Return to sport and beyond following intramuscular tendon hamstring injury: A case report of an English Premier League football player.

BACKGROUND: Hamstring strain injuries are the most common type of injury in elite football and are associated with a high risk of reinjury, particularly those involving the intramuscular tendon (IMT). Limited information is available regarding the rehabilitation and return to sport (RTS) processes following such injuries. This case study describes the clinical presentation of an elite football player following IMT hamstring injury, their on- and off-pitch rehabilitation alongside performance monitoring throughout RTS and beyond. CASE SCENARIO: An elite football player suffered a grade 2c hamstring injury during an English Premier League (EPL) match. The player underwent early post-injury management, alongside progressive off-pitch physical preparation. The 'control-chaos continuum' was used as a framework for on-pitch rehabilitation to prepare the player for a return to full team training and competition. Objective and subjective markers of the player's response to progressive on- and off-pitch loading were monitored throughout RTS and beyond. OUTCOMES: The player returned to on-pitch rehabilitation after 11 days, to full team training having achieved weekly pre-injury chronic running load outputs after 35 days and played in the EPL 40 days post-injury. The player did not suffer reinjury for the rest of the EPL season. CONCLUSION: An understanding the unique structural and mechanical properties of the IMT, alongside expected RTS timeframes are important to inform rehabilitation and decision-making processes post-injury. Performance and frequent load-response monitoring throughout RTS and beyond, in conjunction with practitioner experience and effective communication are critical in facilitating effective RTS and reduce risk of reinjury following IMT injury.

Contextual considerations using the 'control-chaos continuum' for return to sport in elite football - Part 1: Load planning.

The 'control-chaos continnum' is an adaptable framework developed to guide the on-pitch rehabilitation process in elite football. One of the key objectives of the continuum is to progressively return players to their preinjury chronic running load, while incorporating the qualitative aspects of movement and cognitive stresses integral to competitive match-play. Whilst injury and player-specific considerations are key to an individualised rehabilitation approach, a host of contextual factors also play an important role in return to sport (RTS) planning. In this article, we highlight some key intrinsic and extrinsic contextual factors for the practitioner to consider in the RTS planning process to help mitigate reinjury risk upon a return to team training. While a return to chronic running load is generally a critical component of the framework, we highlight circumstances in elite football where it is a less relevant factor in RTS decision-making.

Prevalence of baseline HCV NS5A resistance associated substitutions in genotype 1a, 1b and 3 infection in Australia.

BACKGROUND: Direct-acting antivirals (DAA) have revolutionised hepatitis C virus (HCV) treatment, and most regimens include an NS5A inhibitor. Certain amino-acid substitutions confer resistance to NS5A inhibitors, termed resistance-associated substitutions (RAS). If present at baseline, they can reduce virological response rates. Population-based sequencing (PBS) is generally used for baseline sequencing, however next generation sequencing (NGS) reduces the threshold for detection of sequences encoding RAS from 20% to 5%. We determined the prevalence of NS5A RAS at baseline amongst Australian chronically infected with genotype (GT)1a, GT1b and GT3 HCV, using both PBS and NGS. METHODS: Samples from DAA-naïve individuals were received at the Victorian Infectious Disease Reference Laboratory between June 2016 and December 2018. All samples were analysed for NS5A RAS using PBS. A subset of GT1 HCV samples were processed using NGS technology (Vela Diagnostics, Singapore) to determine the improvement in sensitivity. RESULTS: In total, 672 samples were analysed using PBS. The baseline prevalence of NS5A RAS was 7.6% for GT1a (n = 25/329), 15.7% for GT1b (n = 8/51) and 15.1% for GT3 (n = 44/292). NGS only marginally increased sensitivity for NS5A RAS at baseline in GT1a (16% vs 17%) and GT1b (29% vs 36%). CONCLUSION: The prevalence of NS5A RAS in GT1a HCV in Australia was low compared with international data, and was similar to other reported international prevalence for GT1b and GT3 infection. NGS at baseline only marginally increased sensitivity for the detection of NS5A RAS in patients with GT1 HCV and cannot be recommended for routine use at baseline in clinical practice.

Evaluation of two commercial, rapid, ELISA kits testing for scrapie in retro-pharyngeal lymph nodes in sheep.

AIMS: To estimate the number of cases of scrapie that would occur in sheep of different prion protein (PrP) genotypes if scrapie was to become established in New Zealand, and to compare the performance of two commercially available, rapid ELISA kits using ovine retro-pharyngeal lymph nodes (RLN) from non-infected and infected sheep of different PrP genotypes. METHODS: Using published data on the distribution of PrP genotypes within the New Zealand sheep flock and the prevalence of cases of scrapie in these genotypes in the United Kingdom, the annual expected number of cases of scrapie per genotype was estimated, should scrapie become established in New Zealand, assuming a total population of 28 million sheep. A non-infected panel of RLN was collected from 737 sheep from New Zealand that had been culled, found in extremis or died. Brain stem samples were also collected from 131 of these sheep. A second panel of infected samples comprised 218 and 117 RLN from confirmed scrapie cases that had originated in Europe and the United States of America, respectively. All samples were screened using two commercial, rapid, transmissible spongiform encephalopathy ELISA kits: Bio-Rad TeSeE ELISA (ELISA-BR), and IDEXX HerdChek BSE-Scrapie AG Test (ELISA-ID). RESULTS: If scrapie became established in New Zealand, an estimated 596 cases would occur per year; of these 234 (39%) and 271 (46%) would be in sheep carrying ARQ/ARQ and ARQ/VRQ PrP genotypes, respectively. For the non-infected samples from New Zealand the diagnostic specificity of both ELISA kits was 100%. When considering all infected samples, the diagnostic sensitivity was 70.4 (95% CI=65.3-75.3)% for ELISA-BR and 91.6 (95% CI=88.2-94.4)% for ELISA-ID. For the ARQ/ARQ genotype (n=195), sensitivity was 66.2% for ELISA-BR and 90.8% for ELISA-ID, and for the ARQ/VRQ genotype (n=107), sensitivity was 81.3% for ELISA-BR and 98.1% for ELISA-ID. CONCLUSIONS: In this study, the ELISA-ID kit demonstrated a higher diagnostic sensitivity for detecting scrapie in samples of RLN from sheep carrying scrapie-susceptible PrP genotypes than the ELISA-BR kit at comparable diagnostic specificity. CLINICAL RELEVANCE: The diagnostic performance of the ELISA-ID kit using ovine RLN merits the consideration of including this assay in the national scrapie surveillance programme in New Zealand.

Polychlorinated biphenyl concentrations of burbot Lota lota from Great Slave Lake are very low but vary by sex.

Total polychlorinated biphenyl concentrations (ΣPCBs) in whole fish were determined for 18 ripe female burbot Lota lota and 14 ripe male burbot from Great Slave Lake, a lake with no known point sources of PCBs. In addition, ΣPCBs were determined in both somatic tissue and gonads for a randomly selected subset of 5 females and 5 males. Mean ΣPCBs for females and males were 2.89 and 3.76 ng/g, respectively. Thus, males had 30 % greater ΣPCBs than females. Based on ΣPCB determinations for somatic tissue and gonads, ΣPCBs of females and males would be expected to decrease by 18 % and increase by 6 %, respectively, immediately after spawning due to the release of gametes. Results from a previous study in eastern Lake Erie indicated that males had 28 and 71 % greater ΣPCBs than females from populations of younger (ages 6-13 years) and older (ages 14-17 years) burbot, respectively. Thus, although younger burbot from Lake Erie had approximately 50 times greater ΣPCBs than Great Slave Lake burbot, the relative difference in ΣPCBs between the sexes was remarkably similar across both populations. Our results supported the contention that the widening of the difference in ΣPCBs between the sexes in older burbot from Lake Erie was attributable to a "hot spot" effect operating on older burbot because Lake Erie has received PCB point source loadings. Our results also supported the contention that male fish expend energy at a rate between 15 and 30 % greater than females. Eventually, these results will be useful in developing sex-specific bioenergetics models for fish.

Is statin-induced diabetes clinically relevant? A comprehensive review of the literature.

In those predisposed to the development of diabetes (the insulin resistant, obese and older patients) statins may increase the risk of developing diabetes. Despite the fact that the conversion to diabetes is generated from post hoc analyses, it seems to be a class effect with a dose-response relationship. However, statins have not been clearly shown to increase diabetic microvascular complications (retinopathy, nephropathy and neuropathy). Thus, the clinical significance of increased glucose levels in patients treated on statins is uncertain. While the exact mechanism for how statins increase the risk of diabetes is unknown, a possible explanation is through a reduction in adiponectin levels. Despite the fact that higher statin doses are more likely to lead to new-onset diabetes, for every case of diabetes caused, there are approximately three cardiovascular events reduced with high dose versus moderate dose statin therapy. Overall, the small risk of developing type 2 diabetes with statin therapy is far outweighed by the potential of statins to decrease cardiac events.

Polychlorinated biphenyl concentrations and activity of sea lamprey Petromyzon marinus vary by sex.

We determined the polychlorinated biphenyl (PCB) concentrations of 40 male and 40 female adult sea lampreys Petromyzon marinus captured in the Cheboygan River, a tributary to Lake Huron, during May 2011. In addition, we performed a laboratory experiment using passive integrated transponder tags to determine whether male adult sea lampreys were more active than female adult sea lampreys. Sex had a significant effect on PCB concentration, and PCB concentration at a given level of sea lamprey condition was approximately 25 % greater in males than in females. Adjusting for the difference in condition between the sexes, males averaged a 17 % greater PCB concentration compared with females. Results from the laboratory experiment indicated that males were significantly more active than females. The observed sex difference in PCB concentrations was not due to female sea lampreys releasing eggs at spawning because the sea lamprey is semelparous, and we caught the sea lampreys before spawning. Rather, we attributed the sex difference in PCB concentrations to a greater rate of energy expenditure in males compared with females. We proposed that this greater rate of energy expenditure was likely due to greater activity. Our laboratory experiment results supported this hypothesis. A greater resting metabolic rate may also have contributed to a greater rate of energy expenditure. Our findings should eventually be applicable toward improving control of sea lamprey, a pest responsible for considerable damage to fisheries in lakes where it is not native.

Sex difference in polychlorinated biphenyl concentrations of burbot Lota lota from Lake Erie.

Whole-fish polychlorinated biphenyl (PCB) concentrations were determined for 25 female and 25 male burbot Lota lota from Lake Erie. Bioenergetics modeling was used to investigate whether the sex difference in growth rate resulted in a difference in gross growth efficiency (GGE) between the sexes. For ages 6-13 years, male burbot averaged 28 % greater PCB concentrations than female burbot. The sex difference in PCB concentrations widened for ages 14-17 years, with male burbot having, on average, 71 % greater PCB concentrations than female burbot. Bioenergetics modeling results showed that the faster growth rate exhibited by female burbot did not lead to greater GGE in female individuals of the younger burbot and that the faster growth by female fish led to female GGE being only 2 % greater than male GGE in older burbot. Although our bioenergetics modeling could not explain the observed sex difference in PCB concentrations, we concluded that a sex difference in GGE was the most plausible explanation for the sex difference in PCB concentrations of burbot ages 6-13 years. Not only are male fish likely to be more active than female fish, but the resting metabolic rate of male fish may be greater than that of female fish. We also concluded that the widening of the sex difference in PCB concentrations for the older burbot may be due to many of the older male burbot spending a substantial amount of time in the vicinity of mouths of rivers contaminated with PCBs.

Therapies for diabetic dyslipidaemia.

Correction of diabetic dyslipidaemia in diabetic patients is the most important factor in reducing cardiac risk. Diabetic dyslipidaemia is characterized by elevated triglycerides, low total high-density lipoprotein (HDL) and small dense low-density lipoprotein (LDL) particles. The most important therapeutic goal in diabetic dyslipidaemia is correction of the non-HDL-cholesterol (HDL-C) level. Glycaemic control with particular attention to postprandial glucose control plays a role not only in improving dyslipidaemia but also in lowering cardiac events. Pioglitazone is particularly effective for improving the manifestations of diabetic dyslipidaemia, in addition to its favorable effects on systemic inflammation and hyperglycaemia. Use of statins in addition to lifestyle change is recommended in most if not all type 2 diabetic patients and the goal should be to lower the LDL to a level recommended for the patient with existing cardiovascular disease (CVD) (non-HDL-C level <100 mg/dl). In addition, therapies for normalization of HDL and triglyceride levels should be deployed. Most patients with type 2 diabetes (T2D) will require combining a lipid-lowering therapy with therapeutic lifestyle changes to achieve optimal lipid levels. Combinations usually include two or more of the following: a statin, nicotinic acid, omega-3 fats and bile acid sequestrants (BASs). Fibrates may also be of use in diabetic patients with persistently elevated triglycerides and depressed HDL-C levels, although their role in lowering adverse CV events is questionable.

A cross-sectional survey of influenza A infection and management practices in small rural backyard poultry flocks in New Zealand.

AIM: To obtain baseline data on the management of small non-commercial backyard poultry flocks, in two rural regions of New Zealand, to investigate potential transmission pathways for avian influenza (AI), and to investigate the presence of AI in these flocks. METHODS: During August-October 2006 a questionnaire was sent to 105 farms in the Bay of Plenty and Wairarapa with poultry flocks comprising fewer than 50 chickens, located near wetlands where AI virus had been detected previously in wild ducks. Information was collected on the number and species of poultry reared, opportunities for interaction between wild birds and poultry, farm biosecurity measures, and health status of poultry. Between September and November 2006, blood and tracheal/cloacal swabs were collected from poultry on a subset of 12 high-risk farms in each location. Influenza A-specific antibodies in sera were assayed using ELISA, and positive sera were further tested for the presence of H5 and H7 subtype-specific antibodies, using haemagglutination inhibition (HI) assay. The presence of influenza A virus in swabs was detected using real-time reverse transcriptase-PCR (RRT-PCR). RESULTS: Returned questionnaires were received from 54 farms. Overall, 80% had only chickens, 13% chickens and ducks, and 7% had chickens and other galliform species. Nearly all (96%) kept backyard chickens for personal consumption of eggs, with a small proportion (19%) preparing birds for the table. On surveyed farms wild waterfowl were seen on pastures (70%) and/or farm waterways (46%). Waterfowl were recorded as visiting areas where domestic birds were kept on 31% of farms. Bird litter and manure were composted (94%) or buried (6%) on-farm, as were most (82%) dead birds. During the targeted cross-sectional survey of 24 farms clinical disease was not recorded in any poultry flock. Of 309 chicken sera tested, 11 (3.6%) from five farms across both regions tested positive for influenza A antibodies. In contrast, 16/54 (30%) duck sera from three farms in the Wairarapa were positive. Avian influenza H5 and H7 subtype-specific antibodies were excluded in ELISA positive sera using HI testing, and influenza A virus was not detected using RRT-PCR. CONCLUSIONS: The study confirmed that small backyard poultry flocks located near waterfowl habitats were exposed to non-notifiable low-pathogenic AI viruses. Findings indicate a number of potential risk pathways for the transmission of AI viruses between wild birds and non-commercial poultry, and hence the need for continued surveillance for AI in backyard flocks and wild birds in New Zealand.

Comparison of the Q-fever complement fixation test and two commercial enzyme-linked immunosorbent assays for the detection of serum antibodies against Coxiella burnetti (Q-fever) in ruminants : recommendations for use of serological tests on imported animals in New Zealand.

AIM: To make valid recommendations on the use of serological test methods for the detection of serum antibodies in ruminants against Coxiella burnetii (Q-fever), by comparing the performance of the complement fixation test (CFT) and two ELISA, and by identifying reasons for discrepancies between the test methods. METHODS: A total of 73 serum samples from infected cattle, 69 from infected goats, and 100 samples from non-infected cattle and 57 samples from non-infected sheep, as well as 95 samples from infected cattle herds (mix of seropositive and seronegative samples), were tested using the CFT, the IDEXX ELISA (I-ELISA) and the Pourquier ELISA (P-ELISA). A mixed panel of 12 serum samples from sheep from inter-laboratory proficiency testing (proficiency panel) was also tested using the CFT and both ELISA, and further investigated using IgG- and IgM-specific ELISA. RESULTS: Generally, the two commercial ELISA were more sensitive than the CFT for the detection of infected ruminants. Good agreement between ELISA for positive and negative results was found for samples from the infected herd, while results for the positive panels varied between the two ELISA. For the total of the positive serum panels, the I-ELISA detected 95% of samples as positive or suspicious, while the P-ELISA detected only 81%. In the P-ELISA, more samples were considered suspicious (18%) than in the I-ELISA (14%). All sera from non-infected sheep and cattle tested negative in the serological test methods employed, except for one positive sample from a sheep in the P-ELISA. Further investigation revealed that a CFT-positive but ELISA-negative result was due to high IgM and low IgG reactivity. CONCLUSIONS: The two commercial ELISA were more sensitive than the CFT in all panels from infected ruminants. However, they could only detect IgG. The I-ELISA should be the serological test method of choice for cattle, sheep and goats for import testing of animals into New Zealand because it was more sensitive than the P-ELISA and was equally specific to the PELISA and the CFT. For other animal species, such as deer and camelids, the CFT should still be used since none of the ELISA has been evaluated for these species. This study has shown that the two commercial ELISA will detect the majority of infected ruminants but may miss animals that have not developed an IgG response.

Grid cells and theta as oscillatory interference: electrophysiological data from freely moving rats.

The oscillatory interference model (Burgess et al. (2007) Hippocampus 17:801-812) explains the generation of spatially stable, regular firing patterns by medial entorhinal cortical (mEC) grid cells in terms of the interference between velocity-controlled oscillators (VCOs) with different preferred directions. This model predicts specific relationships between the intrinsic firing frequency and spatial scale of grid cell firing, the EEG theta frequency, and running speed (Burgess,2008). Here, we use spectral analyses of EEG and of spike autocorrelograms to estimate the intrinsic firing frequency of grid cells, and the concurrent theta frequency, in mEC Layer II in freely moving rats. The intrinsic firing frequency of grid cells increased with running speed and decreased with grid scale, according to the quantitative prediction of the model. Similarly, theta frequency increased with running speed, which was also predicted by the model. An alternative Moiré interference model (Blair et al.,2007) predicts a direction-dependent variation in intrinsic firing frequency, which was not found. Our results suggest that interference between VCOs generates the spatial firing patterns of entorhinal grid cells according to the oscillatory interference model. They also provide specific constraints on this model of grid cell firing and have more general implications for viewing neuronal processing in terms of interfering oscillatory processes.

Specificity of non-structural protein enzyme-linked immunosorbent assays for the detection of serum antibodies against foot-and-mouth disease virus in a target population in New Zealand.

AIMS: To determine the diagnostic specificities of two commercial screening ELISA, the Bommeli/IDEXX Chekit FMD 3ABC indirect ELISA (ELISA-1) and the Ceditest FMDV NS blocking ELISA (ELISA-2), for foot-and-mouth disease (FMD) in cattle, sheep and pigs in New Zealand, and to compare them with other published studies. To consider the implications for FMD surveillance of using two ELISA in series, a consideration arising from the absence of a gold standard virus neutralisation test (VNT) in New Zealand. METHODS: Serum samples from non-infected cattle (n=1,015), sheep (n=1,185), and pigs (n=233) from New Zealand were tested in ELISA-1 and ELISA-2 for the detection of serum antibodies against non-structural proteins of the FMD virus. The ELISA were performed according to the manufacturers' instructions. RESULTS: The diagnostic specificities for ELISA-1 for cattle, sheep and pigs were 99.9%, 99.7% and 99.6%, respectively, and for ELISA-2 were 99.5%, 99.7% and 99.6%, respectively. False-positive reactors in one ELISA were negative in the other ELISA, and vice versa. Using the diagnostic sensitivity data taken from international studies and the diagnostic specificities calculated in this study resulted in overall specificities of 100% in cattle and sheep using serial test interpretation, and 99.2% and 99.0%, respectively, using parallel test interpretation. Diagnostic sensitivities available in the literature varied considerably, and the associated overall serial sensitivity could be as low as 78.7% in cattle and 33.2% in sheep. CONCLUSIONS: Diagnostic specificities for both ELISA for the target population were comparable with those obtained in livestock populations elsewhere. In surveillance to re-establish New Zealand's freedom from FMD, the use of two ELISA in series would improve the overall specificity in individual animals. However, care would be required to ensure that herd sensitivity was sufficient to detect infection.

A real-time polymerase chain reaction assay for the detection of Mycoplasma agalactiae.

AIM: To develop a real-time PCR for the detection of Mycoplasma agalactiae, using PCR primers targeting the ma-mp81 gene. METHODS: A group of 15 M. agalactiae isolates, 21 other Mycoplasma spp. isolates and 21 other bacterial isolates was used in evaluation of the assay. RESULTS: All M. agalactiae isolates were detected by the assay and none of the non-target isolates was amplified. The analytical detection limit of the assay was 10 fg of purified genomic DNA and 104 cfu/ml milk inoculated with M. agalactiae. When applied to goat-milk samples collected from three herds free of M. agalactiae infection, the assay had a specificity of 100%. CONCLUSIONS: The assay would be useful in a diagnostic laboratory, providing specific, sensitive and rapid detection of M. agalactiae.

Infection trials in pigs with a human isolate of Brucella ( isolate 02/611 'marine mammal type' ).

AIM: To determine if pigs could support infection of a human Brucella isolate (Brucella 02/611) from New Zealand, and to study seroconversion to this isolate using a competitive ELISA. METHODS: Ten weaner piglets were challenged with 4.8 x 10(8) cfu of organisms by the oral and ocular routes. Culture was attempted on blood samples taken prior to challenge, and 4, 7, 9, 11, 14, 21 and 28 days post-challenge, and on tissue samples taken at the termination of the trial, 1 month after challenge. Sera were analysed for antibody using an ELISA. For reference comparison, similar trials were conducted in two pigs using an isolate of Brucella suis biovar 1, and two pigs using an isolate of B. suis biovar 3. RESULTS: Brucella 02/611 organisms were re-isolated from one lymph node each from three pigs; all other samples were negative. Low and transient antibody titres were detected using a competitive ELISA in three pigs, two of which were culture negative. Organisms of B. suis reference strains were re-isolated from multiple samples from each of the four animals. CONCLUSION: Brucella 02/611 does not seem to replicate readily in pigs. It is unlikely that pigs were the original maintenance hosts for Brucella 02/611.

Real-time polymerase chain reaction assays for the detection of members of the Mycoplasma mycoides cluster.

AIM: To develop real-time PCR assays for the detection and differentiation of members of the Mycoplasma mycoides cluster. METHODS: Five real-time PCR assays were designed to allow differentiation of members of the M. mycoides cluster: an assay for detection of the M. mycoides subspecies, viz M. mycoides subsp mycoides large colony (MmmLC), M. mycoides subsp capri (Mmc), and M. mycoides subsp mycoides small colony (MmmSC); one for the detection of the M. capricolum subspecies, viz M. capricolum subsp capricolum (Mcc), M. capricolum subsp capripneumoniae (Mccp), and Mycoplasma sp bovine group 7 (BG7); and three for the specific detection of MmmSC, Mccp, and BG7. A panel of 74 Mycoplasma isolates from various geographical origins and a panel of 21 other bacterial isolates were used to evaluate the sensitivity and specificity of the assays. RESULTS: The assays displayed 100% analytical sensitivity in detecting all target Mycoplasma isolates. The analytical detection limit for the assays to detect the M. mycoides subspecies, M. capricolum subspecies, and MmmSC was determined to be 100 fg of genomic DNA, while the Mccp and BG7 assays had a detection limit of 100 fg and 10 fg of genomic DNA, respectively. The M. mycoides subspecies assay had a detection limit of 10(3) (SD 10(2)) cfu/ml milk, 10(4) (SD 10(4)) cfu per swab, and 10(3) (SD 10(3)) cfu/g lung in inoculated samples. The assays displayed 100% specificity when applied to non-target bacterial isolates and to 110 culture-negative milk samples. CONCLUSIONS: The assays were highly sensitive and specific, and provide accurate detection and differentiation of the members of the M. mycoides cluster.

Environmental novelty is signaled by reduction of the hippocampal theta frequency.

The hippocampal formation (HF) plays a key role in novelty detection, but the mechanisms remain unknown. Novelty detection aids the encoding of new information into memory-a process thought to depend on the HF and to be modulated by the theta rhythm of EEG. We examined EEG recorded in the HF of rats foraging for food within a novel environment, as it became familiar over the next five days, and in two more novel environments unexpectedly experienced in trials interspersed with familiar trials over three further days. We found that environmental novelty produces a sharp reduction in the theta frequency of foraging rats, that this reduction is greater for an unexpected environment than for a completely novel one, and that it slowly disappears with increasing familiarity. These results do not reflect changes in running speed and suggest that the septo-hippocampal system signals unexpected environmental change via a reduction in theta frequency. In addition, they provide evidence in support of a cholinergically mediated mechanism for novelty detection, have important implications for our understanding of oscillatory coding within memory and for the interpretation of event-related potentials, and provide indirect support for the oscillatory interference model of grid cell firing in medial entorhinal cortex.