Surgical challenges of giant parathyroid adenomas weighing 10 g or more.

PURPOSE: An average parathyroid adenoma (PA) weighs < 1 g. This study aimed to characterise giant PAs ≥ 10 g (GPAs) to facilitate surgical management of primary hyperparathyroidism (PHPT). METHODS: All patients with a GPA confirmed on histology were recruited from the Monash University Endocrine Surgery Unit database. Clinical and demographic data were collected and compared to a group of non-GPA patients. RESULTS: A total of 14 GPAs were identified between 2007 and 2018 out of 863 patients (1.6%) with a single PA excised for PHPT. The GPA patients were compared to a control group of 849 non-GPA patients in the same period with similar mean age (62 ± 16 vs 63 ± 14, P = 0.66) and gender distribution (64% vs 75% female, P = 0.35). Pre-operative calcium (Ca) and parathyroid hormone (PTH) levels were significantly higher in GPA patients (P < 0.001). A higher percentage of GPA patients (79%) had concordant localisation studies (ultrasound and sestamibi) than control patients (59%), (P = 0.13), but they were significantly less likely to undergo MIP (55% vs 82%, P = 0.02). The median GPA weighed 12.5 g (IQR 10.5-24.3). Median serum Ca normalised by day 1 post-operatively, while PTH remained elevated. Both serum Ca and PTH levels were in the normal range at 3 months. All GPA lesions were benign on histopathology. CONCLUSION: GPAs are rare and display severe clinical and biochemical abnormalities. Despite their large size, concordant pre-operative imaging was not always achieved, and a few patients were suitable for MIP.

Neurodevelopmental scaling is a major driver of brain-behavior differences in temperament across dog breeds.

Behavioral traits like aggression, anxiety, and trainability differ significantly across dog breeds and are highly heritable. However, the neural bases of these differences are unknown. Here we analyzed structural MRI scans of 62 dogs in relation to breed-average scores for the 14 major dimensions in the Canine Behavioral Assessment and Research Questionnaire, a well-validated measure of canine temperament. Several behavior categories showed significant relationships with morphologically covarying gray matter networks and regional volume changes. Networks involved in social processing and the flight-or-fight response were associated with stranger-directed fear and aggression, putatively the main behaviors under selection pressure during wolf-to-dog domestication. Trainability was significantly associated with expansion in broad regions of cortex, while fear, aggression, and other "problem" behaviors were associated with expansion in distributed subcortical regions. These results closely overlapped with regional volume changes with total brain size, in striking correspondence with models of developmental constraint on brain evolution. This suggests that the established link between dog body size and behavior is due at least in part to disproportionate enlargement of later-developing regions in larger brained dogs. We discuss how this may explain the known correlation of increasing reactivity with decreasing body size in dogs.

Severe hyperkalaemia complicating parathyroidectomy in patients with end-stage renal disease.

We evaluated the incidence of perioperative hyperkalaemia in end-stage renal disease (ESRD) patients undergoing parathyroidectomy and investigated possible contributors to this phenomenon. This was a retrospective cohort study looking at patients who had undergone parathyroidectomy for chronic kidney disease-associated mineral bone disease (CKD-MBD) at The Alfred Hospital, Melbourne, since 2001. Baseline demographics including age, gender, aetiology of renal failure and mode of renal replacement therapy as well as anaesthetic technique and duration of surgery were studied as possible contributors. Perioperative potassium values were compared to preoperative baseline. Following stratification into normokalaemic and hyperkalaemic groups, demographic and operative data were compared. Twenty-two patients met the inclusion criteria with a median (interquartile range, IQR) age of 48.5 (42-59) years. There was a male predominance of 68%. The median (IQR) surgical time was 131 (115-164) minutes. Potassium levels rose perioperatively, with a 27.3% incidence of perioperative hyperkalaemia. Median duration of surgery was longer in the hyperkalaemic patients (167 minutes versus 125 minutes). Following the withdrawal of cinacalcet, parathyroidectomy is increasingly required in ESRD patients with CKD-MBD. Potentially life-threatening hyperkalaemia poses a significant risk in the perioperative period. Serial electrolyte monitoring is crucial to safety in this patient group. A multidisciplinary approach to perioperative management is required to ensure optimal timing of renal replacement therapy and appropriate means of serial blood sampling.

Why do people buy dogs with potential welfare problems related to extreme conformation and inherited disease? A representative study of Danish owners of four small dog breeds.

A number of dog breeds suffer from welfare problems due to extreme phenotypes and high levels of inherited diseases but the popularity of such breeds is not declining. Using a survey of owners of two popular breeds with extreme physical features (French Bulldog and Chihuahua), one with a high load of inherited diseases not directly related to conformation (Cavalier King Charles Spaniel), and one representing the same size range but without extreme conformation and with the same level of disease as the overall dog population (Cairn Terrier), we investigated this seeming paradox. We examined planning and motivational factors behind acquisition of the dogs, and whether levels of experienced health and behavior problems were associated with the quality of the owner-dog relationship and the intention to re-procure a dog of the same breed. Owners of each of the four breeds (750/breed) were randomly drawn from a nationwide Danish dog registry and invited to participate. Of these, 911 responded, giving a final sample of 846. There were clear differences between owners of the four breeds with respect to degree of planning prior to purchase, with owners of Chihuahuas exhibiting less. Motivations behind choice of dog were also different. Health and other breed attributes were more important to owners of Cairn Terriers, whereas the dog's personality was reported to be more important for owners of French Bulldogs and Cavalier King Charles Spaniels but less important for Chihuahua owners. Higher levels of health and behavior problems were positively associated with a closer owner-dog relationship for owners of Cavalier King Charles Spaniels and Chihuahuas but, for owners of French Bulldogs, high levels of problems were negatively associated with an intention to procure the same breed again. In light of these findings, it appears less paradoxical that people continue to buy dogs with welfare problems.

Effects of surgical and chemical sterilization on the behavior of free-roaming male dogs in Puerto Natales, Chile.

Population management of free-roaming domestic dogs (Canis lupus familiaris) is of interest due to the threat these animals pose to people, other animals and the environment. Current sterilization procedures for male dogs include surgical and chemical methods. However, little is known about how these procedures affect their behavior. The primary objective of this study was to investigate changes in selected behaviors following chemical and surgical sterilization in a male free-roaming dog (FRD) population in southern Chile. We also examined the association between serum testosterone levels and behaviors thought to be influenced by circulating androgens. A total of 174 dogs were randomly assigned to either a surgical or chemical sterilization group, or a control group. At the onset of the intervention period, 119 dogs remained and 102 dogs successfully completed the study. Each dog was monitored pre- and post-intervention using video recordings, GPS collars, and blood samples for the measurement of testosterone. Analysis of behavior revealed that surgically castrated dogs showed no reduction of sexual activity or aggression when compared to their pre-intervention behavior. Chemically sterilized dogs showed a statistically significant increase in dog-directed aggression, but no change in sexual activity. There was no change in home range size in any groups between the pre- and post-intervention measurement. We found no consistent association between levels of serum testosterone concentration and behavioral changes in any of the groups. This study presents the first detailed behavioral observations following surgical and chemical sterilization in male FRDs. The information generated is highly relevant to communities struggling with the control of FRDs. Complementary studies to further our understanding of the effects of male sterilization on the behavioral and reproductive dynamics of FRD populations are needed.

The effect of routine reversal of neuromuscular blockade on adequacy of recurrent laryngeal nerve stimulation during thyroid surgery.

Testing of the integrity of the recurrent laryngeal nerve during thyroid surgery has become routine practice for many surgeons to aid dissection and minimise the chance of inadvertent nerve injury. We hypothesised that routine reversal of an intermediate-acting, non-depolarising neuromuscular blocking agent would improve conditions for stimulation of the recurrent laryngeal nerve. We conducted a single-centre, randomised, double-blind placebo-controlled trial of patients undergoing thyroid surgery by the same surgeon. After randomisation, the participants received either neostigmine 2.5 mg with glycopyrrolate 0.4 mg or placebo, at 30 minutes after induction of anaesthesia and administration of 0.4 mg/kg of atracurium. The primary outcome was the subjective assessment by the surgeon as to whether the neuromuscular function was adequate for stimulation of the recurrent laryngeal nerve using a neuromuscular integrity monitor (NIM). Time to NIM stimulation was 44.6 minutes in the placebo group and 41.4 minutes in the intervention group (P=0.268). Of the 21 patients who received the neuromuscular blockade reversal, 20 (95.2%) had adequate surgical conditions for NIM stimulation, compared to 9 out of 18 patients (50%) in the placebo group (P=0.002). Three of the ten patients (30%) with inadequate reversal showed no evidence of residual blockade assessed peripherally. The routine reversal of neuromuscular blockade at 30 minutes post induction appears to result in adequate surgical conditions for safe stimulation of the recurrent laryngeal nerve. Return of neuromuscular function at a peripheral site does not guarantee adequate laryngeal muscle function for use of the NIM.

Changes in blood testosterone concentrations after surgical and chemical sterilization of male free-roaming dogs in southern Chile.

There is a growing interest in chemical sterilization as an alternative to surgical castration in large-scale sterilization campaigns to control canine populations. An important step toward understanding the short-term and long-term effects of chemical sterilants is to determine their impact on blood testosterone concentrations, particularly as these could influence dog behavior after treatment. A field trial was conducted with 118 free-roaming male dogs in the Chilean Patagonia, where 36 dogs were chemically sterilized using EsterilSol, 39 dogs were surgically castrated, and 43 dogs remained intact as controls. Blood testosterone levels were determined at four time periods: on enrollment 6 months before treatment (t-6m), at the time of treatment (t0, within one hour after surgical castration or chemical sterilization and during a concurrent 2-week period for the control group), four (t+4m), and six (t+6m) months after treatment. Intrinsic and temporal factors were evaluated; age was significantly associated with testosterone, where dogs 2- to 4-year-old had the highest testosterone concentrations (P = 0.036), whereas body weight and body condition scores were not associated with testosterone; testosterone concentration was not influenced by time of day, month, or season. After treatment (t+4m and t+6m), all of the surgically castrated dogs had testosterone concentrations below 1.0 ng/mL. On the basis of this cut point (<1 ng/mL), testosterone remained unchanged in 66% of the chemically sterilized dogs at both t+4m and t+6m; it remained low for 22% of dogs at both t+4m and t+6m; it was unchanged at t+4m but low at t+6m in 9% of dogs; and, it was low at t+4m but reverted back to unchanged at t+6m in one dog (3%). Incidentally, testosterone in chemically sterilized dogs increased dramatically within 1 hour of treatment (t0), more than doubling (131%) the concentration of control dogs at the time of treatment (t0), likely because of severe necrosis of interstitial cells. The use of EsterilSol as a method of sterilizing dogs had a variable effect on blood testosterone concentrations. Approximately, 30% of chemically sterilized dogs had a reduced testosterone concentration (actual maximum, 1 ng/mL) after 6 months, similar to that of surgically castrated dogs. Most chemically sterilized dogs, however, showed no long-term changes in blood testosterone concentrations.

A cohort and database study of airway management in patients undergoing thyroidectomy for retrosternal goitre.

Patients undergoing thyroid surgery with retrosternal goitre may raise concerns for the anaesthetist, especially airway management. We reviewed a multicentre prospective thyroid surgery database and extracted data for those patients with retrosternal goitre. Additionally, we reviewed the anaesthetic charts of patients with retrosternal goitre at our institution to identify the anaesthetic induction technique and airway management. Of 4572 patients in the database, 919 (20%) had a retrosternal goitre. Two cases of early postoperative tracheomalacia were reported, one in the retrosternal group. Despite some very large goitres, no patient required tracheostomy or cardiopulmonary bypass and there were no perioperative deaths. In the subset of 133 patients managed at our institution over six years, there were no major adverse anaesthetic outcomes and no patient had a failed airway or tracheomalacia. In the latter cohort, of 32 (24%) patients identified as having a potentially difficult airway, 17 underwent awake fibreoptic tracheal intubation, but two of these were abandoned and converted to intravenous induction and general anaesthesia. Eleven had inhalational induction; two of these were also abandoned and converted to intravenous induction and general anaesthesia. Of those suspected as having a difficult airway, 28 (87.5%) subsequently had direct laryngoscopy where the laryngeal inlet was clearly visible. We found no good evidence that thyroid surgery patients with retrosternal goitre, with or without symptoms and signs of tracheal compression, present the experienced anaesthetist with an airway that cannot be managed using conventional techniques. This does not preclude the need for multidisciplinary discussion and planning.

Enhanced recovery after surgery program for elective abdominal surgery at three Victorian hospitals.

The aim of this study was to evaluate the anaesthesia care of an enhanced recovery after surgery (ERAS) program for patients having abdominal surgical in Victorian hospitals. The main outcome measure was the number of ERAS items implemented following introduction of the ERAS program. Secondary endpoints included process of care measures, outcomes and hospital stay. We used a before-and-after design; the control group was a prospective cohort (n=154) representing pre-existing practice for elective abdominal surgical patients from July 2009. The introduction of a comprehensive ERAS program took place over two months and included the education of surgeons, anaesthetists, nurses and allied health professionals. A post-implementation cohort (n=169) was enrolled in early 2010. From a total of 14 ERAS-recommended items, there were significantly more implemented in the post-ERAS period, median 8 (interquartile range 7 to 9) vs 9 (8 to 10), P <0.0001. There were, however, persistent low rates of intravenous fluid restriction (25%) and early removal of urinary catheter (31%) in the post-ERAS period. ERAS patients had less pain and faster recovery parameters, and this was associated with a reduced hospital stay, geometric mean (SD) 5.7 (2.5) vs 7.4 (2.1) days, P=0.006. We found that perioperative anaesthesia practices can be readily modified to incorporate an enhanced recovery program in Victorian hospitals.

Free-roaming dog control among OIE-member countries.

A questionnaire was distributed to the state veterinary services of all 172 OIE countries to collect data on the different national approaches to dog population control. We used all 81 completed questionnaires with ≥80% of the question answered to identify the different national approaches to the issue. The intensity of the free-roaming dog (FRD) problem was negatively correlated with the value of the UN's human development index recognized for each country. Dog bites/attacks and rabies were the main problems associated with FRDs, and these problems were reported disproportionately by less-developed countries. Dog-control programs (DCP) were more widely used among the more-developed countries. In less-developed countries, DCPs (when they existed at all) tended to employ killing methods (including poisoned baits), that are not recommended on animal-welfare grounds.

Development and validation of a novel method for evaluating behavior and temperament in guide dogs.

Most guide and service dog organizations would benefit from the development of accurate methods for the early evaluation of canine temperament traits. This paper describes the development and validation of a novel questionnaire method for assessing behavior and temperament in 1-year-old guide dogs. Volunteer puppy-raisers scored a total of 1097 prospective guide dogs on a series of 40 semantic differential-type, behavioral rating scales. Principle components factor analysis of these scores extracted eight stable and interpretable common factors: stranger-directed fear/aggression, non-social fear, energy level, owner-directed aggression, chasing, trainability, attachment, and dog-directed fear/aggression. Three of these eight factors exhibited moderate internal consistency (Cronbach's alpha>/=0.72), while the reliabilities of the remaining factors were relatively low (Cronbach's alpha=0.53-0.61). The eight factors were then validated against the guide dog school's own criteria for rejecting dogs for behavioral reasons. The results of this analysis confirmed the construct validity of the puppy raisers' questionnaire assessments of their dogs, and suggested that such methods can provide a useful and accurate means of predicting the suitability of dogs for guiding work. Various modifications to the original questionnaire are proposed in order to enhance its overall reliability.

Factors predicting local recurrence of desmoid tumours including proliferating cell nuclear antigen.

BACKGROUND: A series of 24 patients with desmoid tumours were studied to determine factors predicting local recurrence, and to establish whether these desmoid tumours were oestrogen receptor-positive or -negative. METHODS: Histology was reviewed and immunohistochemical studies were undertaken. Risk factors for local recurrence were analysed. RESULTS: The findings indicate that the 24 desmoid tumours were oestrogen receptor- and progesterone receptor-negative. Most tumours were proliferating cell nuclear antigen (PCNA)-positive, and positivity was graded by percentage of cells staining and the intensity of the staining. The presence of incomplete macroscopic or histological surgical resection margins did not correlate with local recurrence. Although all tumours that recurred were strongly PCNA-positive with a high percentage of positive cell staining, this trend was not significant. Local recurrence was more common in desmoid tumours arising in extra-abdominal sites (P = 0.03). Extra-abdominal desmoid tumours were significantly more likely to have incomplete histological margins following resection (P < 0.05). CONCLUSION: Desmoid tumours are oestrogen receptor- and progesterone receptor-negative. Of factors analysed for local recurrence, only the extra-abdominal site was significant.

Evaluation of clomipramine as an adjunct to behavioural therapy in the treatment of separation-related problems in dogs.

Forty-nine dogs showing signs of separation-related problems were randomly assigned to one of three groups: group A (15 dogs) received a placebo twice daily; group B (17 dogs) received clomipramine at 0.5 to 1.0 mg/kg twice daily; and group C (17 dogs) received clomipramine at 1.0 to 2.0 mg/kg twice daily. All the dogs also received behavioural therapy. Their owners were required to complete questionnaires about their dog's behaviour initially, and one, four and eight weeks after the treatment with clomipramine began. Bipolar ratings scales were used to monitor the frequencies of 'general', 'attachment-related' and 'separation-related' behaviours. Kruskal-Wallis tests and Kendall Rank correlations were used to determine any initial differences between the treatment groups, and the association between the initial scores and behavioural changes after one week of treatment with clomipramine. Extended Mantel-Haenszel statistics were used to evaluate the effects of clomipramine treatment versus the placebo, and Page's test was used to assess the effectiveness of behavioural therapy on its own. There were no significant differences in the demographic characteristics of the owners of the dogs assigned to the three groups. The dogs differed slightly in age between groups, and the dogs in the two clomipramine-treated groups were reported as showing problems at a significantly earlier age than those in the placebo group. Clomipramine treatment had a sustained suppressive effect on the dogs' general activity levels, and a more modest suppressive effect on their attachment-related tendency to want much physical contact with their owners. The typical signs of separation-related behaviour problems were not significantly affected by treatment with clomipramine, but behavioural therapy on its own was highly effective in reducing behavioural problems.

Pre-operative core biopsy of soft-tissue tumours facilitates their surgical management.

BACKGROUND: Soft-tissue sarcomas are rare, and clinical differentiation of benign tumours from sarcomas is sometimes impossible. Further, the diagnosis of soft-tissue sarcomas may be unsuspected pre-operatively, and the presenting mass enucleated. While enucleation (excisional biopsy) is acceptable for benign lesions, it is inappropriate for sarcomas, because the opportunity for the most effective management resulting in both adequate local control and functional limb salvage surgery is compromised. A high rate of wound complications following open incisional biopsy may also compromise local treatment. Inappropriate siting of the incision for both incisional and excisional biopsies may adversely affect subsequent surgery and radiotherapy. METHODS: We therefore assessed the accuracy of core biopsy in the diagnosis of soft-tissue tumours, and planning of definitive surgery. All patients with primary soft-tissue tumours managed by two surgeons with a special interest in soft-tissue sarcomas since 1991 were reviewed. More than half (53%) were referred from other specialists. RESULTS: Of 45 cases, 37 (82%) were referred with the tumour intact, and of these 31 (84%) underwent core biopsy. The overall accuracy of core biopsy was 84%. The sensitivity was 94%, with 100% specificity. In most patients this allowed planning of definitive one-stage surgery (P < 0.005). Of the remaining five non-diagnostic cores, four were benign and one was a non-specific malignancy. CONCLUSIONS: Core biopsy has a high degree of accuracy in the diagnosis of soft-tissue tumours, particularly malignant lesions, and is not misleading. Core biopsy avoids the complications of open biopsy, and enables planning of one-stage surgery when used in combination with appropriate imaging.

Cosmesis following complete local excision of breast cancer.

BACKGROUND: With the establishment of the safety of breast conservation in early breast cancer, cosmesis has become an increasingly important end-point of treatment. The aim of the present study was to establish a model to assess breast cosmesis after complete local excision and to assess cosmesis achieved in patients who had surgery using the seroma technique. METHODS: A total of 42 patients were retrospectively reviewed and assessed by independent clinical assessment by a surgeon, structured questionnaire and clinical photography. RESULTS: A total of 86% of patients were rated by surgeon and patient as having a good or excellent cosmetic outcome. There was a high degree of concordance between independent clinical assessment and clinical photographic analysis. CONCLUSIONS: A model has been established for the assessment of breast cosmesis; the technique of seroma formation without reconstruction of the defect results in good or excellent cosmesis in the majority of patients.

Aggressive behaviour in English cocker spaniels and the personality of their owners.

The aim of the study was to determine whether there is an association between the personality of the owners of English cocker spaniels and the expression of aggressive behaviour by their dogs. Two-hundred-and-eighty-five owners of purebred English cocker spaniels completed the Catell 16 Personality Questionnaire. One-hundred-and-twenty-eight of them owned 153 dogs previously classified as being 'low' in terms of aggressiveness and 157 owned 172 dogs classified as being 'high' in terms of aggressiveness. Both groups of owners were similar in terms of a variety of demographic variables, including the number of adults and children in the household, the type of house and the sex of the owner. The dogs in both groups were similar in age, age when acquired and sex ratio. Analyses of the data using unpaired t-tests revealed that the owners of high aggression dogs were significantly more likely to be tense (P < 0.001), emotionally less stable (P < 0.01), shy (P < 0.01) and undisciplined (P < 0.05) than owners of low aggression dogs.

Pre-operative histological diagnosis of breast cancer.

BACKGROUND: A concordant triple assessment (clinical, mammographic and cytological) diagnosis of breast malignancy allows for pre-operative planning of surgery and may also allow for one-stage surgery. However, while the accuracy of cytology is high, it is unable to distinguish invasive cancer from ductal carcinoma in situ (DCIS). A malignant mass may be due to pure in situ cancer and hence axillary dissection may be avoided if pre-operative histology is available. METHODS: A consecutive series of 300 cases of breast cancer treated over the last 5 years by the two authors was analysed to determine: the method of achieving pre-definitive operation histology; the number of stages of surgery required; and the number of cases of mass-forming DCIS which could be susceptible to over-treatment. RESULTS: Of 289 patients undergoing local definitive surgery for breast cancer, 12 (42%) had clinical masses predominantly due to DCIS and in most of these patients axillary dissection was avoided. Histology was obtained prior to definitive surgery in 272 (94.1%) patients, by intra-operative frozen section in 159 (55.0%), incisional biopsy in 37 (12.8%), needle localization biopsy in 62 (21.5%) and core biopsy in 14 (4.8%). A total of 189 patients (65.4%) underwent one-stage surgery only. Breast conservation was achieved in 210 (72.7%) patients. Those requiring mastectomy were significantly more likely to have required two stages of surgery as were those with lesions detected by screening. CONCLUSIONS: Mass-forming DCIS cannot be predicted pre-operatively by triple assessment alone; and therefore pre-operative histology is required to avoid axillary dissection. Pre-operative histology may be obtained by core biopsy or intra-operative frozen section to identify DCIS and distinguish it from invasive disease, but both allow a one-stage surgical procedure in the majority of cases.

Phlegmonous enteritis: an unusual cause of abdominal pain.

Phlegmonous enteritis is a rare infective inflammatory condition of the gut which is difficult to diagnose and which is often fatal. Although first described more than 150 years ago, very few cases have subsequently appeared in the literature. In this case the diagnosis of atypical small intestinal pathology was suggested by unusual CT findings. Coupled with the clinical picture, this prompted laparotomy which in turn confirmed the diagnosis of phlegmonous enteritis. A literature review discusses the epidemiology, predisposing conditions, postulated aetiologies and treatment.

Modification of growth of desmoid tumours in tissue culture by anti-oestrogenic substances: a preliminary report.

BACKGROUND: Tamoxifen and toremifene have been used in patients with advanced desmoid tumours with response rates of 51%. METHODS: We developed an experimental model of desmoid tumour cells in tissue culture to study their effect. Four cell lines were established in tissue culture. All native and corresponding cultured tumours were oestrogen receptor negative. Tumour 1 was from a 22 year old with familial adenomatous polyposis (FAP) and recurrent abdominal wall desmoid tumours. She remains disease free on tamoxifen 4 years following surgery. Both her mother and sister also have shown regression of their FAP-associated desmoid tumours at the menopause and on tamoxifen, respectively. We assessed the effect of tamoxifen on desmoid tumours in tissue culture at 780 ng/mL. The results were assessed by cell density counting. RESULTS: Tumours 1 and 2 have responded with an approximately. 50% reduction in growth to tamoxifen at 780 ng/mL. CONCLUSIONS: This apparent growth inhibitory effect of tamoxifen on two desmoid tumour cell lines appears to be independent of oestrogen and correlates with the in vivo effect of tamoxifen on three desmoid tumours in an FAP family.