and back and leg pain were compared at baseline, 6–18 weeks, and 1-year post-operation. The number of patients meeting minimum clinically important difference (MCID) or minimum pain/disability at 1-year was compared. Results MIS approaches had less blood loss (decompression alone difference 100 mL, P = .002; with fusion difference 244 mL, P < .001) and shorter length of stay (LOS) (decompression alone difference 1.2 days, P = .008; with fusion difference 1.2 days, P = .026). MIS compared to OPEN decompression with fusion had less patients experiencing adverse events (AEs) (difference 13 patients, P = .007). The MIS decompression with fusion group had lower 1-year mODI (difference 14.5, 95% CI [7.5, 21.0], P < .001) and back pain (difference 1.6, 95% CI [.6, 2.7], P = .002) compared to OPEN. More patients in the MIS decompression with fusion group exceeded MCID at 1-year for mODI (MIS 75.9% vs OPEN 53.7%, P = .028) and back pain (MIS 85.2% vs OPEN 70.4%, P = .017). Conclusions MIS approaches were associated with more favorable outcomes for patients with diabetes undergoing decompression with fusion for LSS.

Software Defined Networking (SDN) presents an extremely rare point of inflection which offers the potential to leverage the economics of SDN to harden the network as a whole. Utilizing this inflection point requires security technologies that have two characteristics. First, security technologies must be incentive-aligned for initial adoption. Securing SDN requires designing technologies that provide immediate returns for the early adopters. Compare with BGPSEC, which helps only peers and not the investing organization. We have a demonstration providing risk-aware routing given the previous RIB. Second, the technologies must function without complete adoption. And of course, third, these must be resilient against attack. Compare with egress filtering, which works with ISP adoption. We offer a proof of concept showing herd immunity to classes of DoS attacks with partial adoption by second-tier ISP s. Failing to secure next-generation networks risks increasingly vulnerable cyber=physical systems, including homes and even individual persons as the internet of things is diffused to households and surgeries. We focused on six use cases: data centers, then large ISPs, an IXP case, two cyber-physical cases, and the case of the next generation battlefield. The two cyber-physical cases were international airports and industrial control systems.

SubmergingPhaseolus vulgariscv. Top Crop seed in air-saturated water for 16 h markedly depresses subsequent germination. This is termed soaking injury. The postulate by Norton (1986) that soak-injured seeds merely run out of available energy was investigated. Soaking in air-saturated water reduced the total respiration (VT; in terms of O2uptake) of excised axes and cotyledons resulting in lower ATP levels. The contribution of both the mitochondrial cytochrome respiratory pathway (VCYT) and the alternative respiratory pathway (VALT) to the total respiration (VT) was significantly lower in these axes. However, the adenylate energy charge (AEC) values for both axes and cotyledons excised from soak-injured seeds did not drop below 0.6, the threshold value indicating death of plant material. Differences between the ultrastructure of mitochondria in the radicle tips of axes from unsoaked and water-soaked seeds were observed. However, the capacity to operate the Krebs cycle was similar in all axes and soak-injured seeds were still capable of germinating when the testas were removed or the seeds dried. This means that axes contained a sufficient amount of carbohydrates and potential energy to germinate after soaking. Moreover, soak-injured seeds produced ethanol at a rate which was five times higher than that of unsoaked control seeds, both during the soaking and post-soaking periods. Together with the low rate of oxygen consumption by soak-injured seeds during the same soaking and incubation time, it appears that soak-injured seeds lack the potential to switch from an anaerobic to an aerobic respiration pattern causing low ATP levels in these axes. It is speculated that the latter seems to be the result of limited pyruvate supply, probably due to accelerated and prolonged fermentation or futile combustion through other pathways or both.

This study evaluates loss to follow-up in a methadone maintenance treatment (MMT) program for patients dependent on opioid analgesics in a community in eastern Canada. Data were collected using the Addiction Severity Index Lite. The probability of loss to follow-up was evaluated using a time-to-event analysis. Involuntary and voluntary program discharges were treated separately as the outcomes of interest. Multivariate Cox proportional hazards models were used to explore the role of various patient-related attributes. The probabilities of involuntary and voluntary discharges at 1 year were 20% and 14%, respectively. In this exploratory analysis, determinants of loss to follow-up were characteristics related to drug use history (e.g., use of sedatives) and its consequences (e.g., number of lifetime arrests), and differed for each outcome. Some determinants of involuntary discharge were modified by sex. Understanding predictors of specific loss to follow-up outcomes may help MMT programs improve patient retention.

Seed germination of Grand Rapids lettuce (Lactuca sativa L.) was inhibited at 38°C (thermoinhibition). Thermoinhibition was totally relieved by a combination of 100% oxygen and 10 mg I−1 kinetin, to a lesser extent by a combination of oxygen and ethylene but not at all by oxygen plus GA3. The combination of oxygen with kinetin or ethylene was more effective in preventing thermoinhibition than a combination of all three hormones and CO2 in air. The beneficial effect of oxygen plus kinetin was not related to either increased production of CO2 or ethylene by the seeds. In air, germination was partially inhibited by 2-aminoethoxyvinyl glycine (AVG) or 2,5-norbornadiene (NBD) and totally inhibited by AVG plus NBD. Oxygen plus kinetin almost completely alleviated their inhibitory effects. It was concluded that oxygen plus kinetin caused seeds to bypass an ethylene requirement for germination or increased the sensitivity of seeds to ethylene. In air at 38°C, seeds exhibited a high level of ethanolic fermentation, while in oxygen plus kinetin they respired aerobically. At 38°C in air, contents of ATP and total adenylates were reduced, while in seeds treated with oxygen plus kinetin these contents were similar or higher than in 25°C controls. A similar response was also observed for adenylate energy charge. It was concluded that part of the mechanism of thermoinhibition could be the failure of ATP content to reach a sufficient level to satisfy the requirement for germination at 38°C. It appeared possible that the prevention of thermoinhibition by oxygen plus kinetin could be related to increased ATP content in seeds caused by this treatment.

Submerging Phaseolus vulgaris cv. Top Crop seeds in air-saturated water for 16 h markedly depresses subsequent germination. This is termed soaking injury. Soaking injury does not occur in seeds soaked in CO2-saturated water. Previous studies have shown that soaking injury can be alleviated by drying seeds or removing seed coats. Submergence therefore leads to a situation in bean seeds which is similar to secondary dormancy.As with dormant seeds, C6/C1 ratios of embryonic axes of seeds soaked in air-saturated water remained high (0.8–1.0) during and after soaking. This was paralleled by low activities of glucose-6-phosphate dehydrogenase (EC.1.1.49) and 6-phosphogluconate dehydrogenase (EC 1.1.1.44). In axes of seeds soaked in CO2-saturated water and in unsoaked seeds C6/C1 ratios declined steadily during soaking/imbibition and reached values of around 0.3 after germination. Slight increases ofglucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities occurred in the pre-germination phase. This was followed by a massive increase after radicle emergence. Synthesis of the plastid isoenzymes was a post-germinative event.It appears that soaking injury depresses protein synthesis. Lack of oxidative pentose phosphate pathway activity appears to be a causative factor in soaking injury.

Grand Rapids lettuce (Lactuca saliva L.) seeds entered into a state of secondary dormancy (thermodormancy) when they were imbibed at 40°C for 72 h. The effect of 40°C in inducing thermodormancy was largely reduced by imbibing seeds at 40°C in solutions of polyethylene glycol (PEG), mannitol and NaCl. Despite similar water potentials of solutions, NaCl pretreatment was more effective. Subsequent germination in the dark at 25°C of saline, high-temperature-pretreated seeds required only gibberellic acid (GA3), as was the case with nonthermodormant seeds. Thermodormancy reduced total respiratory capacity (VT) and increased the ratio of alternate pathway (Valt) to cytochrome pathway (Vcyt) respiration. This was prevented by saline pretreatment. Ethylene production and protein synthesis were depressed in thermodormant seeds, and this was partly alleviated by saline pretreatment. The patterns of protein synthesis in saline- and nonsaline-freated seeds at 40°C were similar, differing only in that the saline treated seeds produced in addition a 78 kDa polypeptide. The pattern of protein synthesis at 40°C differed significantly from that at 25°C.

Betaglycan (Tgfbr3) is a coreceptor for transforming growth factor-beta (TGFB) superfamily ligands. In the current study, a defect in seminiferous cord formation was detected in 12.5-13.5 days postcoitum (dpc) beta glycan null murine testis. Immunohistochemistry with antibodies against cell-specific markers revealed defects in somatic cell populations. To confirm these data, quantitative real-time PCR was performed to determine changes in the expression levels of genes involved in fetal testis cell differentiation and function. The expression levels of the Leydig cell markers Insl3, Cyp17a1, Cyp11a1, Star, and Hsd3b1 were reduced in knockout testis compared to wild-type testis, beginning at 12.5 dpc. Whole mount in situ hybridization confirmed that Cyp11a1 expression was reduced in the null testis, but its distribution pattern was unchanged. Apoptosis was not affected by the loss of beta glycan, but proliferation within the interstitium was reduced at 14.5 dpc. However, morphometric analysis showed no changes in Leydig cell counts between the wild-type and the knockout testes at 14.5 dpc, indicating that fetal Leydig function, rather than number, was affected by the loss of beta glycan. The expression levels of Sertoli cell markers Dhh, Sox9, and Amh were also reduced in the knockout testis at 14.5 dpc. However, the expression of fetal germ cell markers Pou5f1 and DDX4 were not changed across the genotypes at any age examined. Our data show that the presence of beta glycan is required for normal cord formation, normal fetal Leydig cell development, and the establishment of fetal testis endocrine function, thus implicating TGFB superfamily members as regulators of early fetal testis structure and function.

Prolonged imbibition and incubation of lettuce seeds at a supraoptimal temperature induces secondary dormancy. Such seeds no longer germinate when returned to conditions optimal for germination of non-dormant seeds. The possibility that inhibitors are involved in the induction of thermodormancy was investigated.Washing of thermodormant seeds restored germination to a small extent. However, continuous leaching of seeds during high-temperature treatment with distilled water, largely prevented the induction of thermodormancy. Such seeds were qualitatively similar to nondormant seeds, i.e. they required only light to germinate at a lower temperature and germinated in the dark if given GA3. The germination water from thermodormant seeds inhibited the germination of non-dormant lettuce seeds. The inhibition was not an osmotic effect. Absorbance in the ultraviolet region was higher in germination water from thermodormant seeds than that of non-dormant seeds. It is concluded that inhibitors are involved in the induction of thermodormancy of lettuce seeds.

The known antagonistic effect of CO 2 on ethylene action and the fact that waterlogging leads to increased ethylene production in plants which apparently contributes to injury of submerged plants led us to suspect ethylene as a causative factor in soaking injury of seeds. This hypothesis was tested in the present study for Phaseolus vulgaris seeds by investigating the effect of the ethylene absorbant Hg(ClO 4 ) 2 and antagonists of ethylene production or action (AVG, NBD, Ag, Ni and Co) on soaking injury, the effect of ethylene and ethrel on soaking injury, and the effect of soaking on ethylene production

The mammalian testis expresses a class of small noncoding RNAs that interact with mammalian PIWI proteins. In mice, the PIWI-interacting RNAs (piRNAs) partner with mammalian PIWI proteins, PIWIL1 and PIWIL2, also known as MIWI and MILI, to maintain transposon silencing in the germline genome. Here, we demonstrate that inactivation of Nct1/2, two noncoding RNAs encoding piRNAs, leads to derepression of LINE-1 (L1) but does not affect mouse viability, spermatogenesis, testicular gene expression, or fertility. These findings indicate that piRNAs from a cluster on chromosome 2 are necessary to maintain transposon silencing.

Kinetin alleviates cycloheximide inhibition and oxygen alleviates chloramphenicol inibition of germination of lettuce seeds (Lactuca sativa L. cv Grand Rapids). The effect is not due to increased but rather a substitution for protein synthesis. A cytokinin and energy supply appear prime requirements for germination.

The capacity for protein synthesis in embryonic axes of Phaseolus vulgaris L. cv. Top Crop seeds was reduced markedly by soaking in airsaturated and CO2-saturated water. The former treatment induces soaking injury while the latter treatment prevents injury. After soaking, the capacity for protein synthesis in axes of seeds soaked in air-saturated water declined and the pattern of synthesis remained almost similar to that at the time of termination of soaking. However, the capacity and pattern of protein synthesis in axes of seeds soaked in CO2-saturated water recovered subsequent to soaking and approached that of non-soaked seeds.

In contrast to the seeds of other Cucurbitaceae species, cucumber seeds are able to germinate while completely submerged in water. Alcohol dehydrogenase activities of normoxic (control) and submerged seeds were similar. However, the ethanol content of submerged seeds was substantially higher than that of control seeds. Isocitrate lyase activity of the control seeds increased following radical protrusion while no increase in activity was observed in the submerged seeds after radicle protrusion. The rate of labelled carbon dioxide release from [1- 14 C]glucose, [6- 14 C]glucose,and [2- 14 C]acetate was lower in submerged than in control seeds. The oxygen uptake of seeds after 16 h of submersion was much lower than that of the control.

Erythrina caffra seeds were shown to be true anaerobic germinators. They exhibit a Pasteur effect, high alcohol dehydrogenase activity and produce high levels of ethanol under anoxia, in which situation germination starts to be suppressed by as little as 01% externally applied ethanol. Toxic levels of ethanol production appear to be prevented by a decrease in the rate of ethanol accumulation. Carbon monoxide does not inhibit germination. Cyanide, SHAM, iodoacetate, pyrazole, and 4-methylpyrazole are more inhibitory to anoxic than aerobic germination whereas azide, arsenate, and fluoride inhibit both. Azide, pyrazole, 4-methylpyrazole and a low concentration of cyanide and SHAM tend to stimulate ethanol production in air. At 10 mol m~3, 4-methylpyrazole stimulates anaerobic ethanol production. At higher concentrations this compound and all other inhibitors used suppress anaerobic ethanol production initially. Inhibition of ethanol production by 10 mol m~3 cyanide is paralleled by an accumulation of acetaldehyde. Azide and cyanide appear to exert their inhibitory effect at different loci.

Summary The germination of Citrullus lanatus seeds is inhibited by far-red-, red-, blue-, green- and white light. The inhibitory effect of light (with the exception of far-red) light is alleviated by a follow-up dark treatment. In addition it was found that the inhibitory effect of far-red light could not only be alleviated by a follow up red light treatment but also by short subsequent exposure to white- and blue light. The obtained results most probably indicate that germination is inhibited by red, blue, white, and, to a lesser extent, by green light due to pigment cycling between P r and P fr . During periods of pigment cycling much of the phytochrome probably accumulates in a form which can readily change to P fr in a follow up dark treatment. It appears that due to inherent differences in the P fr -threshold value necessary for germination, negatively- and positively photoblastic seeds cannot be made the same in their light requirements for germination merely by manipulating the phytochrome concentrations with light.

Summary Both the cytosolic and plastid PFK isoenzymes of cucumber are inhibited by sulphate at pH 7.2 but not at pH 8.0. Both the purine and pyrimidine triphosphates can be used as the phosphoryl donor to phosphorylate fructose 6-phosphate. Both isoenzymes exhibit lower Km-values for the pyrimidine triphosphates than purine triphosphates, while the maximum catalytic activity is higher with the purine triphosphates. The cytosolic PFK isoenzyme is not sensitive to GTP inhibition in contrast to the plastid isoenzyme where GTP is as inhibitory as ATP. Phosphoenol pyruvate and ADP are the strongest inhibitors of the plastid and cytosolic isoenzymes, respectively. Depending on the pH citrate, 2-phosphoglycerate, 3-phosphoglycerate and A TP also inhibit both isoenzymes. In most cases the inhibition caused by these compounds can be alleviated by the addition of phosphate. Fructose-2,6-bisphosphate has no effect on the activity of either isoenzymes in the presence and absence of the mentioned effectors.

White light completely inhibits the germination of Citrullus lanatus (Thunb.) Matsumara & Nakai seeds. Under these conditions light does not induce ribulose bisphosphate carboxylase (Rubisco) synthesis in the cotyledons. Although the seeds apparently are capable of attaining sufficient levels of the far-red light absorbing form of phytochrome, Pfr, in the dark to permit germination this does not induce Rubisco synthesis. However, it appears that a substantial amount of synthesis of the small subunit (SSU) takes place in the dark. The synthesis of the two subunits is therefore not tightly coordinated in this tissue, and in none of the treatments were equimolar concentrations of the two subunits present in the cotyledons. However, if the seeds are allowed to start germination in the dark and are then transferred to continuous light, Rubisco synthesis is induced. This induction of Rubisco synthesis in the cotyledons is dependent on the presence of the elongating radicle. Kinetin induces synthesis of Rubisco in isolated cotyledons in both the light and the dark, while 2-chloroethanephosphonic acid (Ethrel) only restores the sensitivity towards light activation of Rubisco synthesis. Synthesis of Rubisco in isolated cotyledons in the presence of these two compounds differs from that of the intact tissue in that the synthesis of the SSU is stimulated more than the synthesis of the large subunit (LSU).

The pyrophosphate : D-fructose-6-phosphate 1-phosphotranferase (PFP) from germinating Phaseolus vulgaris L. cv. Top Crop seeds was purified to a specific activity of 6.5 μmol(mg protein) −1 min −1. No difference in the pH-optimum for the forward and reverse reactions was found; activation of the enzyme by fructose-2,6-bisphosphate (fru-2,6-P2) did not affect the pH optimum. The concentration of fru-2,6-P2 needed for half activation (Kav) was 1.0 μM. Phosphate has a marked effect on the affinity of the enzyme for the activator, increasing the Kav-value to 2.0, 2.8 and 4.5 μM in the presence of 1.0, 5.0 and 10.0 mM Pi, respectively. The enzyme exhibits an absolute requirement for a divalent cation and exhibits Michaelis-Menton kinetics both in the presence and absence of fru-2,6-P2. The steady-state substrate interaction data and pattern of Pi inhibition (uncompetitive) towards PPi and mixed towards fructose-6-phosphate) suggests a mechanism involving a sequential ternary complex.